MX2008008135A

MX2008008135A - Chemical compounds

Info

Publication number: MX2008008135A
Application number: MXMX/A/2008/008135A
Authority: MX
Inventors: Lyne Paul; Scott David; Ioannidis Stephanos; Zheng Xiaolan; Aquila Brian; Cook Donald; Dakin Leslie
Original assignee: Aquila Brian; Astrazeneca Ab; Astrazeneca Uk Limited; Cook Donald; Dakin Leslie; Ioannidis Stephanos; Lyne Paul; Scott David; Zheng Xiaolan
Priority date: 2005-12-22
Filing date: 2008-06-20
Publication date: 2008-09-26

Abstract

The invention relates to chemical compounds, or pharmaceutically acceptable salts thereof of the formula which possess CSF 1R kinase inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.

Description

CHEMICAL COMPOUNDS BACKGROUND OF THE INVENTION The invention relates to chemical compounds, or pharmaceutically acceptable salts thereof, which possess factor kinase receptor (CSF-1R) inhibitory activity that stimulates the colony and are therefore useful for their anticancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of chemical compounds, to pharmaceutical compositions containing them and their use in the manufacture of medicaments for use in the production of an anticancer effect in a warm-blooded animal such as man. Tyrosine receptor kinases (RTKs) are a sub-family of protein kinases that play a critical role in cell signaling and are involved in a variety of cancer-related processes including proliferation, survival, angiogenesis , invasion and cell metastasis. They are considered to be at least 96 different RTK's including CSF-1R. CSF-1R or c-fms is originally identified as the oncogenic v-fms of the feline sarcoma virus. CSF-1R is a member of the class III RTKs together with c-Kit, tyrosine kinase 3 related to fms (Flt3) and a and ß of the platelet-derived growth factor receptor (PDGFRa and PDGFRβ for its acronym in English ). All these kinases have been involved in the process of tumorigenesis. CSF-1R is normally expressed as an immature 130 kDa transmembrane protein and ultimately results in a mature 145-160 kDa N-linked glycosylated cell surface protein. The macrophage colony stimulation factor (M-CSF or CSF-1), the ligand for CSF-1R, bound to the receptor results in dimerization, self-phosphorylation of the receptor and subsequent activation of the transduction cascades of the downstream signal (CJ Sherr, Biochim Biophys Acta, 1988, 948: 225-243). CSF-1R is normally expressed in myeloid cells of the phagocytic mononuclear lineage and their progenitors of bone marrow as well as the epithelial cells of the ducts and alveoli during lactation, but without normal rest, breast tissue. The activation of CSF-1R stimulates the proliferation, survival, motility and differentiation of cells of the monocyte / macrophage lineage. Mature macrophage plays a key role in the development of normal tissue and immune defense (F.L. Pixley and E.R. Stanley, Trends in Cell Biology, 2004, 14 (11): 628-638). For example, osteoblasts secrete CSF-1 and activate the receptor in osteoclastic progenitors resulting in differentiation into mature osteoclasts (S.L. Teitelbaum, Science, 2000, 289: 1504-1508). The axis of CSF-1R plays an important role in the placental development, embryonic implantation, ductal of the mammary gland and lobuloalveolar development (E. Sapi, Exp Biol Med, 2004, 229: 1-11). Transfection of CSF-1R with or without CSF-1 induces the in vivo transformation and tumorigenicity of NIH3T3 (Rat2 and ovarian granulosa cells.) The autocrine and / or paracrine signaling mechanisms have been involved in the activation of CSF-1R in the tumor epithelium and tumor-associated macrophage Abnormal expression and activation of CSF-1R and / or its ligand have been found in human myeloid leukemia, prostate, breast, ovarian, endometrial and a variety of other cancers. have demonstrated that overexpression of CSF-1R is associated with poor prognosis in several of these cancers.In addition, the axis of CSF-1 / CSF-1R plays a key role in tumor-associated macrophage regulation, which have been postulated to play a significant role in tumor angiogenesis, invasion and progression, (E. Sapi, Exp Biol Med, 2004, 229: 1-11) Brief Description of the Invention Accordingly, the present invention provides a c ompuesto of formula (I): (I) or an acceptable pharmaceutical salt thereof; where: A is wherein Ring A is aryl, heteroaryl, carbocyclyl or heterocyclyl; wherein if the heterocyclyl contains an -NH- moiety the nitrogen may optionally be substituted by a group selected from R5; or A is alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, or alkynyl of 2 to 6 carbon atoms, each of which can optionally be substituted with 1, 2, or 3 substituents selected from aryl , heteroaryl, halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms , N- (alkyl of 1 to 6 carbon atoms) amino, N, N- (alkyl of 1 to 6 carbon atoms) 2-amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbon) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-carbamoyl, alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, alkoxycarbonylamino from 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-sulfamoyl, N- (alkyl of 1 to 6 carbon atoms) o) -N- (alkoxy of 1 to 6 carbon atoms) sulfamoyl, N, N '- (alkyl of 1 to 6 carbon atoms) 2ureido, N- (alkyl of 1 to 6 carbon atoms) -N', N '- (alkyl of 1 to 6 carbon atoms) 2ureido, alkylsulfonylamino of 1 to 6 carbon atoms, carbocyclyl-R6- or heterocyclyl-R7-; wherein A can optionally be substituted on the carbon by one or more R8; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen may optionally be substituted by a group selected from R9; R1 is a substituent on carbon and is selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N , N- (alkyl of 1 to 6 carbon atoms) 2amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) carbon) 2-carbamoyl, alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, alkoxycarbonylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-sulfamoyl, N- (alkyl of 1 to 6 carbon atoms) -N- (alkoxy of 1 to 6 carbon atoms) sulfamoyl, N , N '- (alkyl from 1 to 6 carbon atoms) 2ureido, N ', N' - (alkyl of 1 to 6 carbon atoms) 2ureido, N- (alkyl of 1 to 6 carbon atoms) -N'N '- (alkyl of 1 to 6 carbon atoms) carbon) 2ureido, alkylsulfonylamino of 1 to 6 carbon atoms, carbocyclyl-R6- or heterocyclyl-R7-; wherein R1 can optionally be substituted on the carbon by one or more R8; and wherein if the heterocyclyl contains a -NH- moiety the nitrogen can optionally be substituted by a group selected from R9; n is selected from 0-4; wherein the values of R1 may be the same or different; X is absent or is O or NRa, where Ra is H or alkyl of 1 to 6 carbon atoms; R2 and R3 are independently selected from hydrogen, halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N, N - (alkyl of 1 to 6 carbon atoms) 2-amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-carbamoyl, alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N- ( alkyl of 1 to 6 carbon atoms) 2-sulfamoyl, alkylsulfonylamino of 1 to 6 carbon atoms, carbocyclyl-R 10- or heterocyclyl-R-; wherein R2 can optionally be substituted on the carbon by one or more R12; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen can optionally be replaced by a selected group of R 3; R 4 is selected from halo, cyano, amino, carboxy, carbamoyl, mercapto, sulfamoyl, ureido, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N, N- (alkyl of 1 to 6 carbon atoms) carbon) 2-amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2carbamoyl, alkyl of 1 to 6 carbon atoms carbonS (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-sulphamoyl, alkylsulfonylamino of 1 to 6 carbon atoms, carbocyclyl-R14- or heterocyclyl-R15-; wherein R4 may optionally be substituted on the carbon by one or more R16; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen can optionally be replaced by a group selected from R17; m is selected from 0-2; wherein the values of R4 may be the same or different; R8 and R12 are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N, N- ( alkyl of 1 to 6 carbon atoms) 2 amino, N- (alkyl of 1 to 6 carbon atoms) -N- (alkoxy of 1 to 6 carbon atoms) amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2carbamoyl, alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-sulfamoyl, alkylsulfonylamino of 1 to 6 carbon atoms, carbocyclyl-R18- or heterocyclic- R19-; wherein R8 and R12 independently of each other may optionally be substituted on the carbon with one or more R20; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen can optionally be replaced by a group selected from R21; R16 is selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms , alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N, N- (alkyl of 1 to 6 carbon atoms) 2-amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2carbamoyl, alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-sulfamoyl, alkylsulfonylamino of 1 to 6 carbon atoms, carbocyclyl-R22- or heterocyclyl-R23-; wherein R1 can optionally be substituted on the carbon by one or more R24; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen can optionally be substituted by a group selected from R25; R6, R7, R10, R11, R14, R15, R18, R19, R22 and R23 are independently selected from a direct bond, "-O-, -N (R26) -, -C (O) -, -N (R27) ) C (O) -, -C (O) N (R28) -, -S (O) 8-, -SO2N (R29) -o -N (R30) SO2-; wherein R26, R27, R28, R29 and R30 are independently selected from hydrogen or alkyl of 1 to 6 carbon atoms and s is 0-2; R5, R9, R13, R17, R21 and R25 are independently selected from alkyl of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkylsulfonyl of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms , carbamoyl, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsulfonyl; R20 and R24 are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N -methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N, N-dimethylcarbamoyl, N, N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, phenyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethyl sulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulphamoyl, N, N-dimethylsulphamoyl, N, N-diethylsulphamoyl or N-methyl-N-ethylsulphamoyl. In another aspect, the invention relates to compounds of formula (I), wherein: A is wherein Ring A is aryl, heteroaryl, carbocyclyl or heterocyclyl; wherein if the heteroaryl or heterocyclyl contains an -NH- moiety the nitrogen may optionally be substituted by a group selected from R5; A is alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, or alkynyl of 2 to 6 carbon atoms; wherein A can optionally be substituted on the carbon by one or more R8a; and wherein if the heterocyclyl contains a -NH- moiety the nitrogen may optionally be substituted by a group selected from R9a; R1 is a substituent on carbon and is selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl from 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N , N- (alkyl of 1 to 6 carbon atoms) 2amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) carbon) 2-carbamoyl, alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, alkoxycarbonylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-sulfamoyl, N- (alkyl of 1 to 6 carbon atoms) -N- (alkoxy of 1 to 6 carbon atoms) sulfamoyl, N , N '- (alkyl of 1 to 6 carbon atoms) 2ureido, N ', N' - (alkyl of 1 to 6 carbon atoms) 2ureido, N- (alkyl of 1 to 6 carbon atoms) -N ', N' - (alkyl of 1 to 6 carbon atoms) 2ureido, alkylsulfonylamino of 1 to 6 carbon atoms, carbocyclyl-R6- or heterocyclyl-R7-; where R1 can optionally be substituted on the carbon by one 0 more R8; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen may optionally be substituted by a group selected from R9; n is selected from 0-4; wherein the values of R may be the same or different; X is absent or is O or NRa, where Ra is H or alkyl of 1 to 6 carbon atoms; R2 and R3 are independently selected from hydrogen, halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N, N- (alkyl of 1 to 6 carbon atoms) 2-amino, alkanoylamino of 1 to 6 carbon atoms, N, N- (alkyl) 1 to 6 carbon atoms) 2carbamoyl, alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms ) sulfamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-sulfamoyl, alkylsulfonylamino of 1 to 6 carbon atoms, carbocyclyl-R10- or heterocyclyl-R1 -; wherein R2 can optionally be substituted on the carbon by one or more R12; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen may optionally be substituted by a group selected from R13; R 4 is selected from halo, cyano, amino, carboxy, carbamoyl, mercapto, sulfamoyl, ureido, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N, N- (alkyl of 1 to 6 carbon atoms) carbon) 2-amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2carbamoyl, N- (alkyl of 1 to 6 carbon atoms) -N- (alkoxy of 1 to 6 carbon atoms) carbamoyl, alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, N - (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-sulfamoyl, alkylsulfonylamino alkyl of 1 to 6 carbon atoms, carbocyclyl-R 14- or heterocyclyl-R 15-; wherein R 4 can optionally be substituted on the carbon by one or more R 1; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen can optionally be replaced by a group selected from R17; m is selected from 0-2; wherein the values of R4 may be the same or different; R8, R8a, and R2 in each case are independently selected from aryl, heteroaryl, halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N, N- (alkyl of 1 to 6 carbon atoms) 2 amino, N- (alkyl of 1 to 6 carbon atoms) -N- (alkoxy of 1 to 6 carbon atoms) amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (to the chyle of 1 to 6 carbon atoms) 2carbamoyl, alkyl of 1 to 6 carbon atoms (O ) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, alkoxycarbonylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N- (alkyl of 1) to 6 carbon atoms) -N - (C 1 -C 6 -alkoxy) sulfamoyl, N, N '- (C 1 -C 6 -alkyl) 2-sulfamoyl, N, N' - (C 1 -C 6 -alkyl) 2-halide, N ' , N '- (alkyl of 1 to 6 carbon atoms) 2ureido, N- (alkyl of 1 to 6 carbon atoms) -N', N '- (alkyl of 1 to 6 carbon atoms) 2ureido, alkylsulfonylamino of 1 to 6 carbon atoms, carbocyclyl-R18- or heterocyclyl-R19-; wherein R8, R8a, and R12 independently of each other may optionally be substituted on the carbon with one or more R20; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen can optionally be replaced by a group selected from R21; R6 in each case is independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N, N- (alkyl of 1 to 6 carbon atoms) 2-amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2carbamoyl , alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N '- ( alkyl of 1 to 6 carbon atoms) 2-sulfamoyl, alkylsulfonylamino of 1 to 6 carbon atoms, carbocyclyl-R22- or heterocyclyl-R23-; wherein R16 can optionally be substituted on the carbon by one or more R24; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen can optionally be substituted by a group selected from R25; R6, R7, R10, R1, R14, R15, R18, R19, R22 and R23 in each case are independently selected from a direct bond, -O-, -N (R26) -, -C (O) -, -N (R27) C (O) -, -C (O) N (R28) -, -S (O) 8-, -SO2N (R29) - 0 -N (R30) SO2-; wherein R26, R27, R28, R29 and R30 are independently selected from hydrogen or alkyl of 1 to 6 carbon atoms and s is 0-2; R5, R9, R9a, R13, R17, R21 and R25 in each case are independently selected from alkyl of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkylsulfonyl of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms, carbamoyl, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsulfonyl; R20 and R2 in each case are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, cyclopropyl, cyclobutyl, cyclopentyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N, N-dimethylcarbamoyl, N, N-dimethylcarbamoyl, N-methyl-N-ethylcarbamoyl, phenyl, methylthio, ethylthio, methylsulphinyl, sulfuryl, mesyl, ethylsulphonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulphamoyl, N-ethylsulphamoyl, N, N-dimethylsulphamoyl, N, N-diethylsulphamoyl or N-methyl-N-ethylsulphamoyl ester; wherein R20 and R24 can optionally be substituted on the carbon by one or more R50; and R50 in each case is independently selected from halo, hydroxy, cyano, and alkoxy of 1 to 6 carbon atoms. The particular values of the variable groups contained in the formula (I) are as follows. Such values may be used where appropriate with any of the definitions, claims, or modalities defined herein or hereinbelow.

A is; wherein Ring A is selected from aryl, heteroaryl, and carbocyclyl; wherein if the heteropole contains a -NH- portion the nitrogen may optionally be substituted by a selected group of R5; or A is alkyl of 1 to 6 carbon atoms; wherein A can optionally be substituted on the carbon by one or more R8a; R5 is alkyl of 1 to 6 carbon atoms; R8a in each case is independently selected from halo, alkoxy of 1 to 6 carbon atoms, and carbocyclyl-R18-, wherein R8A can optionally be substituted on carbon by one or more R20; R 8 is a direct link; and R20 is methyl.

A is; | wherein Ring A is selected from phenyl, pyridinyl, cyclopentyl, cyclohexyl, and 1 H-pyrazolyl, wherein if 1 H-pyrazolyl contains an -NH- portion the nitrogen can optionally be replaced by a group selected from R5; or A is selected from ethyl, butyl, 3-methylpentyl, 2-methylbutyl, 3-methylbutyl, sec-butoxymethyl, 2-methylprop-2-yl, but-2-yl, hex-2-yl; wherein methyl, butyl, 3-methylpentyl, 2-methylbutyl, 3-methylbutyl, sec-butoxymethyl, 2-methylprop-2-yl, but-2-yl, and hex-2-yl can optionally be substituted on carbon by one or more R8a; R5 in each case is independently selected from methyl, 2-methylprop-2-yl, and prop-2-yl; R8a in each case is independently selected from fluoro, 1-methyl-propoxy, cyclopropyl-R18-, cyclopentyl-R8-, and cyclohexyl-R18-; wherein 1-methyl-propoxy, cyclopropyl-R18-, cyclopentyl-R18-, and c? clohex? -R18- can optionally be substituted on the carbon by one or more R20, R18 is a direct bond, and R20 is methyl A is selected from 3- (1-c? ano-1-met? let? l) phenol, 3- (tr? fluoromet? l) phenol, 3-chlorophenol, 3,5-d? met ? lphene, 3-fluoro-5- (tr? fluoromet? l) phenol, 3-chloro-5-fluorophenol, 3-c? cloprop? l-5-fluorophenyl, 3,4-d? chlorophenol, 3-c? clopropylene, 3-methyl?, 3-methylcyclohexyl, 2,6-d? chlorop? r? d? n? 4-? lo, cyclopentyl, 3,4 -dimethylphenyl, 6-met? lp? r? d? n? 2-? lo, 3-chlorop? r? d? n? 4-? lo, 5-met? lp? r? d? n-3-? what, 1,5-d? met? l-1H-p? razol-3-? lo, 5-met? l-1H-p? razol-3-? What is 4-meth? lc? clohexyl, 3- (tr? fluoromet? l) c? clohexyl, 4,4-difluorocyclohexyl, 1-tert-butyl-5-met? l-1 Hp? razol-3-? lo, 1-? soprop? l-1 Hp? razol-3-? lo, butyl, 3-methylpentyl, 2-methyl butyl, 3-methylbutyl, sec-butoxymethyl, cyclohexylmethyl, 2-met? lprop-2-? lo, (4-met? Lc? Clohex?) Met? Lo, but-2-? Lo, hex-2-? Lo, cyclopropylmethyl, cyclopentylmethyl, and c? Clohex? L (d? Fluoro) met? Lo Ring A is selected from aplo, heterolalk, and carbocyclic, wherein if the heteropole contains an NH-portion the nitrogen can optionally be replaced by a group selected from R5, and R5 is alkyl of 1 to 6 carbon atoms Ring A is selected from phenyl, pipd inyl, cyclopentyl, cyclohexyl, and 1 H-pyrazolyl, wherein if 1 H-pyrazole contains an NH-portion the nitrogen can optionally be replaced by a group selected from R 5; and R5 in each case is independently selected from methyl, 2-methylprop-2-yl, and prop-2-yl. Ring A is selected from 3- (1-cyano-1-methylethyl) phenyl, 3- (trifluoromethyl) phenyl, 3-chlorophenyl, 3,5-dimethylphenyl, 3-fluoro-5- (trifluoromethyl) phenyl, 3-chloro -5-fluorophenyl, 3-cyclopropyl-5-fluorophenyl, 3,4-dichlorophenyl, 3-cyclopropylphenyl, 3-methylphenyl, 3-methylcyclohexyl, 2,6-dichloropyridin-4-yl, cyclopentyl, 3,4-dimethylphenyl, -methylpyridin-2-yl, 3-chloropyridin-4-yl, 5-methylpyridin-3-yl, 1,5-dimethyl-1 H -pyrazol-3-yl, 5-methyl-1 H -pyrazole- 3-yl, 4-methylcycloclohexyl, 3- (trifluoromethyl) cyclohexyl, 4,4-difluorocyclohexyl, 1-tert-butyl-5-methyl-1 H-pyrazol-3-yl, and 1-isopropyl-1 H- pyrazol-3-yl. A is selected from alkyl of 1 to 6 carbon atoms; wherein the alkyl of 1 to 6 carbon atoms can optionally be substituted on the carbon with one or more R8a; R8a in each case is independently selected from halo, alkoxy of 1 to 6 carbon atoms, and carbocyclyl-R18-, wherein R8A can optionally be substituted on carbon by one or more R20; R18 is a direct link; and R20 is methyl. A is selected from methyl, butyl, 3-methylpentyl, 2-methylbutyl, 3-methylbutyl, sec-butoxymethyl, 2-methylprop-2-yl, but-2-yl, hex-2-yl; wherein methyl, butyl, 3-methylpentyl, 2-methylbutyl, 3-methylbutyl, sec-butoxymethyl, 2-methylprop-2-yl, but-2-yl, and hex-2-yl can optionally be substituted on the carbon by one or more R8a; R8a in each case is independently selected from fluoro, 1-methyl-propoxy, cyclopropyl-R18-, cyclopentyl-R8-, and cyclohexyl-R18-; wherein 1-methyl-propoxy, cyclopropyl-R18-, cyclopentyl-R18-, and cyclohexyl-R18- can optionally be substituted on the carbon by one or more R20; R 8 is a direct link; and R20 is methyl. A is selected from butyl, 3-methylpentyl, 2-methylbutyl, 3-methylbutyl, sec-butoxymethyl, cyclohexylmethyl, 2-methylprop-2-yl, (4-methylcyclohexyl) methyl, but-2-yl, hex-2-yl , cyclopropylmethyl, cyclopentylmethyl, and cyclohexyl (difluoro) methyl. X is absent or is O. X is absent. X is O. R1 is a substituent on carbon and is selected from halo, alkyl of 1 to 6 carbon atoms, and carbocyclyl-R6-; wherein R1 can optionally be substituted on the carbon by one or more R8; R6 is a direct link; and R8 in each case is independently selected from halo and cyano. R1 is a substituent on carbon and is selected from fluoro, chloro, methyl, isopropyl, and cyclopropyl-R6-; wherein R1 can optionally be substituted on the carbon by one or more R8; R6 is a direct link; and R8 in each case is independently selected from fluoro and cyano. R1 is a substituent on carbon and is selected from fluoro, chloro, methyl, trifluoromethyl, 2-cyanoprop-2-yl, and cyclopropyl. R2 is hydrogen. R2 and R3 are independently selected from hydrogen, halo, alkyl of 1 to 6 carbon atoms. R2 and R3 are independently selected from hydrogen, chlorine, and methyl. R2 is hydrogen and R3 is selected from halo and alkyl of 1 to 6 carbon atoms. R2 is hydrogen and R3 is selected from chlorine and methyl. R3 is selected from halo and alkyl of 1 to 6 carbon atoms. R3 is selected from chlorine and methyl. R3 is chlorine. R3 is methyl. R4 is selected from alkyl of 1 to 6 carbon atoms, N- (C 1-6 -alkyl) carbamoyl, N- (C 1-6 -alkyl) -N- (C 1-6 -alkoxy) carbamoyl, carbocyclyl-R 14- and heterocyclyl-R 5 -; wherein R can optionally be substituted on the carbon by one or more R16; R14 is a direct link; R15 is-C (O) -; R16 in each case is independently selected from hydroxy, N- (alkyl of 1 to 6 carbon atoms) amine, N, N- (alkyl of 1 to 6 carbon atoms) 2-amino, carbocyclyl-R22- and heterocyclyl-R23-; wherein R16 can optionally be substituted on the carbon by one or more R24; and wherein if the heterocyclyl contains an NH-portion the nitrogen can optionally be substituted by a group selected from R25; R22 is -N (R26) -; R23 is a direct link; R24 in each case is independently selected from methyl, methoxy, dimethylamino, and cyclopropyl, wherein R24 may optionally be substituted on the carbon by one or more R50; R25 is alkyl of 1 to 6 carbon atoms; R26 is hydrogen; and R50 is hydroxy. R4 is selected from methyl, isopropyl, N-methylcarbamoyl, N-methyl-N-methoxycarbamoyl, cyclopropyl-R14-, and morpholino-R15-; wherein R 4 can optionally be substituted on the carbon by one or more R 6; R1 is a direct link; R15 is-C (O) -; R16 in each case is independently selected from hydroxy, methylamino, ethylamine, dimethylamino, N-methyl-N-ethylamine, azetidin-1-yl, morpholino, piperazin-1-yl, picperidin-1 -lo, cyclobutyl-R22-, and cyclopropyl-R22-; wherein R16 can optionally be substituted on the carbon by one or more R24; and wherein the piperazin-1-yl can optionally be substituted on nitrogen by a group selected from R25; R22 is -N (R26) -; wherein R26 is hydrogen; R24 in each case is independently selected from methoxy, dimethylamino, cyclopropyl, cyclobutyl, and cyclopropyl, wherein R24 may optionally be substituted on the carbon with one or more R50; R25 is methyl; and R50 is hydroxy. R4 is selected from methyl, isopropyl, N-methylcarbamoyl, (4-methylpiperazin-1-yl) methylmorpholinecarbonyl, N-methyl-N-methoxycarbamoyl, hydroxymethyl, (dimethylamino) methyl, 1-hydroxyethyl, piperidinmethyl, (methylamino) methyl , morpholin-4-ylmethyl, 2- (dimethylamino) ethyl, 1-azetidinylmethyl, (cyclobutylamino) methyl, [(cyclopropylmethyl) amino] methyl, [(2-methoxyethyl) methylamino] methyl, [4- (hydroxymethyl) piperidin-1-yl] methyl, isopropyl, (cyclopropylamino) methyl, and cyclopropyl. m is selected from 0 to 2, where the values of R4 can be the same or different, m is selected from 0 and 1. m is. m is 0. n is selected from 0 to 2, where the values of R may be the same or different. n is 2, wherein the values of R1 may be the same or different. n is selected from 1 and 2, where the values of R1 can be the same or different. n is 1. n is 0. In a further aspect of the invention, a compound of formula (I) (as described hereinabove) is provided herein wherein: A is is selected from aryl, heteroaryl, and carbocyclyl; wherein if the heteropole contains a -NH- portion the nitrogen may optionally be substituted by a selected group of R5; or A is alkyl of 1 to 6 carbon atoms; wherein A can optionally be substituted on the carbon by one or more R8a; X is absent or is O; R1 is a substituent on carbon and is selected from halo, alkyl of 1 to 6 carbon atoms, and carbocyclyl-R6-; wherein R1 can optionally be substituted on the carbon by one or more R8; R2 and R3 are independently selected from hydrogen, halo, alkyl of 1 to 6 carbon atoms; R 4 is selected from alkyl of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl-, N- (alkyl of 1 to 6 carbon atoms) -N- (alkoxy of 1 to 6 atoms) carbon) carbamoyl, carbocyclyl-R14, and heterocyclyl-R5; wherein R4 may optionally be substituted on the carbon by one or more R16; R5 is alkyl of 1 to 6 carbon atoms; R6 is a direct link; R8 in each case is independently selected from halo and cyano; R8a in each case is independently selected from halo, alkoxy of 1 to 6 carbon atoms, and carbocyclyl-R18-, wherein R8a may optionally be substituted on carbon by one or more R20; R14 is a direct link; R15 is -C (O) -; R16 in each case is independently selected from hydroxy, N- (alkyl of 1 to 6 carbon atoms) amino, N, N- (alkyl of 1 to 6 carbon atoms) 2-amino, carbocyclyl-R22- and heterocyclyl-R23-; wherein R16 can optionally be substituted on the carbon by one or more R2; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen can optionally be substituted by a group selected from R25; R18 is a direct link; R20 is methyl; R22 is -N (R26) -; R23 is a direct link; R24 in each case is independently selected from methyl, methoxy, dimethylamino, and cyclopropyl, wherein R24 may optionally be substituted on the carbon by one or more R50; R25 is alkyl of 1 to 6 carbon atoms; R26 is hydrogen; R50 is hydroxy; m is selected from 0 to 2, wherein the values of R4 may be the same or different; and n is selected from 0 to 2, wherein the values of R1 may be the same or different.

A is selected from A is where Ring A is selected from phenyl, pyridinyl, cyclopentyl, cyclohexyl, and 1 H-pyrazolyl, wherein if 1 H-pyrazolyl contains a -NH- portion the nitrogen can optionally be replaced by a group selected from R5; or A is selected from ethyl, butyl, 3-methylpentyl, 2-methylbutyl, 3-methylbutyl, sec-butoxymethyl 2-methylprop-2-yl, but-2-yl, and hex-2-yl; wherein methyl, butyl, 3-methylpentyl, 2-methylbutyl, 3-methylbutyl, sec-butoxymethyl, 2-methylprop-2-yl, but-2-yl, and hex-2-yl can optionally be substituted on carbon by one or more R8a; X is absent or is O; R1 is a substituent on carbon and is selected from fluoro, chloro, methyl, isopropyl, and cyclopropyl-R6-; wherein R1 can optionally be substituted on the carbon by one or more R8; R2 and R3 are independently selected from hydrogen, chlorine, and methyl; R4 is selected from methyl, isopropyl, N-methylcarbamoyl, N-methyl-N-methoxycarbamoyl, cyclopropyl-R14-, and morpholino-R15-; wherein R4 may optionally be substituted on the carbon by one or more R16; . R6 is a direct link; R5 in each case is independently selected from methyl, 2-methylprop-2-ylo, and prop-2-yl; R8 in each case is independently selected from fluoro and cyano; R8a in each case is independently selected from fluoro, 1-methyl-propoxy, cyclopropyl-R18-, cyclopentyl-R18- and cyclohexyl-R18-; wherein 1-methyl-propoxy, cyclopropyl-R18-, cyclopentyl-R18-, and cyclohexyl-R18- can optionally be substituted on the carbon by one or more R20; R 4 is a direct link; R15 is -C (O) -; R16 in each case is independently selected from hydroxy, methylamino, ethylamino, dimethylamino, N-methyl-N-ethylamino, azet? D? N-1-yl, morfolmo, p? Peraz? N-1 -lio, p? Per? d? n-1-yl, cyclobutyl-R22-, and c? cloprop? l-R22-, wherein R16 may optionally be substituted on the carbon by one or more R24, and wherein the p? peraz? n-1-yl it may be optionally substituted on nitrogen by a group selected from R25, R18 is a direct bond, R20 is methyl, R22 is -N (R26) -, where R26 is hydrogen, R24 is independently selected from methoxy, dimethylamino, cyclopropyl , cyclobutyl, and cyclopropyl, wherein R24 can optionally be substituted on the carbon by one or more R50, R25 is methyl, R50 is hydroxy, m is selected from 0 and 1, and n is selected from 0 to 2, wherein the values of R1 may be the same or different A is selected from 3- (1-c? Ano- 1 -met? Let? L) phenol, 3- (tr? Fluoromet? L) phenol, 3-chlorophenol, 3,5-d? Met? Lyl, 3-fluoro-5- ( tr? fluoromet? i) phenol, 3-chloro-5-fluorophenol, 3-c? clopropyl-5-fluorophenyl, 3,4-d? chlorophenol, 3-c? cloprop? lfen? it, 3-methylen, 3-methylcyclohexyl, 2,6-d? chlorop? r? d? n? 4-? lo, cyclopentyl, 3,4-dimethylphenyl, 6-met? lp? pd? n -2-? Lo, 3-chlorop? R? D? N? 4-? Lo, 5-m ethyl pi pd? N-3-? Lo, 1,5-d? Met? L-1H-p? Razol -3-? Lo, 5-met? L-1H-p? Razol-3-yl, 4-methylcyclohexyl, 3- (trifluoromethyl) cyclohexyl, 4,4-difluorocyclohexyl 1-tert-butyl-5-methyl-1H- pyrazol-3-yl, 1-isopropyl-1 H -pyrazol-3-yl, butyl, 3-methylpentyl, 2-methylbutyl, 3-methylbutyl, sec-butoxymethyl, cyclohexylmethyl, 2-methylprop-2-yl, (4- methylcyclohexyl) methyl, but-2-yl, hex-2-yl, cyclopropylmethyl, cyclopentylmethyl, and cyclohexyl (di-fluoro) methyl; X is absent or is O; R is a substituent on carbon and is selected from fluoro, chloro, methyl, trifluoromethyl, 2-cyanoprop-2-yl, and cyclopropyl; R2 is hydrogen; R3 is selected from chlorine and methyl; R4 is selected from methyl, isopropyl, N-methylcarbamoyl, (4-methylpiperazin-1-yl) methyl, morpholinecarbonyl, N-methyl-N-methoxycarbamoyl, hydroxymethyl, (dimethylamino) methyl, 1-hydroxy ethyl, pyperidinmethyl, (methylamino) methyl, morpholin-4-ylmethyl, 2- (dimethylamino) ethyl, 1-azetidinylmethyl, (cyclobutylamino) methyl, [(cyclopropylmethyl) amine] m ethyl, [(2-methoxyethyl) methylamino] methyl, [4- (hydroxymethyl ) piperidin-1-1] metho1, isopropyl, (cyclopropylamine) methyl, and cyclopropyl; m is selected from 0 and 1; and n is selected from 0 to 2, wherein the values of R1 may be the same or different. That is, it is also provided as a compound of formula (Ia): (Ia) or a pharmaceutically acceptable salt thereof; wherein: R1, n, X, R2, R3, R4, and m are as defined by a compound of formula (I). That is, it is also provided as a compound of formula (Ib): (ib) or a pharmaceutically acceptable salt thereof; where: A is J wherein Ring A is heteroaryl; and R1, n, X, R2, R3, R4, and m are as defined by a compound of formula (I). That is, it is also provided as a compound of formula (le): (I) or an acceptable pharmaceutical salt thereof; wherein: or a pharmaceutically acceptable salt thereof; where: < * A is, | wherein Ring A is carbocyclyl; and R, n, X, R2, R3, R4, and m are as defined by a compound of formula (I). That is, it is also provided as a compound of formula (Id): Od) or a pharmaceutically acceptable salt thereof; where: wherein Ring A is heterocyclyl; wherein if the heterocyclyl contains an -NH- moiety the nitrogen can optionally be substituted by a group selected from R5; and R1, n, X, R2, R3, R4, R5, and m are as defined by a compound of formula (I). That is, it is also provided as a compound of formula (le): (le) or a pharmaceutically acceptable salt thereof; wherein: A is alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, or alkynyl of 2 to 6 carbon atoms, each of which can optionally be substituted with 1, 2 or 3 substituents selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- ( alkyl of 1 to 6 carbon atoms) amino, N, N- (alkyl of 1 to 6 carbon atoms) 2-amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-carbamoyl, alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, alkoxycarbonylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-sulfamoyl, N- (alkyl of 1 to 6 carbon atoms) -N- ( alc oxy of 1 to 6 carbon atoms) sulfamoyl, alkylsulfonylamino of 1 to 6 carbon atoms, carbocyclyl-R6- or heterocyclyl-R7-; wherein A can optionally be substituted on the carbon by one or more R8; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen may optionally be substituted by a group selected from R9; and X, R2, R3, R4, R6"8, and m are as defined by a compound of formula (I), ie, it is also provided as a compound which is: 5- { [3- (1- cyano-1-methylethyl) benzoyl] amino.} -2-methyl-N- (2-methyl-1,3-thiazol-5-yl) benzamide; 2-chloro-N-1,3-thiazole- 5-yl-5- { [3- (trifluoromethyl) benzoyl] amino} benzamide; 2-chloro-5 - [(3-chlorobenzoyl) amino] -N-1,3-thiazole- 5-ylbenzamide; 2-chloro-5 - [(3,5-dimethylbenzoyl) amino] -N-1,3-thiazol-5-ylbenzamide; 5- { [3- (1-cyano-1- methylethyl) benzoyl] amino] -2-methyl-N-1,3-thiazole-5-methylbenzamide; 2-methyl-N- (2-methyl-1,3-thiazole-5-I) ) -5- { [3- (trifluoromethyl) benzoyl] amino.} Benzamide; 2-chloro-5 - [(3-chlorobenzoyl) amino] -N- (2-methyl-1,3-t) Azol-5-yl) benzamide; 2-chloro-5 - [(3,5-dimethylbenzoyl) amino] -N- (2-methyl-1,3-thiazol-5-yl) benzamide; 2-cl or -N- (2-methi 1-1, 3-thiazol-5-yl) -5- { [3- (trifluoromethyl) benzoyl] amino} benzamide; 2-chloro-5- { [3 -fluoro-5- (trifluoromethyl) benzoyl] amino.}. -N- (2-met? l-1,3-t? azol-5-? l) benzam ? da, 5 - [(5- { [3- (1-c? Ano-1-met? Let? L) benzo? L] am? No} -2-methyl-benzoyl-1-amino] -N-methyl-1,3-t-azole-2-carboxamide, 5-. { [3-Fluoro-5- (tr? Fluoro met? L) benzo? L] am? No} -2-met? N-N- (2-met? L-1, 3-t? Azol-5? L) benzamide, 5 - [(3-chloro-5-fluorobenzo? L) am? No] - 2-met? N- (2-met? L-1,3-t? Azol-5? L) benzamide, 5 - [(3-c? Cloprop? L-5-fluoro benzo? L) am ? no] -2-met? N- (2-met? l-1, 3-t? azol-5-? l) benzamide, 5 - [(3-chlorobenzo? l) am? no] -2 -met? lN- (2-met? l-1,3-t? azol-5-? l) benzamide, 5- [3,4-d? chlorobenzo? l) am? no] -2-met ? lN- (2-n? et? -1-1,3-t? azol-5? l) benzamide, 5 - [(3-c? cloprop? lbenzo? l) am? no] -2- met? N- (2-met? l-1,3-t? azol-5-? l) benzamide, 5 - [(3,5-d? met? lbenzo? l) am? no] -2 -met? lN- (2-met? l-1,3-t? azol-5-? l) benzamide, 2-met? l-5 - [(3-met? lbenzo? l) am? no ] -N- (2-met? L-1), 3-t-azol-5-? L) benzamide, 2,6-d? Chloro-N- (4-met? L -3 { [(2-met? L-1, 3- t? azol-5-? l) am? no] carbon? l.} fen? l)? are? cot? nam? da, 2-met? l-5-. { [(3-met? Lc? Clohex? L) carbon? L] am? No} -N- (2-met? L-1,3-tt? Azole-5? L) benzamide, 2-met? LN- (2-met? L-1,3-t? Azol-5- ?) -5- (pentane? lam?) benzamide, or 2-methyl-5 - [(4-methylhexanoyl) amino] -N- (2-methyl-1,3-thiazol-5-yl) benzamide. That is, a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable diluent or carrier is also provided. That is, a compound of formula (I), or a pharmaceutically acceptable salt thereof, is also provided for use as a medicament. That is, the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, is also provided in the manufacture of a medicament for use in the production of an inhibitory effect on the CSF-1R kinase in an animal. of warm blood like a man. That is, the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, is also provided in the manufacture of a medicament for use in the production of an anti-cancer effect in a warm-blooded animal such as a man. . That is, the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, is also provided in the manufacture of a medicament for use in the treatment of melanoma, papillary thyroid tumors, cholangiocarcinomas, colon cancer, ovarian cancer, lung cancer, leukemias, lymphoid malignancies, carcinomas and sarcomas of the liver, kidney, bladder, prostate, breast and pancreas, and primary and recurrent solid tumors of the skin, colon, thyroid, lungs and ovaries. That is, the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, is also provided in the manufacture of a medicament for use in the treatment of breast, ovarian, bladder, cervical, endometrial tumors, prostate, lung, kidney and pancreatic; hematologic malignancies including myelodysplastic syndrome, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma and chronic lymphocytic leukemia; and glioma, squamous cell carcinoma of the esophagus, malignant melanoma of the uvea and follicular lymphoma, in a warm-blooded animal such as man. That is, the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, is also provided in the manufacture of a medicament for use in the treatment of osteolysis associated with tumors, osteoporosis including bone loss induced by ovariectomy, failure of the orthopedic implant, autoimmune disorders including systemic lupus erythematosus, arthritis including rheumatoid arthritis, osteoarthritis, renal inflammation and glomerulonephritis; inflammatory bowel disease; transplant rejection including renal and bone marrow allografts and xenograft of the skin, atherosclerosis, obesity, Alzheimer's disease and Langerhans cell histiocytosis, in a warm-blooded animal such as man.

That is, a method for producing an inhibitory effect on the CSF-1R kinase is also provided in a warm-blooded animal, such as man, in need of such treatment, the method comprising administering to the animal an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof. That is, a method is also provided to produce an anticancer effect in a warm-blooded animal, such as man, in need of such treatment, the method comprising administering to the animal an effective amount of a compound of formula (I), or pharmaceutically acceptable salt thereof. In other words, a method of treating melanoma, papillary thyroid tumors, cholangiocarcinomas, colon cancer, ovarian cancer, lung cancer, leukemia, lymphoid malignancies, carcinomas and sarcomas of the liver, kidney, bladder, prostate, breast and pancreas is also provided. and primary and recurrent solid tumors of the skin, colon, thyroid, lungs and ovaries, in a warm-blooded animal, such as man, in need of such treatment comprising administering to the animal an effective amount of a compound of formula (I). ) or a pharmaceutically acceptable salt thereof. That is, a method is also provided for treating breast, ovarian, bladder, cervical, endometrial, prostate, lung, kidney and pancreatic tumors; hematological malignancies including medalodisplastic syndrome, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma and chronic lymphocytic leukemia; and glioma, squamous cell carcinoma of the esophagus, malignant melanoma of the uvea and follicular mnfoma, in a warm-blooded animal, such as man, in need of such treatment, the method comprises administering to the animal an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof. That is, a method is also provided for treating osteolysis associated with tumors, osteoporosis including ovarian-induced bone loss, orthopedic implant failure, autoimmune disorders including systemic lupus erythematosus, arthritis including rheumatoid arthritis, osteoarthritis, renal inflammation and glomerulonephritis; inflammatory bowel disease; transplant rejection including renal allografts and bone marrow and xenograft of the skin, atherosclerosis, obesity, Alzheimer's disease and Langerhans cell histocytosis, in a warm-blooded animal, such as man, in need of such treatment, the method comprises administering to the animal an effective amount of a compound of formula (I), or a pharmaceutical salt thereof. That is, a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable diluent or carrier for use in the production of an inhibitory effect on the CSF-kinase is also provided. 1R in a warm-blooded animal such as man. That is, a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable diluent or carrier for use in the production of an anticancer effect in a warm-blooded animal is also provided. just like man. That is, a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable diluent or carrier for use in the treatment of melanoma, papillary thyroid tumors, cholangiocarcinomas, is also provided. colon cancer, ovarian cancer, lung cancer, leukemias, lymphoid malignancies, carcinomas and sarcomas of the liver, kidney, bladder, prostate, breast and pancreas, and primary and recurrent solid tumors of the skin, colon, thyroid, lungs and ovaries in a warm-blooded animal such as man. That is, a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable diluent or carrier, for use in the treatment of breast, ovarian, bladder tumors is also provided. , cervical, endometrial, prostate, lung, kidney and pancreatic; hematologic malignancies including myelodysplastic syndrome, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma and chronic lymphocytic leukemia; and glioma, squamous cell carcinoma of the esophagus, malignant melanoma of the uvea and follicular lymphoma, in a warm-blooded animal such as man. That is, a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable diluent or carrier, for use in the treatment of tumor-associated osteolysis, including osteoporosis, is also provided. bone loss induced by ovariectomy, failure of orthopedic implant, autoimmune disorders including lupus erythematosus sistémico, arthritis including rheumatoid arthritis, osteoarthritis, renal inflammation and glomerulonephritis; inflammatory bowel disease; transplant rejection including renal allografts and bone marrow and xenograft of the skin, atherosclerosis, obesity, Alzheimer's disease and Langerhans cell histiocytosis, in a warm-blooded animal such as man. That is, it is also provided as a compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in the production of an inhibitory effect on the CSF-1R kinase in a warm-blooded animal such as man. That is, it is also provided as a compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in the production of an anticancer effect in a warm-blooded animal such as man. That is, it is also provided as a compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in the treatment of breast, ovarian, bladder, cervical, endometrial, prostate, lung, kidney and pancreatic tumors; hematologic malignancies including myelodysplastic syndrome, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma and chronic lymphocytic leukemia; and glioma, squamous cell carcinoma of the esophagus, malignant melanoma of the uvea and follicular lymphoma, in a warm-blooded animal such as man. That is, it is also provided as a compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in the treatment of tumor-associated osteolysis, osteoporosis including bone loss induced by ovariectomy, failure of orthopedic implant, autoimmune disorders. including sistémic lupus erythematosus, arthritis including rheumatoid arthritis, osteoarthritis, renal inflammation and glomerulonephritis; inflammatory bowel disease; transplant rejection including renal and bone marrow allografts and skin xenograft, atherosclerosis, obesity, Alzheimer's disease and Langerhans cell histiocytosis, in a warm-blooded animal such as man. That is, a process for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof is also provided, comprising: Process a-1) Reacting an amine of formula (A) with an acid of formula B or an activated acid derivative thereof: Process a-2) Reacting an amine of formula (A) with R-N = C = O, wherein R is alkyl of 1 to 6 carbon atoms, aryl, aralkyl, heteroaralkyl, or heteroaryl; Process a-3) Reacting an amine of formula (A) with a chloroformate or an activating agent (for example, carbonyldimidazole, phosgene, or other reagent known to the skilled person), followed by ROH or RR'NH, wherein R is alkyl of 1 to 6 carbon atoms, aryl, heteroaryl, aralkyl, or heteroaralkyl and R 'is H or alkyl of 1 to 6 carbon atoms; Process b) Reacting an acid of formula C or an activated acid derivative thereof: with an amine of formula D: and subsequently if necessary: i) converting a compound of formula (I) to another compound of formula (I); ii) eliminate any of the protection groups; iii) forming a pharmaceutically acceptable salt.

Detailed Description of the Invention Definitions In this specification the term "alkyl" includes the straight and branched chain alkyl groups. References to individual alkyl groups such as "propyl" are specific for the straight chain version only and references to individual branched chain alkyl groups such as 'isopropyl' are specific for the branched chain version only. For example, "C 1-6 alkyl" includes alkyl of 1 to 4 carbon atoms, alkyl of 1 to 3 carbon atoms, propyl, isopropyl and t-butyl. A similar convention applies to other radicals, for example "phenylalkyl of 1 to 6 carbon atoms" includes phenylalkyl of 1 to 4 carbon atoms, benzyl, 1-phenylethyl and 2-phenylethyl. The term "halo" refers to fluoro, chloro, bromo and iodo. Where the optional substituents are chosen from "one or more" groups, it is to be understood that this definition includes all substituents that are chosen from one of the specified groups or the substituents are chosen from two or more of the specified groups. "Heterocyclyl" means a saturated monocyclic, fused, bridged, or partially saturated monocyclic ring system (s) or bicyclic spiro heterocyclic. The monocyclic heterocyclic rings contain from about 3 to 12 ring atoms, with 1 to 5 heteroatoms selected from N, O and S, and preferably from 3 to 7 member atoms, in the ring. The bicyclic heterocycles contain from 7 to 17 member atoms, preferably 7 to 12 member atoms, in the ring. The bicyclic heterocycles contain from about 7 to about 17 ring atoms, preferably from 7 to 12 ring atoms. The bicyclic heterocycle (s) rings can be fused, spiro or bridged ring systems. Examples of heterocyclic groups include cyclic ethers (oxiranes) such as ethylene oxide, tetrahydrofuran, dioxane, and substituted cyclic ethers, wherein the substituents are as specified.

Normal substituted cyclic ethers include propylene oxide, phenyloxirane (styrene oxide), cis-2-buten-oxide (2,3-dimethyloxirane), 3-chlorotetrahydrofuran, 2,6-dimethyl-1,4-dioxane, and the like. The nitrogen-containing heterocycles are groups such as pyrrolidine, piperidine, piperazine, tetrahydrotriazine, tetrahydropyrazole, and substituted groups such as 3-aminopyrrolidine, 4-methylpiperazin-1-lo, and the like. The normal sulfur containing heterocycles includes tetrahydrothiophene, dihydro-oxathiol-4-yl, tetrahydro-oxazolyl, tetrahydro-oxadiazolyl, tetrahydrodioxazolyl, tetrahydro-oxathiazole, hexahydrotriazinyl, tetrahydro-oxazinyl, morpholinyl, thiomorpholinyl, tetrahydropyrimidinyl, dioxolinyl, octahydrobenzofuranyl, octahydrobenzimidazolyl and octahydrobenzothiazolyl. For heterocycles containing sulfur, oxidized sulfur heterocycles containing SO or SO2 groups are also included.

Examples include the tetrahydrothiophene sulfoxide and sulfone forms. "Carbociclílo" is a saturated or partially saturated hydrocarbon ring, which contains from 3 to 6 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. Wherever possible, the cycloalkyl group may contain double bonds, for example, 3-cyclohexen-1-yl. The term "aryl" means a cyclic or polycyclic aromatic ring having from 5 to 12 carbon atoms. The term aryl includes the monovalent species and bivalent species.

Examples of aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-methoxyphenyl, 3-methoxyphenyl. , 4-methoxyphenyl, 2-chloro-3-methylphenyl, 2-chloro-4-methylphenyl, 2-chloro-5-methylphenyl, 3-chloro-2-methylphenyl, 3-chloro-4-methylphenyl, 4-chloro-2 methylphenyl, 4-chloro-3-methylphenium, 5-chloro-2-methylphenyl, 2,3-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,3-dimethylphenyl, 3,4-dimethylphenyl, -trifluoromethyl and the like. "Alkylene" means a group that stands between and serves to connect two other chemical groups. Thus, "(alkyl having 1 to 6 carbon atoms)" means a linear saturated divalent hydrocarbon radical of one to six carbon atoms or a branched saturated divalent hydrocarbon radical of three to six carbon atoms, for example, methylene, ethylene, propylene, 2-methylpropylene, pentylene, and the like.

Aralkyl means a covalent aryl group bonded to an alkylene group (of 1 to 6 carbon atoms), as defined herein. Examples of aralkyl groups include benzyl, phenylethyl, 3- (3-chlorophenyl) -2-methylpentyl, and the like. The term "hetero-tile" means a mono-, bi-, or polycyclic aromatic ring that incorporates one or more heteroatoms (i.e., 1-4) selected from N, O, and S. The term heteroaxis includes the monovalent species and species divalent. Examples of monocyclic heteroaryl include, but are not limited to thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, isoxazolyl, triazolyl, tetrazolyl, piperidyl, pyrazinyl, pyrimidinyl, piperidinyl, pyrrolidinyl, piperazinyl, azetidinyl, aziridinyl, morpholinyl, Tietanyl, substituted or unsubstituted oxetane. Monocyclic diheterocycles include, but are not limited to, 5-imidazolyl, pyrazolyl, isothiazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazinyl, pyrimidinyl, piperazinyl, morpholinyl. Examples of bicyclic and polycyclic heterocycle groups include, but are not limited to, indolizinyl, isoindolyl, indolyl, indazolyl, purinyl, quinolizinyl, quinolinyl, isoquinolinyl, phthalazinyl, naphthyridinyl, quinazolinyl, cinolinyl, pteridinyl, carbazolyl, carbazolyl, carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenatrolinyl, phenazinyl, phenothiazinyl, phenoxazinyl, benzisquinolinyl, thieno [2,3-b] furanyl, pyrazino [2,3-cjcarbazolyl, furo [3,2-b] -pyranyl, pyrido [2,3-d] ] -o-oxazinyl, pyridonyl [4, 3-d] -oxazolyl, midazo [4,5-d] thiazole, pyrazino [2,3-dyrpidazinyl, midazo [2,1-b] t] azolium , furo [3,4-c] cinolinyl, 4H-pyrido [2,3-c] carbazoliol, imidazo [1,2-b] [1,2,4] triazinyl, 7-benzo [b] thienyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzoxapinyl, benzoxazinyl, 1H-pyrrolo [1,2-b] [2] benzazapinyl. Normal heterolated fused groups include, but are not limited to, quinolinyl, isoquinolinyl, indolyl, benzo [b] thienyl, benzoxazolyl, benzimidazolyl, benzothiazolyl. "Heteroaralkyl" means a heteroaryl group covalently bonded to an alkylene group (of 1 to 6 carbon atoms), which is defined herein. Examples of heteroaralkyl groups include pyridin-3-methylmethyl, 3- (benzofuran-2-yl) propyl, and the like. An example of "C 1 -C 6 alkanoyloxy" is acetoxy. Examples of "alkoxycarbonyl of 1 to 6 carbon atoms" include methoxycarbonyl, ethoxycarbonyl, n- and t-butoxycarbonyl. Examples of "C 1 -C 6 -alkoxy" include methoxy, ethoxy and propoxy. Examples of "C 1 -C 6 -alkanoylamino" include formamido, acetamido and propionylamino. Examples of "alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2" include methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl and the isulfonyl. Examples of "C 1 -C 6 -alkanoyl" include propionyl and acetyl.

Examples of "N- (alkyl of 1 to 6 carbon atoms) amino" include methylamino and ethylamino. Examples of "N, N- (alkyl of 1 to 6 carbon atoms) 2-amino" include di-N-methylamino, di- (N-ethyl) amino and N-ethyl-N-methylamino. Examples of "alkenyl of 2 to 6 carbon atoms" are vinyl, allyl and 1-propenyl. Examples of "alkenyl of" alkenyl of 2 to 6 carbon atoms "are ethynyl, 1-propynyl and 2-propynyl Examples of" N- (alkyl of 1 to 6 carbon atoms) sulfamoyl "are N- (methyl) sulfamoyl and N- (ethyl) sulfamoyl Examples of "N- (C 1-6 -alkyl) 2-sulfamoyl" are N, N- (dimethyl) sulfamoyl and N- (methyl) -N- (ethyl) sulfamoyl. "N- (alkyl of 1 to 6 carbon atoms) carbamoyl" are N- (alkyl of 1 to 4 carbon atoms) carbamoyl, methylaminocarbamoyl and ethylaminocarbamoyl.

Examples of "N, N- (alkyl of 1 to 6 carbon atoms) 2carbamoyl" are N, N- (alkyl of 1 to 4 carbon atoms) 2carbamoyl, dimethylaminocarbamoyl and methylethylaminocarbamoyl. Examples of "alkylsulfonyl of 1 to 6 carbon atoms" are mesyl, ethylsulphonyl and isopropylsulphonyl. Examples of "alkylsulfonylamino of 1 to 6 carbon atoms" are mesylamino, ethylsulphonylamino and isopropylsulphonylamino. Examples of "alkoxycarbonylamino of 1 to 6 carbon atoms" are methoxycarbonylamino and t-butoxycarbonylamino. Examples of "N- (alkyl of 1 to 6 carbon atoms) -N- (alkoxy of 1 to 6 carbon atoms) sulfamoyl" are N- (methyl) -N- (methoxy) sulfamoyl and N- (ethyl) - N- (propoxy) sulfamoyl. Examples of "N, N- (alkyl of 1 to 6 carbon atoms) 2ureido" are N, N'-dimethylureido and N-methyl-N-propylureido. Examples of "N ', N' - (alkyl of 1 to 6 carbon atoms) 2ureide" are N ', N'-diethylureido and N'-methyl-N-propylureido. Examples of "N- (C 1-6 -alkyl) -N, N'- (C 1-6 -alkyl) 2-ureido" are N- (methyl) -N'-ethyl-N'-isopropylureido and N-ethyl-N'.N'-diethylureido. Examples of "N- (alkyl of 1 to 6 carbon atoms) -N- (alkoxy of 1 to 6 carbon atoms) amino" are N- (methyl) -N- (propoxy) amino and N-methyl-N- methoxyamine. A suitable pharmaceutically acceptable salt of a compound of the invention is, for example, an acid addition salt of a compound of the invention which is sufficiently basic, for example, an acid addition salt with, for example, an acid inorganic or organic, for example hydrochloric, hydrobromic, sulfuric, phosphoric, trifluoroacetic, citric or maleic acid. In addition, a suitable pharmaceutically acceptable salt of a compound of the invention which is sufficiently acidic is an alkali metal salt, for example a sodium or potassium salt, an alkaline earth metal salt, for example a calcium or magnesium salt, a salt of ammonium or a salt with an organic base which produces a physiologically acceptable cation, for example a salt with methylamine, dimethylamine, trimethylamine, piperidine, morpholine or tris- (2-hydroxyethyl) amine. Some compounds of formula (I) may have chemical centers and / or geometric isomeric centers (E- and Z- isomers), and it is to be understood that the invention comprises all optical, diastereomeric and geometric isomers possessing CSF kinase inhibitory activity. -1R. The invention further relates to any and all tautomeric forms of the compounds of formula (I) which possess kinase inhibitory activity of CSF-1R. It should also be understood that certain compounds of formula (I) may exist in solvated forms as well as unsolvated such as, for example, hydrated forms. It should be understood that the invention comprises all solvated forms that possess CSF-1R kinase inhibitory activity. Preparation of Compounds of the Invention Another aspect of the present invention provides a process for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof, comprising: Process a-1) Reacting an amine of formula (A) with an acid of formula B or an activated acid derivative thereof: Process a-2) Reacting an amine of formula (A) with R-N = C = O, wherein R is alkyl of 1 to 6 carbon atoms, aryl, aralkyl, heteroaralkyl, or heteroaryl; Process a-3) Reacting an amine of formula (A) with a chloroformate or an activating agent (for example, carbonyldiimidazole, phosgene, or other reagent known to the skilled person), followed by ROH or RR'NH, wherein R is alkyl of 1 to 6 carbon atoms, aryl, heteroaryl, aralkyl, or heteroaralkyl and R 'is H or alkyl of 1 to 6 carbon atoms; Process b) Reacting an acid of formula C or an activated acid derivative thereof: with an amine of formula D: and subsequently if necessary: i) converting a compound of formula (I) to another compound of formula (I); ii) eliminate any of the protection groups; iii) forming a pharmaceutically acceptable salt. The specific reaction conditions for the above reactions are as follows. Process a) and Process b) The amines and acids can be combined together in the presence of a suitable combination reagent. The standard peptide combination reagents known in the art can be used as a suitable combination reagent, or for example carbonyldimidazole and dicyclohexylcarbodiimide, optionally in the presence of a catalyst such as dimethylaminopyridine or 4-pyrrolidinepridine, optionally in the presence of a triethylamine, pyridine, or 2,6-di- a / q / u / 7-pyrridines such as 2,6-lutidine or 2,6-di-f erc-butylpyridine. Suitable solvents include dimethylacetamide, dichloromethane, benzene, tetrahydrofuran and dimethylformamide. The combination reaction can be suitably carried out at a temperature in the range of -40 to 40 ° C. Suitable activated acid derivatives include acid halides, for example acid chlorides, and active esters, for example pentafluorophenyl esters. The reaction of these types of compounds with amines is well known in the art, for example it can be reacted in the presence of a base, such as that described above, and in a suitable solvent, such as that described above. The reaction can be suitably carried out at a temperature in the range of -40 to 40 ° C. The amines of formula A can be prepared according to Reaction Scheme 1. Reaction Scheme 1 H, PriC An alternative for the process of Reaction Scheme 1 starting from the corresponding amino compound is represented in Reaction Scheme 2. Reaction Scheme 2 Protect amine A-1 The acids of formula C can be prepared according to Reaction Scheme 3. Reaction Scheme 3 Where Pg is an acid protection group, such as for example he describes hereinafter. It will be appreciated that certain ring substitutes in the compounds of the present invention may be introduced by standard aromatic substitution reactions or generated by modifications of the conventional functional group before or immediately after the processes mentioned above, and as such are included in the aspect of process of the invention.

Such reactions and modifications include, for example, the introduction of a substituent by means of an aromatic substitution reaction, reduction of substituents, alkylation of substituents and oxidation of substituents. The conditions of reagents and reaction for such procedures are well known in the chemical art. Particular examples of aromatic substitution reactions include the introduction of a nitro group using concentrated nitric acid, the introduction of an acyl group uses, for example, an acyl halide and Lewis acid (such as aluminum trichloride) under Friedel Crafts conditions.; the introduction of an alkyl group uses an alkyl halide and Lewis acid (such as aluminum trichloride) under Friedel Crafts conditions; and the introduction of a halogen group. Particular examples of modifications include the reduction of a nitro group to an amino group for example, catalytic hydrogenation with a nickel catalyst or treatment with iron in the presence of hydrochloric acid with heating; oxidation of alkylthio to alkylsulfinyl or alkylsulfonyl. It will also be appreciated that in some of the reactions mentioned herein it may be necessary / desirable to protect any sensitive group in the compounds. Cases where protection is necessary or desirable and suitable methods for protection are known to those skilled in the art. Conventional protection groups can be used in accordance with standard practice (for illustration see T. W. Green, Protective Groups in Organic Synthesis, John Wiley and Sons, 1991). Thus, if the reagents include groups such as amino, carboxy or hydroxy, they may be desirable to protect the group in some of the reactions mentioned herein. A suitable protecting group for an amino or alkylamino group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an alkoxycarbonyl group, for example a methoxycarbonyl group, ethoxycarbonyl or t-butoxycarbonyl, an arylmethoxycarbonyl group, example benzyloxycarbonyl, or an aroyl group, for example benzoyl. The conditions of deprotection for the above protection groups necessarily vary with the choice of the protection group. Thus, for example, an acyl group such as an alkanoyl or alkoxycarbonyl group or an aroyl group can be removed, for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide. Alternatively an acyl group such as a t-butoxycarbonyl group can be removed, for example, by treatment with a suitable acid such as hydrochloric, sulfuric or phosphoric acid or trifluoroacetic acid and an arylmethoxycarbonyl group such as a benzyloxycarbonyl group can be removed, for example, by hydrogenation on a catalyst such as palladium-on-carbon, or by treatment with a Lewis acid for example boron tris (trifluoroacetate). An alternative protecting group suitable for a primary amino group is, for example, a phthaloyl group which can be removed by treatment with an alkylamine, for example dimethylamine propylamine, or with hydrazine. A suitable protecting group for a hydroxy group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an aroyl group, for example benzoyl, or an arylmethyl group, for example benzyl. The conditions of deprotection for the above protection groups will necessarily vary with the choice of the protection group. Thus, for example, an acyl group such as an alkanoyl or an aroyl group can be removed, for example, by hydrolysis with a suitable base such as alkali metal hydroxide, for example lithium or sodium hydroxide. Alternatively an arylmethyl group such as a benzyl group can be removed, for example, by hydrogenation on a catalyst such as palladium-on-carbon. A suitable protecting group for a carboxy group is, for example, an esterification group, for example a methyl or ethyl group which can be removed, for example, by hydrolysis with a base such as sodium hydroxide, or for example a t-group. -butyl which can be removed, for example, by treatment with an acid, for example an organic acid such as trifluoroacetic acid, or for example a benzyl group which can be removed, for example, by hydrogenation on a catalyst such as palladium-on-carbon . The protecting groups can be removed at any suitable stage in the synthesis using conventional techniques well known in the chemical art. As indicated hereinbefore, the compounds defined in the present invention possess anti-cancer activity which is believed to enhance the kinase inhibitory activity of the CSF-1R of the compounds. These properties can be determined, for example, using the procedure indicated below. Biological Activity In vitro AlphaScreen Assay of CSF-1R The activity of purified CSF-1R was determined in vitro using a Homogeneous Amplified Proximity Luminescence Assay (ALPHA) (Perkin Elmer), which measures the substrate phosphorylation of the CSF-1R, the biotinylated poly-glutamine-tyrosine peptide (pE Y-HTRF CisBio 61GT0BLD), as described below. The His-tagged kinase domain of CSF-1R (ie, amino acids 568-912, GeneBank ID NM-005211; (see page 25 lines 13-19 of WO 2006/067445 for sequence listing)) was purified from Baculovirus infected SF + Express insect cells (1.4 x 10 6 cells / ml), by French pressing and chromatographed through columns Qíagen Ni-NTA, Superflow Mono Q HR 10/10, and Superdex 200 SEC subsequent. The normal production was 322 ug / l of the cell pellet at > 95% purity. The phosphorylation of the CSF-1R substrate in the presence and absence of the compound of interest was determined. Briefly, 0.2 pM of the purified CSF-1R, 5 nM of pEY substrate, and the compound were pre-incubated in 1x of buffer for 30 minutes at 25 ° C. Reactions were initiated with the addition of 90 μM of adenosine triphosphate (ATP) in 1x buffer and incubated at 25 ° C for 40 minutes and the reactions stopped by the addition of 5 μl of the mixture. detection consisting of 136 mM NaCl, 102 mM ethylenediamine tetraacetic acid, 1.65 mg / ml BSA, 40 ug / ml Streptavidin donor granules (Perkin Elmer 6760620M), 40 ug / ml pEY100 acceptor granules (Perkin Elmer 6760620M). Plates were incubated at 25 ° C for 18 hours in the dark. The phospho-plated substrate was detected by an EnVision plate reader (Perkin Elmer) 680 nm excitation, 520-620 nm emission. The data was plotted and the calculated Cl50 used Excel Fit (Microsoft). When tested in the above in vitro assay, the compounds of the present invention exhibited activity less than 30 μM. For example, the following results were obtained: Example No. Cl50 (nM) 15 7 nM 20 10 nVI 21 ~? 3 ~ ñM ~ Pharmaceutical Formulations According to a further aspect of the invention there is provided a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein, in association with a pharmaceutically diluent or carrier. acceptable. The composition may be in a form suitable for oral administration, for example as a tablet or capsule, for parenteral injection (including intravenous, subcutaneous, intramuscular, intravascular or infusion) as a sterile solution, suspension or emulsion, for topical administration as an ointment or cream or for rectal administration as a suppository. In general, the above compositions can be prepared in a conventional manner using conventional excipients. The compound of formula (I) will normally be administered to a warm-blooded animal in a unit dose within the range 1-1000 mg / kg, and this normally provides a therapeutically effective dose. Preferably a daily dose in the range of 10-100 mg / kg is used. However, the daily dose will necessarily be varied depending on the treated host, particular route of administration, and severity of the disease to be treated. Therefore, the optimal dosage can be determined by the physician treating any particular patient. USES According to a further aspect of the present invention there is provided a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein above for use in a method of treating the human or animal body by therapy. We have found that the compounds defined in the present invention, or a pharmaceutically acceptable salt thereof, are effective anticancer agents whose property is believed to enhance their CSF-1R kinase inhibitory properties. therefore, the compounds of the present invention are expected to be useful in the treatment of diseases or medical conditions mediated only or in part by the CSF-1R kinase, ie the compounds can be used to produce an inhibitory effect on the CSF kinase. -1R in a warm-blooded animal in need of such treatment. Thus, the compounds of the present invention provide a method for treating cancer characterized by the inhibition of the CSF-1R kinase, ie the compounds can be used to produce an anti-cancer effect mediated alone or in part by the inhibition of the CSF kinase. -1R. Such a compound of the invention is expected to possess a broad range of anticancer properties such as the abnormal expression of CSF1R and / or CSF1 has been observed in multiple human cancers and derived cell lines, including but not limited to, breast, ovarian, endometriotic tumors. , prostate, lung, kidney and pancreatic as well as hematological malignancies including, but not limited to, myelodysplastic syndrome, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma and chronic lymphocytic leukemia. Activation mutations have also been described in haematopoietic and lymphoid tissue and lung cancer. In addition, tumor-associated macrophages have been associated with poor prognosis in multiple tumor types including, but not limited to, breast, endometrial, kidney, lung, bladder and cervical cancers, gloma, squamous cell carcinoma of the esophagus, malignant melanoma of the uvea and follicular lymphoma. It is expected that a compound of the invention possesses anti-cancer activity against these cancers with effect with direct on the tumor and / or indirectly with effect on tumor-associated macrophages. Alternately particular cancers include melanoma, papillary thyroid tumors, cholangiocarcinoma, colon cancer, ovarian cancer, lung cancer, leukemia, lymphoid malignancies, carcinomas and sarcomas in the liver, kidney, bladder, prostate, breast and pancreas, and primary and recurrent solid tumors of the skin, colon, thyroid, lungs and ovaries. In a further aspect of the invention, the compounds of formula (I) may also be of value in the treatment of certain additional indications. These indications include, but are not limited to, tumor-associated osteolysis, osteoporosis including ovarian-induced bone loss, orthopedic implant failure, autoimmune disorders including systemic lupus erythematosus, arthritis including rheumatoid arthritis, osteoarthritis, renal inflammation, and glomerulonephritis.; inflammatory bowel disease; transplant rejection including kidney and bone marrow allografts and skin xenograft, atherosclerosis, obesity, Alzheimer's disease and Langerhans cell histiocytosis. A further aspect of the present invention therefore includes the treatment of one of more of these diseases, particularly arthritis including rheumatoid arthritis and osteoarthritis. Thus according to this aspect of the invention there is provided a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein above for use as a medicament. According to a further aspect of the invention there is provided the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein above in the manufacture of a medicament for use in the production of a inhibitory effect on the kinase of CSF-1R in a warm-blooded animal such as man. According to this aspect of the invention there is provided the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein above, in the manufacture of a medicament for use in the production of a anticancer effect in a warm-blooded animal such as man According to another feature of the invention, there is provided the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein above in the manufacture of a medicament for use in the treatment of melanoma, papillary thyroid tumors, cholangiocarcinomas, colon cancer, ovarian cancer, lung cancer, leukemias, hnfoid malignancies, carcinomas and sarcomas of the liver, bladder, prostate, breast and pancreas, and primary and recurrent solid tumors of the skin, colon, thyroid, lungs and ovaries According to another characteristic of the invention, the use is provided of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein above in the manufacture of a medicament for use in the treatment of breast, ovarian, bladder, cervical, endometrial, prostate, tumors. lung, organ and pancreatic, hematological malignancies including myelodysplastic syndrome, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma and chronic lymphocytic leukemia, and ghoma, squamous cell carcinoma of the esophagus, malignant melanoma of the uvea and follicular disease, in a warm-blooded animal such as man. According to another feature of the invention, there is provided the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein previously, in the manufacture of a medicament for use in the treatment of osteolysis associated with tumor, osteoporosis including loss ovariectomy-induced bone loss, failure of orthopedic implant, autoimmune disorders including lupus erythematosus sistémico, arthritis including rheumatoid arthritis, osteoarthritis, renal inflammation and glomerulonephritis; inflammatory bowel disease; transplant rejection including renal and bone marrow allografts and skin xenograft, atherosclerosis, obesity, Alzheimer's disease and Langerhans cell histiocytosis, in a warm-blooded animal such as man. According to another feature of this aspect of the invention, a method is provided for producing an inhibitory effect on the CSF-1R kinase in a warm-blooded animal, such as man, in need of such treatment, the method comprising administering to the animal an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein above. According to another feature of this aspect of the invention, a method is provided for producing an anti-cancer effect in a warm-blooded animal, such as man, in need of such treatment, the method comprising administering to the animal an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein above. According to a further feature of this aspect of the invention, a method of treating melanoma, papillary thyroid tumors, cholangiocarcinomas, colon cancer, ovarian cancer, lung cancer, leukemias, lymphoid malignancies, carcinomas and liver sarcomas is provided, kidney, bladder, prostate, breast and pancreas, and primary and recurrent solid tumors of the skin, colon, thyroid, lungs and ovaries, in a warm-blooded animal, such as man, in "need of such treatment comprising administering to the animal is an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof as defined hereinbefore .. According to a further feature of the invention, there is provided a method for treating breast, ovarian tumors, bladder, cervical, endometrial, prostate, lung, kidney and pancreatic; haematological malignancies including myelodysplastic syndrome, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma and chronic lymphocytic leukemia; and glioma, squamous cell carcinoma of the esophagus, malignant melanoma of the uvea and follicular lymphoma, in a warm-blooded animal, such as man, in need of such treatment, the method comprises administering to the animal an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof as defined hereinbefore. According to a further feature of the invention, a method is provided for treating osteolysis associated with tumor, osteoporosis including ovarian-induced bone loss, orthopedic implant failure, autoimmune disorders including systemic lupus erythematosus, arthritis including rheumatoid arthritis, osteoarthritis, inflammation renal and glomerulonephritis; inflammatory bowel disease; transplant rejection including kidney and bone marrow allografts and skin xenograft, atherosclerosis, obesity, Alzheimer's disease and Langerhans cell histiocytosis, in a warm-blooded animal, such as man, in need of such treatment, the method comprises administering to the animal an effective amount of a compound of formula (I), or a pharmaceutical salt thereof as defined hereinbefore. In a further aspect of the invention there is provided a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined hereinbefore in association with a pharmaceutically acceptable diluent or carrier for use in the production of an inhibitory effect on the CSF-1R kinase in a warm-blooded animal such as man. In a further aspect of the invention there is provided a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined hereinbefore in association with a pharmaceutically acceptable diluent or carrier for use in the production of an anti-cancer effect in a warm-blooded animal such as man. In a further aspect of the invention there is provided a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined hereinbefore in association with a pharmaceutically acceptable diluent or carrier for use in the treatment of melanoma, papillary thyroid tumors, cholangiocarcinoma, colon cancer, ovarian cancer, lung cancer, leukemia, lymphoid malignancies, carcinomas and sarcomas of the liver, kidney, bladder, prostate, breast and pancreas, and primary and recurrent solid tumors of the skin, colon, thyroid, lungs and ovaries in a warm-blooded animal such as man. In a further aspect of the invention, there is provided a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined hereinbefore, and at least one pharmaceutically acceptable diluent or carrier, for use in the treatment of breast, ovarian, bladder, cervical, endometrial, prostate, lung, kidney and pancreatic tumors; haematological malignancies including myelodysplastic syndrome, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma and chronic lymphocytic leukemia; and glioma, squamous cell carcinoma of the esophagus, malignant melanoma of the uvea and follicular lymphoma, in a warm-blooded animal such as man. In a further aspect of the invention, there is provided a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein above, and at least one pharmaceutically acceptable diluent or carrier , for use in the treatment of tumor-associated osteolysis, osteoporosis including ovarian-induced bone loss, orthopedic implant failure, autoimmune disorders including systemic lupus erythematosus, arthritis including rheumatoid arthritis, osteoarthritis, renal inflammation and glomerulonephritis; inflammatory bowel disease; transplant rejection including kidney and bone marrow allografts and skin xenograft, atherosclerosis, obesity, Alzheimer's disease and Langerhans cell histiocytosis, in a warm-blooded animal such as man. In a further aspect of the invention, there is provided a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein above, for use in the production of an inhibitory effect on the CSF-1R kinase. in a warm-blooded animal such as man. In a further aspect of the invention, there is provided a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined hereinbefore, for use in the production of an anti-cancer effect in a warm-blooded animal such like man. In a further aspect of the invention, there is provided a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein, for use in the treatment of breast, ovarian, bladder, cervical tumors, endometrial, prostate, lung, kidney and pancreatic; hematological malignancies including medelodisplastic syndrome, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma and chronic lymphocytic leukemia; and gloma, squamous cell carcinoma of the esophagus, malignant melanoma of the uvea and follicular lymphoma, in a warm-blooded animal such as man. In a further aspect of the invention, there is provided a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein, for use in the treatment of tumor-associated osteolysis, osteoporosis including bone loss. induced by ovariectomy, failure of orthopedic implant, autoimmune disorders including systemic lupus erythematosus, arthritis including rheumatoid arthritis, osteoarthritis, renal inflammation and glomerulonephritis; inflammatory bowel disease; transplant rejection including renal and bone marrow allografts and skin xenograft, atherosclerosis, obesity, Alzheimer's disease and histiocytosis of Langerhans cells, in a warm-blooded animal such as man. According to a further aspect of the invention there is provided the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein above in the production of an inhibitory effect on the CSF-kinase. 1R in a warm-blooded animal such as man. According to this aspect of the invention there is provided the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein above in the production of an anti-cancer effect in a warm-blooded animal such like man. According to another feature of the invention, there is provided the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein above in the treatment of melanoma, papillary thyroid tumors, cholangiocarcinomas, colon cancer, ovarian cancer, lung cancer, leukemias, lymphoid malignancies, carcinomas and sarcomas of the liver, kidney, bladder, prostate, breast and pancreas, and primary and recurrent solid tumors of the skin, colon, thyroid, lungs and ovaries. The CSF-1R kinase inhibitor treatment defined above may be applied as a single therapy or may involve, in addition to the compound of the invention, conventional surgery or radiotherapy or chemotherapy. Such chemotherapy may include one or more of the following categories of antitumor agents: - (i) antiproliferative / antineoplastic drugs and combinations thereof, as used in medical oncology, such as alkylating agents (eg cis-platinum, carboplatin, cyclophosphamide) , nitrogen mustard, melphalan, chlorambucil, busulfan and nitrosoureas); antimetabolites (for example antifolates such as fluoropyrimidines similar to 5-fluorouracyl and tegafur, raltitrexed, methotrexate, cytosine arabinoside and hydroxyurea; antitumor antibiotics (for example anthracyclines similar to adriamycin, bleomycin, doxorubicin, daunomycin, epirubicin, idarubicin, mithomycin-C, dactinomycin and methramycin), antimitotic agents (for example vinca alkaloids similar to vincristine, vinblastine, vindesine and vinorelbine and taxoids such as taxol and taxotere), and topoisomerase inhibitors (for example epipodophyllotoxins similar to etoposide and teniposide, amsacrine, topotecan and camptothecin); (I) cytostatic agents such as antiestrogens (for example tamoxifen, toremifene, raloxifene, droloxifene and yodoxifen), estrogen receptor lowering regulators (for example fulvestrant), antiandrogens (eg bicalutamide acetate, flutamide, nilutamide and cyproterone) , LHRH antagonists or LHRH agonists (for example goserelin, leuprorelin and buserelin), progestogens (for example megestrol acetate), aromatase inhibitors (for example as anastrozole, letrozole, vorazole and exemestane) and 5a-reductase inhibitors such as Finasteride; (iii) Agents that inhibit cancer cell invasion (eg, metalloproteinase inhibitors such as marimastat and inhibitors of urokinase plasminogen activating receptor function); (iv) inhibitors of growth factor function, for example such inhibitors include growth factor antibodies, growth factor receptor antibodies (e.g. anti-erbb2 antibody trastuzumab [Herceptin ™] and anti-erbb2 antibody cetuximab) erbbl [C225]), farnesyl transferase inhibitors, MEK inhibitors, tyrosine kinase inhibitors and serine / threonine kinase inhibitors, for example inhibitors of the epidermal growth factor family (eg, tyrosine kinase inhibitors of the EGFR family such as j - (3-chloro-4-fluorophenyl) -7-methoxy-6- (3-morpholinpropoxy) quinazolin-4-amine (gefitinib, AZD 1839), N _- (3-ethynyl nil) -6.7 -bis (2-methoxyethoxy) quinazolin-4-amine (erlotinib, OSI-774) and 6-acrylamido-N- (3-chloro-4-fluorophenyl) -7- (3-morpholinpropoxy) quinazolin-4-amine (Cl 1033)), for example inhibitors of the family of the derived growth factor of platelet and for example inhibitors of the hepatocyte growth factor family; (v) antiangiogenic agents such as those that inhibit the effects of vascular endothelial growth factor, (e.g. bevacizumab of anti-vascular endothelial cell growth factor antibody [Avastin ™], compounds such as those described in Patent Applications International WO 97/22596, WO 97/30035, WO 97/32856 and WO 98/13354) and compounds that work by other mechanisms (for example, linomide, inhibitors of the function of integrin avß3 and angiostatin); (vi) harmful vascular agents such as Combretastatin A4 and compounds described in International Patent Applications WO 99/02166, WO00 / 40529, WO 00/41669, WO01 / 92224, WO02 / 04434 and WO02 / 08213; (vii) antisense therapies, for example those that target targets listed above, such as ISIS 2503, an anti-ras antisense; (vii) gene therapy processes, including for example processes to substitute abnormal genes such as abnormal p53 or BRCA1 or abnormal BRCA2, GDEPT (pro-drug gene-directed enzyme therapy) processes such as those using cytosine deaminase, thymidine kinase or a bacterial nitroreductase enzyme and processes for increasing patient tolerance to chemotherapy or radiotherapy such as multi-drug resistance gene therapy; (ix) immunotherapy processes, including for example ex-vivo and in-vivo processes to increase the immunogenicity of tumor cells in patients, such as transfection with cytokines such as interleukin 2, interleukin 4 or stimulation factor of the granulocyte colony - macrophage, processes to decrease the energy of T cells, processes using transfected immune cells such as dendritic cells transfected with cytokine, processes using tumor cell lines transfected with cytokine and using antidiotypic antibodies; (x) cell cycle inhibitors including for example CDK inhibitors (e.g. flavopiridol) and other cell cycle checkpoint inhibitors (e.g., checkpoint kinase); inhibitors of aurora kinase and other kinases involved in the regulation of mitosis and cytokinesis (for example, mytotic kinesins); and histone deacetylase inhibitors; and (xi) endothelin antagonists, including endothelin A antagonists, endothelin B antagonists and endothelin A and B antagonists; for example ZD4054 and ZD1611 (WO 9640681), atrasentan and YM598. Such joint treatment may be carried out by means of simultaneous, sequential or separate dosing of the individual components of the treatment. Such combination products utilize the compounds of this invention within the dosage range described hereinbefore and the other pharmaceutically-active agent within their approved dosage range. In addition to their use in therapeutic medicine, the compounds of formula (I) and their pharmaceutically acceptable salts are also useful as pharmacological tools in the development and standardization of in vitro and in vivo test systems for the evaluation of the effects of inhibitors of the CSF-1R kinase in laboratory animals such as cats, dogs, rabbits, monkeys, rats and mice, as part of the search for new therapeutic agents. In another prior pharmaceutical composition, process, method, use and manufacturing characteristics of the medicament, and alternative and preferred embodiments of the compounds of the invention described herein are also applied. Examples The invention will now be illustrated by the following non-limiting examples in which, unless otherwise indicated: (i) temperatures are given in degrees centigrade (° C); the operations were carried out at room or ambient temperature, that is, at a temperature in the range of 18-25CC; (I) the organic solutions were dried over anhydrous sodium sulfate; the evaporation of the solvent was carried out using a rotary evaporator under reduced pressure (600-4000 Paséales, 4.5-30 mmHg) with a bath temperature of up to 60 ° C; (i) In general, the course of the reactions was followed by TLC and the reaction times are given for illustration only; (iv) the final products have a satisfactory proton nuclear magnetic resonance (NMR) spectrum and / or mass spectral data; (v) the returns are given for illustration only and are not necessarily those that can be obtained by the development of the diligent process; the preparations were repeated if more material is required; (vii) when given, the NMR data in the form of delta values for the important diagnostic protons, given in parts per million (ppm) relative to tetramethylsilane (TMS) as an internal standard, determined at 400 MHz using perdeuterio dimethylsulfoxide (DMSO-d6) as a solvent unless otherwise indicated; (vii) chemical symbols have their usual meanings; SI units and symbols are used; (vi i i) the proportions of solvent are given in terms of volume: volume (v / v); and (ix) mass spectra are produced with an electron energy of 70 electron volts in the chemical ionization (Cl) mode using a direct exposure test; where the indicated ionization was effected by electron impact (EL), fast atom bombardment (FAB) or electroasperción (ESP); values for m / z are given; generally, only the ions that indicate the sourdough were reported; and unless otherwise indicated, the quoted mass ion is (MH) *; (x) where a synthesis is described as being analogous to that described in a previous example, the amounts used are the proportion equivalents in millimolar to those used in the previous example; - (xi) the following abbreviations have been used: HATU 0- (1-azabenzotriazol-1-yl) - N, N, N ', N'-tetramethyluronium hexafluorophosphate; THF tetrahydrofuran; DMF N, N-dimethylformamide; EtOAc ethyl acetate; DIEA N, N-diisopropylethylamine; DCM dichloromethane; DMSO dimethyl sulfoxide; MeCN acetonitrile; MeOH methanol; and DPPA Diphenylphosphorylazide (xii) "ISCO" refers to normal normal phase flash column chromatography using pre-packaged 12 g and 40 g cartridges of silica gel used according to the manufacturer's instruction obtained from ISCO, Inc, 4700 Superior Street Lincoln, NE, USA; and (xiii) "Gilson CLAR" refers to a reverse phase CLAR column of YMC-AQC 18 with dimension 20 mm / 100 and 50 mm / 250 in water / MeCN with 0.1% TFA as mobile phase, (xiv) ) Hydrogenator Parr or hydrotreaters type Parr shaker obtained 0 systems to treat chemical products with hydrogen in the presence of a catalyst at pressures of up to 5 atmospheres (60 psig) and temperatures at 80 ° C. Preparation of Starting Materials Method 1 1, 3-thiazole-5-amine To a solution of 1,3-thiazole-5-carboxylic acid (728 mg, 5.6 mmol) in tert-BuOH (19 ml) was added Et3N (2.4 mi, 17 mmol) and DPPA (2.5 mL, 11.3 mmol) and the resulting dark red solution was heated to reflux for 8 hours. After cooling, EtOAc was added, and the organic layer was washed with saturated NaHCO3 solution, water, brine, and dried (MgSO4). Evaporation of the solvents under reduced pressure afforded tere-butyl 1,3-thiazole-5-ylcarbamate (500 mg), which was used in the next step without further purification, m / z: 201. To a solution of 1, Tere-butyl 3-thiazole-5-ylcarbamate (500 mg) in MeOH (10 mL) at 0 ° C was slowly added a solution of 4N HCl in dioxane (5 mL) and the resulting yellow solution was stirred at room temperature. environment for 2 hours. The title compound was isolated as a pale yellow solid after filtration (150 mg) as its hydrochloride salt, m / z: 101. Method 2 2-methyl-1,3-thiazole-5-amine A Amineacetonitrile bisulfate solution (6.4 g, 41.6 mmol) in anhydrous MeOH (75 ml) at 0 ° C was added Et3N (11.6 ml, 83 mmol). After 30 minutes, ethyl dithioacetate (5 g, 41.6 mmol) was added and the resulting dark orange solution was stirred at room temperature for 2 hours. Half the solvent was removed under reduced pressure. The solution was diluted with an equivalent volume of EtOAc, washed with water, and dried (Na2SO4). The solvents were removed under reduced pressure and the residue was suspended in hot EtOAc, cooled in an ice bath, and filtered to give 2.45 g (52%) of a brown solid. H NMR DMSO-d6: 6.62 (s, 1 H) 5.36 (broad, 2 H) 2.89 (s, 3 H); m / z: 115. Method 3 5-amino-N-methyl-1,3-thiazole-2-carboxamide To a solution of 2-chloro-N-methyllacetamide (1.0 g, 9.3 mmol) in DMF (10 mL) was added Et3N (2.9 ml) and sulfur (595 mg, 18.6 mmol). After 2 hours, methyl iodide (0.6 ml, 10.2 mmol) was added and the dark solution was stirred at room temperature for additional 3 hours. The reaction mixture was partitioned between EtOAc and water, and the organic layer was washed with 1N sodium thiosulfate solution, water, and dried (MgSO4). Evaporation of the solvents gave methyl 3- (methylamino) -3-oxoethane (dithioate) (300 mg), which was used without further purification in the next step. To a solution of aminoacetonitrile bisulfate (400 mg) in EtOAc (10 mL) was added Et3N (5 mL) and methyl 3- (methylamino) -3-oxoethane (dithioate) (300 mg), and the solution was orange The resulting dark was stirred at room temperature for 18 hours. The title compound was isolated via filtration (50 mg). m / z: 158. Methods 4 and 5 The following compounds were prepared by a procedure analogous to that of Method 3, using the appropriate starting material.

Method 6 3- (1-Cyano-1-methylethyl) benzoic acid A solution of 3- (1-centao-1-methyl-ethyl) benzoic acid methyl ester (Method 14, 5.5 g, 27.1 mmol) in 100 ml of THF / MeOH / water (3: 1: 1) was treated with lithium hydroxide (1.95 g) in 20 ml of water. The mixture was stirred at room temperature for 12 hours. The solvent was removed under reduced pressure and the resulting solution was diluted with water, then acidified with 10% HCl to pH ~ 2. The resulting white solid (4.83 g, 94%) was filtered, washed with water and dried. H NMR: 13.00 (s, 1H), 7.95 (s, 1H), 7.80 (d, 1H), 7.65 (d, 1H), 7.45 (m, 1H), 1.60 (s, 6H); m / z: 189. Methods 7 to 13 The following compounds were prepared by a process analogous to that of Method 6, using the appropriate starting material.

Method 14 3- (1-Cyano-1-methylethyl) benzoic acid methyl ester A solution of 3-cyanomethyl-benzoic acid methyl ester (Method 15, 7.2 g, 41.1 mmol) in anhydrous DMSO (80 mL) was treated with NaH ( 60% in mineral oil, 4.9 g, 123.3 mmol). Methyl iodide was added dropwise at 0 ° C. The reaction mixture was stirred at room temperature for 12 hours, quenched with water (200 ml) and extracted with EtOAc. The combined organics were dried and concentrated under reduced pressure. The crude product was purified by column chromatography using an ISCO System (hexane-EtOAc) to give 5.5 g (66%) of a colorless oil. H NMR: 8.05 (s, 1H), 7.90 (d, 1H), 7.75 (d, 1H), 7.55 (m, 1H), 3.80 (s, 3H), 1.62 (s, 6H); m / z: 203.

Method 15 3-Cyanomethyl-benzoic acid methylester A suspension of methyl-3- (bromomethyl) benzoate (13.5 g, 58.9 mmol) and sodium cyanide (4.33 g, 88.4 mmol) in DMF (25 mL) and water (1 mL) ) was stirred at 75 ° C for 5 hours. The reaction mixture was quenched with water (50 ml), extracted with EtOAc (3 x 100 ml) and the combined organics were dried and concentrated under reduced pressure. The residue was purified by column chromatography using an ISCO system (hexane-EtOAc) to give 7.2 g (70%) of a colorless oil. 1 H NMR: 7.90 (s, 1 H), 7.86 (d, 1 H), 7.60 (d, 1 H), 7.50 (m, 1 H), 4.10 (s, 2 H), 3.80 (s, 3 H); m / z: 175 Method 16 5-. { methyl r3- (1-cyano-1-methylethyl) benzoylamino) -2-methylbenzoate A solution of methyl 5-amino-2-methylbenzoate (Method 22), 2.7 g, 16.4 mmol), 3- (1-cyano-1-methylethyl) benzoic acid (Method 6, 3.13 g, 16.6 mmol) and N, N-diisopropylethylamine (8.67 mL, 49.8 mmol) in DMF (33 mL) at 0 ° C was treated with HATU (9.47 g, 24.9 mmol). The reaction was stirred at room temperature for 24 hours, quenched with water (30 mL) and extracted with EtOAc (100 mL). The organic layer was washed with brine (200 ml), dried (MgSO 4) and concentrated under reduced pressure to give 5.58 g of a reddish-brown oil, m / z: 336.

Methods 17 and 18 The following compounds were prepared by a process analogous to that of Method 16, using the appropriate starting material and methyl 5-amino-2-chlorobenzoate of Method 24.

Method 19 2-chloro-5-. { [Methyl 3-fluoro-5- (trifluoromethyl) benzoyl) amino) benzoate To a solution of methyl 5-amino-2-chlorobenzoate (Method 24, 2.25 g, 12.1 mmol) and triethylamine (2.53 ml, 18.2 mmol) in DCM (15 mL) at 0 ° C was added 3-fluoro-5- (trifluoromethyl) benzoyl chloride (3.02 g, 13.3 mmol). After 1.5 hours, the reaction mixture was diluted with DCM (100 mL), washed with 1N HCl (30 mL), water (30 mL), brine (30 mL) and dried (MgSO4). The crude product was recrystallized from EtOAc: Hex (3 cultures) to give 3.55 g (78%) of the white solid. 1 H NMR CDCl 3 8.05 (s, 1 H), 7.86 (m, 3 H), 7.79 (d, 1 H), 7.55 (d, 1H), 7.48 (d, 1H), 3.94 (s, 3 H); m / z: 374. Methods 20 and 21 The following compounds were prepared by a process analogous to that of Method 19, using the appropriate starting material and 3- (trifluoromethyl) benzoyl chloride.

Method 22 Methyl 5-amino-2-methylbenzoate A solution of methyl 2-methyl-5-nitrobenzoate (Method 23, 3.4 g) and 10% palladium on carbon (672 mg) in MeOH (20 ml) was treated with H2 for 48 hours. The reaction mixture was then filtered through diatomaceous earth and washed with MeOH (20 mL) and EtOAc (10 mL). The solvents were removed under reduced pressure to give 2.7 g of a brown oil. 1 H NMR: 7.11 (d, 1H), 6.94 (d, 1H), 6.69 (dd, 1H), 5.13 (s, 2H), 3.78 (s, 3H), 2.33 (s, 3H); m / z: 165. Method 23 Methyl 2-methyl-5-nitrobenzoate A solution of 2-methyl-5-nitrobenzoic acid (3.9 g, 21.5 mmol) in MeOH (20 mL) was treated with HCl gas for 10 min. . The reaction was then refluxed in a sealed tube at 65 ° C for 24 hours. The solvent was evaporated to give a cream colored solid (4.8 g), which was dissolved in EtOAc (200 mL), washed with water (200 mL), brine (200 mL), and dried (MgSO4). The solvents were removed under reduced pressure to give 3.4 g of a white solid. 1 H NMR: 8.48 (d, 1H), 8.27 (dd, 1H), 7.60 (d, 1H), 3.87 (s, 3H), 2.60 (s, 3H); m / z: 196. Method 24 Methyl 5-amino-2-chlorobenzoate Thionyl chloride (1.30 ml, 17.8 mmol) was added to a solution of 5-amino-2-chlorobenzoic acid (3.06 g, 17.8 mmol) in MeOH (20 mi). The reaction mixture was stirred for 16 hours, concentrated and the residue was dissolved in EtOAc (150 mL). The organic layer was washed with saturated NaHCO3 solution (75 ml), water (50 ml), brine (50 ml) and dried (MgSO4). The solvents were removed under reduced pressure to give 2.25 g (68%) of a colorless oil. 1 H NMR CDCl 3 7.18 (d, 1H), 7.11 (d, 1H), 6.71 (dd, 1H), 3.90 (s, 3 H); m / z: 186. Method 25 5-amino-2-methyl-N- (2-methyl-1,3-thiazol-5-yl) benzamide A solution of tert -butyl (4-methyl-3- { [( 2-methyl-1,3-thiazol-5-yl) amino] carbonyl. Phenyl) carbamate (Example 84, 3.4 g, 9.79 mmol) in MeOH was treated with HCl gas for 30 minutes. The reaction mixture was stirred for 20 hours, and concentrated. The crude product was recrystallized from MeOH to give 1.8 g (74%) of a white solid, m / z: 248.

Method 26 The following compound was prepared by a process analogous to that of Method 25, using the appropriate starting material.

Method 27 5-R (tert-butoxycarbonyl) amino-2-methylbenzoic acid A solution of methyl 5 - [(tert-butoxycarbonyl) amino] -2-methylbenzoate (Method 29, 14.8 g, 55.9 mmol) in MeOH: THF: Water (1: 1: 1, 300 ml) was treated with KOH (5 equivalents) and stirred for 20 hours. The organic solvent was removed under reduced pressure, and the remaining aqueous phase was acidified to pH = 4 with dilute HCl. The aqueous phase was extracted with EtOAc and the organic layer was dried (Na2SO4) and concentrated to give 12.1 g (86%) of a white solid. 1 H NMR: 9.28 (s, 1 H), 7.80 (s, 1 H), 7.36 (dd, 1 H), 7.04 (d, 1 H), 2.37 (s, 3 H), 1.45 (s, 9 H). Method 28 The following compound was prepared by a process analogous to that of Method 27, using the appropriate starting material.

Method 29 methyl 5-r (-butoxycarbonyl) aminol-2-methylbenzoate To a solution of methyl 5-amino-2-methylbenzoate (Method 22, 4.3 g, 26.0 mmol) in THF (160 ml) and wa(40 ml). mi) was added di--butyldicarbonate (17.0 g, 78.1 mmol) and K2CO3 (10.8 g, 78.1 mmol). The reaction mixture was stirred for 16 hours, the organic solvent was removed under reduced pressure, and the remaining aqueous phase was extracted with EtOAc. Afconcentration of the organic layer, chromatography afforded 6.2 g (90%) of a white solid. 1 H NMR: 9.46 (s, 1H), 8.05 (d, 1H), 7.47 (dd, 1H), 7.19 (d, 1H), 3.81 (s, 3H), 2.42 (s, 3H), 1.47 (s, 9 H). Method 30 The following compound was prepared by a process analogous to that of Method 29, using the appropriate starting maal.

Method 31 3-Cyclopropyl-5-fluorobenzoic acid To a solution of 3-bromo-5-fluorobenzoic acid (0.500 g, 4.56 mmol) and cyclopropylboronic acid (0.590 g, 6.84 mmol) in toluene (15 mL) and wa(0.75 mmol). mi) was added K3PO (3.86 g, 18.24 mmol) and Pd (PPh3) 4 (1.05 g, 0.912 mmol). The reaction mixture was heated at 100 ° C for 12 hours, cooled to room temperature, and quenched with 10% aqueous NaOH (100 ml). The reaction mixture was washed with EtOAc (100 ml) and the resulting aqueous layer was isolated and brought to a pH of ~2 by careful addition of 3N HCl. The resulting precipitate was fild, washed with wa(100 ml), and dried under vacuum for 24 hours to give 0.31 g (37%) of the whitish solid; m / z: 181. Method 32 3-Cyclopropylbenzoic acid To a solution of zinc diethyl (12.3 ml, 1M in hexanes) in DCM (20 ml) at 0 ° C was added dropwise via syringe with trifluoroacetic acid (1.40 g). , 12.3 mmol), and af20 minutes stirred, diiodomethane (3.30 g, 12.3 mmol). Af20 minutes, methyl 3-vinylbenzoate (1.00 g, 6.16 mmol) was added, and the cooling bath was removed. Af3 hours, the reaction was quenched by the addition of saturated NH 4 Cl solution (50 ml). The aqueous phase was extracted with DCM (3 x 50 mL), and the combined organic extract was dried (MgSO4) and concentrated in vacuo to give the crude reaction product which was purified by column chromatography (hexanes / EtOAc 10: 1) to give 1.01 g (94%) of methyl 3-cyclopropylbenzoate as a colorless oil; m / z: 111. To a solution of methyl-3-cyclopropylbenzoate (0.275 g, 1.56 mmol) in MeOH (10 mL) and H2O (1 mL) was added LiOH-H2O (0.131 g, 3.00 mmol). Af3 hours the pH was adjusted to -3 by the addition of 3N HCl, and the aqueous phase was extracted with EtOAc (3 X 25 mL). The combined organic extract was washed with brine (25 mL), dried (MgSO), and concentrated in vacuo to provide 0.192 g (76%) of the white solid; m / z: 161. Method 33 2-isopropyl-1,3-thiazole-5-amine A solution of 2-methylpropanoic acid (2.5 g, 28.8 mmol) in 1,4-trichlorobenzene (5 mL) was added to a suspension of 2.4 2,4-bis (methylthio) -1,2,4,4-dithiadiphosphine (Davy Reagent) disulfide (5 g, 15.85 mmol) in 1,4-trichlorobenzene (20 ml) at room temperature. The resulting yellow reaction mixture was heated at 130 ° C for 10 min. The crude methyl 2-methylpropane dithioate was collected with 1, 2,4-trichlorobenzene via vacuum distillation, which was used in the next step without any further purification. The aminoacetonitrile (4.43 g, 28.8 mmol) in 40 mL of methanol was treated with TEA (5.8 g, 57.6 mmol). The reaction was then cooled to 0 ° C and methyl 2-methylpropane dithioate (-28 mmol) in 1,2,4-trichlorobenzene was added to the reaction with an addition funnel for 15 minutes. The resulting reaction mixture was allowed to stir at room temperature for 2 days before concentrating in vacuo. The residue was partitioned between waand chloroform, separated, and the aqueous phase was further extracted with CHCl3. The organic layers were combined, dried over anhydrous sodium sulfate, fild, the filtrate was concentrated in vacuo to give the crude product. The residue was purified on 120 g of SiO2 using hexanes: EtOAc (1: 1) as eluent to give 0.620 g (15% over two steps) of the title compound as a brown solid. 1 H NMR (400MHz, DMSO): 6.55 (s, 1H), 5.30 (s, 2H), 3.00 (m, 1H), 1.20 (d, 6H); m / z: 142. Method 34 The following compound was prepared by the method of Method 33, using the appropriate starting maal.

Method 35 Difluoro (2-ydocyclohexyl) ethyl acetate Cyclohexene (1.64 g, 20 mmol) and ethyl iododifluoroacetate (5 g, 20 mmol) were dissolved in a solvent system of water (20 ml) and acetonitrile (20 ml). Dithionite sodium (7.4 g) and sodium bicarbonate (3.7 g) were then added to the solution. The mixture was allowed to stir at room temperature for 12 h. The reaction was then treated with water (-100 mL), poured into a separatory funnel, and extracted with ether (3 x 40 mL). The combined organic layer was washed with saturated aqueous NaCl, dried over anhydrous sodium sulfate, and concentrated in vacuo to provide the crude product which was purified via SiO2 chromatography using hexane-EtOAc (9: 1) as eluent to give 4.9 g (74%) of the title compound as a mixture of diastereoisomers. Method 36 Ethyl cyclohexyl (difluoro) acetate A flask was fitted with a stir bar and a capped condenser with a nitrogen inlet which was charged with Zinc (s) (1.92 g, 29.5 mmol), NiCI2.6H2O (0.354 g) , 1.476 mmol), 2.5 drops of water, and 25 ml of THF. The resulting mixture was stirred at 25 ° C for 15 min, and then ethyl difluoro (2-iodocyclohexyl) acetate (Method 35) (4.9 g, 14.76 mmol) was added and the reaction was stirred for 4 h. The reaction mixture was then poured into a saturated aqueous NH 4 Cl solution and extracted with ether (3 x 30 mL). The combined organic phase was dried with MgSO, filtered, and concentrated in vacuo to give the crude product which was purified via SiO2 chromatography using hexane-EtOAc (9: 1) as eluent to give 1.5 g (49%) of the title as a light yellow oil. Example 1 5- (r 3 - (1-cyano-1-methylethyl) benzoylamino) -2-methyl-N- (2-methyl-1,3-thiazol-5-yl) benzamide A solution of 5- acid. { [3- (1-cyano-1-methyl-ethyl) -benzoyl] -amino} -2-methylbenzoic acid (Method 7.82 mg, 0.25 mmol), 2-methyl-1,3-thiazole-5-amine (Method 2, 28 mg, 0.25 mmol), HATU (101 mg, 0.275 mmol) and N, N- Diisopropyletilamine (0.135 ml) in DMF (0.5 ml) was stirred for 16 hours at room temperature. The reaction mixture was partitioned between water and EtOAc, and the organic layer was washed with brine and dried (MgSO4). Purification by reverse HPLC (5% -95% water-MeCN, 15 minutes) provided 51 mg (48%) of the title compound after evaporation of the solvents. 1 H NMR CDCl 3 11.80 (s, 1 H), 10.39 (s, 1 H), 8.64 (s, 1 H), 7.90-8.02 (m, 3 H), 7.78-7.81 (m, 2 H), 7.60 (t, 1 H), 7.35 (d, 1H), 2. 49 (s, 3H) 2.39 (s, 3H), 1.76 (s, 6H); m / z 419. Examples 2-24 The following compounds were prepared by a process analogous to that described in Example 1 using 1,3-thiazol-5-amine (Method 1), 2-methyl-1,3-thiazole-5 -amine (Method 2), 5-amino-N-methyl-1,3-thiazole-2-carboxamide (Method 3), 2- (morpholin-4-ylcarbonyl) -1, 3-thiazole-5-amine (Method 4), 5-amino-N-methoxy-N-methyl-1,3-thiazole-2-carboxamide (Method 5), 2-isopropyl-1,3-thiazole-5-amine (Method 33), or 2- cyclopropyl-1, 3-thiazol-5-amine (Method 34), and the appropriate starting material. In some cases, alternative purification methods were required (column chromatography or recrystallization of EtOAc: Hex).

Example 25 5-. { [3-Fluoro-5- (tri-fluoro-methyl) -benzoylamino) -2-methyl-N- (2-methyl-1,3-thiazol-5-yl) -benzamide To a solution of 5-amino-2-methyl -N- (2-methy! -1, 3-thiazol-5-yl) benzamide (Method 25, 100 mg, 0.40 mmol) and 3-fluoro-5- (trifluoromethyl) benzoic acid (85 mg, 0.40 mmol) in Anhydrous DMF (5 mL) was added HATU (154 mg, 0.40 mmol) and pyridine (5 equivalents). After it was stirred for 16 hours, the reaction mixture was diluted with EtOAc, washed with water, dried (Na2SO4) and concentrated. Purification by column chromatography (Hex: EtOAc) gave 121 mg (68%) of a white solid. 1 H NMR Acetone-d 6 10.70 (s, 1 H), 9.94 (s, 1 H), 8.19 (s, 1 H), 8.08 (s, 1 H), 8.04 (d, 1 H), 7.80 (dd, 2 H), 7.49 (s) , 1H), 7.32 (d, 1H), 2.60 (s, 3H), 2.43 (s, 3 H); m / z: 438. Examples 26-66 The following compounds were prepared by a process -analog to that described in Example 25 using 5-amino-2-methyl-N- (2-methyl-1,3-thiazol-5-yl) benzamide (Method 25) or 5-amino-2-chloro- N- (2-methyl-1,3-thiazol-5-yl) benzamide (Method 26) and the appropriate MS.

Example 67 2-chloro-N- (2- d? Metí lamí no) met? 11-1.3-t? Azol-5-? L) -5-ir3- (tr? Fluoromet? L) benzo? Llam? No} benzamide To a 10 ml round bottom flask loaded with a magnetic stir bar and 2-chloro-N- (2-formyl-1,3-t-azol-5-yl) -5. { [3 (trifluoromethyl) benzoyl] amino} benzamide (0.123 g, 0.272 mmol) (Example 86) anhydrous THF (3 mL) was added. A 2M solution of dimethylamine in TNF (0.34 mL, 0.68 mmol) was added to the reaction followed by the addition of glacial acetic acid (0.050 mL, 0.83 mmol). With stirring, NaBH (OAc) 3 (0.23 g, 1.09 mmol) was added and the reaction was heated to 50 ° C and allowed to stir at this temperature for 5 h before being diluted with a saturated aqueous solution of NaHCO 3 (~ 5 mL). ). The mixture was then poured into a separatory funnel and extracted with EtOAc (-50 mL) and washed with 2 x 50 mL of saturated aqueous NaHCO3 solution.

The organic phase was separated, dried with MgSO 4, filtered, and concentrated, in vacuo to give the crude product. The crude product was purified via reverse phase HPLC using MeCN / H2O (1: 1) as eluent which gave the title compound as an off white solid; DMSO-D6 12.32 (s, 1H), 10.79 (s, 1H), 8.24- 8.34 (m, 2 H) 8.12 (d, 1H), 7.89-8.03 (m, 2H), 7.81 (t, 1H), 7.72 (s, 1H), 7.56-7.67 (m, 1H), 4.56-4.69 (m, 2H), 2.82 (s, 6 H); m / z: 483. Examples 68-81 The following compounds were prepared by a process analogous to that described in Example 67 using 2-chloro-N- (2-formyl-1,3-thiazol-5-yl) -5- . { [3 (trifluoromethyl) benzoyl] amino} benzamide (Example 86), 2-chloro-5 - [(3,5-dimethylbenzoyl) amino] -N- (2-formyl-1,3-thiazol-5-yl) benzamide (Example 87), or 5-. { [3- (1-cyano-1-methyl-ethyl) -benzoyl] -amino} -N- (2-formyl-1,3-thiazol-5-yl) -2-methylbenzamide (Example 88) and the appropriate MS.

EXAMPLE 82 2-Vo-ro-N- (2-formi 1-1, 3-ti azol-5-in-5-U3- (trifluoromethyl I) benzoi II amino) benzamide To a 25 ml round bottom flask loaded with a magnetic stirring bar and 2-chloro-N- (2-formyl-1,3-ti-azol-5-yl) -5-. { [3 (trifluoromethyl) benzoyl] amino} benzamide (0.28 g, 0.58 mmol) (Example 86) methanol (5 ml) was added. Sodium borohydride (0.66 g, 1.74 mmol) was added and the reaction was allowed to stir at room temperature for 1 h before being diluted with a saturated aqueous solution of NH CI (-20 mL). The mixture was then poured into a separatory funnel and extracted with EtOAc (-50 mL). The organic phase was separated, dried with MgSO 4, filtered, and concentrated, in vacuo to give the crude product. The crude oil was purified on SiO2 (40 g) using EtOAc as eluent which gave the title compound as a white solid; DMSO-D6 11.88 (s, 1H), 10.74 (s, 1H), 8.24-8.32 (m, 2H), 7.93-8.04 (m, 3H), 7.80 (t, 1H), 7.60 (d, 1H), 7.49 (s, 1 H), 4.66 (s, 2 H); m / z: 456. Example 83 2-cl or ro-N-r2- (1-hydroxyethyl) -1,3-ti-azol-5-yl-5- (r3- (trifluoromethyl) benzoipamino) benzamide To a flask of 10 ml round bottom loaded with a magnetic stir bar and 2-chloro-N- (2-formyl-1,3-ti-azol-5-yl) -5-. { [3 (tpfluoromethyl) benzoyl] amino} Benzamide (0.071 g, 0.16 mmol) (Example 86) was added anhydrous THF (2.5 mL) and the reaction was cooled to 0 ° C. A 3M solution of magnesium methyl bromide in Et2O (0.15 ml, 0.468 mmol) was added to the reaction via a syringe and the resulting mixture was allowed to stir at 0 ° C for 0.5 h before being diluted with a saturated aqueous solution of NH4CI ( -20 mi). The mixture was then poured into a separatory funnel and extracted with EtOAc (-50 mL). The organic phase was separated, dried with MgSO 4, filtered, and concentrated, in vacuo to give the crude product. The crude oil was purified on SiO2 (40 g) using EtOAc as eluent which gave the title compound as a white solid; DMSO-D6 11.82 (s, 1H), 10.73 (s, 1H), 8.24-8.34 (m, 2H), 7.93-8.03 (m, 3H), 7.80 (t, 1H), 7.60 (d, 1H), 7.47 (s, 1H), 6.00 (s, 1H), 4.87 (q, 1H), 1.43 (d, 3 H); m / z: 470. EXAMPLE 84 Tere-Butyl (4-methyl-3-. {r (2-methyl-1,3-thiazol-5-yl) amino-1-carbonyl) phenylD-carbamate To a solution of 5 - [(tert. -butoxycarbonyl) amino] -2-methylbenzoic acid (Method 27)2.9 g, 11.5 mmol) and 2-methyl-1,3-thiazol-5-amine (Method 2, 1.3 g, 11.4 mmol) in anhydrous DMF (10 mL) was added HATU (4.4 g, 11.6 mmol) and pyridine. (4.6 ml, 56.9 mmol, 5 equivalents). After it was stirred for 16 hours, the reaction mixture was diluted with EtOAc, washed with water, dried (Na2SO4) and concentrated. Purification by chromatography gave 3.4 g (85%) of a white solid. 1 H NMR 11.54 (s, 1H), 9.46 (s, 1H), 7.62 (s, 1H), 7.39-7.42 (m, 2H), 7.18 (d, 1H), 2.56 (s, 3H), 2.29 (s, 3H), 1.47 (s, 9 H); m / z: 348. Example 85 The following compound was prepared by a process analogous to that used in the preparation of Example 84, using 2-methyl-1,3-thiazole-5-amine and the appropriate starting material.

Example 86 2-Chloro-N- (2-formyl-1,3-thiazol-5-yl) -5-. { r 3 (trifluoromethyl) benzoyl aminolbenzamide To a 25 ml round bottom flask loaded with a magnetic stir bar and 5 - [(2-chloro-5-. {[3- (tri-fluoro-methyl) -benzoyl] -amino)} benzoyl) amino] -N-methoxy-N-methyl-1,3-thiazole-2-carboxamide (0.28 g, 0.545 mmol) (Example 13) anhydrous THF (5 mL) was added. The reaction was cooled to 0 ° C and lithium aluminum hydride (0.03 g, 0.698 mmol) was added to the reaction mixture with stirring. The reaction mixture was stirred for 0.5 h before it was carefully diluted with a saturated aqueous solution of NH CI (-20 ml). The mixture was then poured into a separatory funnel and extracted with EtOAc (-50 mL). The organic phase was separated, dried with MgSO 4, filtered, and concentrated, in vacuo to give the title compound as a colorless oil which was used without further purification; m / z: 454. Examples 87 and 88 The following compounds were prepared by a process analogous to that described in Example 86, using the appropriate starting material.

Claims

1. A compound of formula (I): or an acceptable pharmaceutical salt thereof; where: A is, wherein Ring A is aryl, heteroaryl, carbocyclyl or heterocyclyl; wherein if the heterocyclyl contains an -NH- moiety the nitrogen may optionally be substituted by a group selected from R5; or A is alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, or alkynyl of 2 to 6 carbon atoms, wherein A can optionally be substituted on carbon by one or more R8; and wherein if the heterocyclyl contains a -NH-portion the nitrogen can optionally be substituted by a group selected from R9; R1 is a substituent on carbon and is selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl from 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N , N- (alkyl of 1 to 6 carbon atoms) 2-amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) carbon) 2carbamoyl, alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, alkoxycarbonylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2 sulfamoyl, N- (alkyl of 1 to 6 carbon atoms) -N- (alkoxy of 1 to 6 carbon atoms) sulfamoyl, N , N '- (alkyl d and 1 to 6 carbon atoms) 2ureido, N ', N' - (alkyl of 1 'to 6 carbon atoms) 2ureido, N- (alkyl of 1 to 6 carbon atoms) -N'N' - (alkyl of 1 to 6 carbon atoms) 2ureido, alkylsulfonylamino of 1 to 6 carbon atoms, carbocyclyl-R6- or heterocyclyl-R7-; wherein R1 can optionally be substituted on the carbon by one or more R8; and wherein if the heterocyclyl contains a -NH- moiety the nitrogen can optionally be substituted by a group selected from R9; n is selected from 0-4; wherein the values of R1 may be the same or different; X is absent or is O or NRa, where Ra is H or alkyl of 1 to 6 carbon atoms; R2 and R3 are independently selected from hydrogen, halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N, N - (alkyl of 1 to 6 carbon atoms) 2-amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-carbamoyl, alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N- ( alkyl having 1 to 6 carbon atoms) 2-sulfamoyl, alkylsulfonylamino having 1 to 6 carbon atoms, carbocyclyl-R 10- or heterocyclyl-R 11 -; wherein R2 can optionally be substituted on the carbon by one or more R12; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen can optionally be substituted by a selected group of R 3; R 4 is selected from halo, cyano, amino, carboxy, carbamoyl, mercapto, sulfamoyl, ureido, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N, N- (alkyl of 1 to 6 carbon atoms) carbon) 2-amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2carbamoyl, alkyl of 1 to 6 carbon atoms carbonS (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-sulphamoyl, alkylsulfonylamine of 1 to 6 carbon atoms, carbocyclyl-R 14- or heterocyclyl-R 15-; where R4 can optionally be substituted on the carbon by one or more R16; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen can optionally be substituted by a group selected from R17; m is selected from 0-2; wherein the values of R4 may be the same or different; R8- and R12 are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N, N- (alkyl of 1 to 6 carbon atoms) 2amino, N- (alkyl of 1 to 6 carbon atoms) -N- (alkoxy of 1 to 6 carbon atoms) amino, alkanoylamino of 1 to 6 carbon atoms, N - (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2carbamoyl, alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2, alkoxycarbonyl from 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2sulfamoyl, alkylsulfonylamine of 1 to 6 carbon atoms, carbocyclyl -R18- or heterocyclic il-R19-; wherein R8 and R12 independently of each other may optionally be substituted on the carbon with one or more R20; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen can optionally be replaced by a group selected from R21; R16 is selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms , alkoxy of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) amino, N, N- (alkyl of 1 to 6 carbon atoms) 2-amino, alkanoylamino of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2carbamoyl, alkyl of 1 to 6 carbon atoms (O) a wherein a is 0 to 2, alkoxycarbonyl of 1 to 6 carbon atoms, N- (alkyl of 1 to 6 carbon atoms) sulfamoyl, N, N- (alkyl of 1 to 6 carbon atoms) 2-sulfamoyl, alkylsulfonylamino of 1 to 6 carbon atoms, carbocyclyl-R22- or heterocyclyl-R23-; wherein R1 can optionally be substituted on the carbon by one or more R24; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen can optionally be substituted by a group selected from R25; R6, R7, R10, R11, R14, R15, R18, R19, R22 and R23 are independently selected from a direct bond, -O-, -N (R26) -, -C (O) -, -N (R27) C (O) -, -C (O) N (R28) -, -S (O) 8-, -SO2N (R29) -o -N (R30) SO2-; wherein R26, R27, R28, R29 and R30 are independently selected from hydrogen or alkyl of 1 to 6 carbon atoms and s is 0-2; R5, R9, R13, R17, R21 and R25 are independently selected from alkyl of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms, alkylsulfonyl of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms , carbamoyl, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, N, N- (alkyl of 1 to 6 carbon atoms) carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsulfonyl; R20 and R24 are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N -methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N, N-dimethylcarbamoyl, N, N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, phenyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl , methoxycarbonyl, ethoxycarbonyl, N-methylsulphamoyl, N-ethylsulphamoyl, N, N-dimethylsulphamoyl, N, N-diethylsulphamoyl or N-methyl-N-ethylsulphamoyl, wherein R20 and R24 can optionally be substituted on the carbon with one or more R50; and R in each case is independently selected from halo, hydroxy, cyano, and alkoxy of 1 to 6 carbon atoms.

2. A compound of formula (I), or a pharmaceutically acceptable salt thereof, according to claim 1, wherein: A is wherein Ring A is aryl, heteroaryl, carbocyclyl and heterocyclyl; wherein if the heteroaryl contains a -NH- moiety the nitrogen may optionally be substituted by a selected group of R5; or A is alkyl of 1 to 6 carbon atoms; wherein A can optionally be substituted on the carbon by one or more R8a; R5 is alkyl of 1 to 6 carbon atoms; R8a in each case is independently selected from halo, alkoxy of 1 to 6 carbon atoms, and carbocyclyl-R18-, wherein R8a may optionally be substituted on carbon by one or more R20; R18 is a direct link; and R20 is methyl.

3. A compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1 or 2, wherein X is absent is or O.

4. A compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-3, wherein R1 is a substituent on the carbon and is selected from halo, alkyl of 1 to 6 carbon atoms, and carbocyclyl-R6-; where R1 can optionally be substituted on the carbon by one 0 more R8; R6 is a direct link; and R6 in each case is independently selected from halo and cyano.

5. A compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-4, wherein R2 and R3 are independently selected from hydrogen, halo, alkyl, 1 to 6 carbon atoms.

6. A compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-5, wherein: R4 is selected from alkyl of 1 to 6 carbon atoms, N- (alkyl) 1 to 6 carbon atoms) carbamoyl, N- (alkyl of 1 to 6 carbon atoms) -N- (alkoxy of 1 to 6 carbon atoms) carbamoyl, carbocyclyl-R14- or heterocyclyl-R15-; where R4 can optionally be substituted on the carbon by one or more R 16 R14 is a direct link; R15 is -C (O) -; R16 in each case is independently selected from hydroxy, N- (alkyl of 1 to 6 carbon atoms) amino, N, N- (alkyl of 1 to 6 carbon atoms) 2-amino, carbocyclyl-R22- and heterocyclyl-R23-; wherein R16 can optionally be substituted on the carbon by one or more R24; and wherein if the heterocyclyl contains an -NH- moiety the nitrogen can optionally be substituted by a group selected from R25; R22 is -N (R26) -; R23 is a direct link; R24 in each case is independently selected from methyl, methoxy, dimethylamine, and cyclopropyl, wherein R2 can optionally be substituted on the carbon by one or more R50; R25 is alkyl of 1 to 6 carbon atoms; R26 is hydrogen; and R50 is hydroxy.

7. A compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-6, wherein m is selected from 0 and 1.

8. A compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-7, wherein n is selected from 0 to 2, wherein the values of R1 may be the same or different.

9. A compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein A is selected from 3- (1-cyano-1-methylethyl) phenyl, 3- (trifluoromethyl) phenyl, 3-chlorophenyl, 3,5-dimethylphenyl, 3-fluoro-5- (trifluoromethyl) phenyl, 3-chloro-5-fluorophenyl, 3-cyclopropyl-5-fluorophenyl, 3,4-dichlorophenyl, 3-cyclopropylphenyl, 3-methylphenyl, 3-methylcyclohexyl, 2,6-dichloropyridin-4-yl, cyclopentyl , 3,4-dimethylphenyl, 6-methylpyridin-2-yl, 3-chloropyridin-4-yl, 5-methylpyridin-3-yl, 1,5-dimethyl-1 H -pyrazol-3-yl, 5-methyl- 1 H-pyrazole-3-yl, 4-methylcyclohexyl, 3- (trifluoromethyl) cyclohexyl, 4,4-difluorocyclohexyl, 1-tert-butyl-5-methyl-1 H-pyrazol-3-yl, 1-isopropyl- 1 H-pyrazol-3-yl, butyl, 3-methylpentyl, 2-methylbutyl, 3-methylbutyl, .sec-butoxymethyl, cyclohexylmethyl, 2-methylprop-2-yl, (4-methylcyclodoxyl) methyl, but-2-yl , hex-2-ylo, cyclopropylmethyl, cyclopentylmethyl, and cyclohexyl (difluoro) methyl; X is absent or is O; R1 is a substituent on carbon and is selected from fluoro, chloro, methyl, trifluoromethyl, 2-cyanoprop-2-yl, and cyclopropyl; R2 is hydrogen; R3 is selected from chlorine and methyl; R 4 is selected from methyl, isopropyl, N-methylcarbamoyl, (4-methyl-piperazin-1-yl) methyl, morpholinecarbonyl, N-methyl-N-methoxycarbamate 1, hydroxymethyl, (dimethylamine) methyl, 1-hydroxy ethyl, piperidinomethyl, (methylamino) methyl, morpholm-4-ylmethyl, 2- (dimethylamine) etl, 1-azetidinylmethyl, (cyclobutylamino) methyl, [(cyclopropylmethyl) amino] methyl, [(2-methoxyethyl) methylamino] met 1, [4- (Hydroxymethyl) piperidin-1-yl] methyl, isopropyl, (cyclopropylamino) methylo, and cyclopropyl; m is selected from 0 and 1; and n is selected from 0 to 2, wherein the values of R1 may be the same or different.

10. A compound of formula (I), selected from the group consisting of: 5-. { [3- (1-cyano-1-methylethyl) benzoyl] amino} -2-methyl-N- (2-methyl-1,3-thiazol-5-yl) benzamide; 2-chloro-N-1,3-thiazol-5-yl-5-. { [3- (trifluoromethyl) benzoyl] amino} benzamide; 2-chloro-5 - [(3-chlorobenzoyl) amino] -N-1,3-thiazol-5-ylbenzamide; 2-Chloro-5 - [(3,5-dimethylbenzoyl) amino] -N-1,3-thiazol-5-ylbenzamide; 5-. { [3- (1-cyano-1-methylethyl) benzoyl] amino} -2-methyl-N-1,3-tiazol-5-ylbenzamide; 2-methyl-N- (2-methyl-1-1, 3-ti-azol-5-I) -5-. { [3- (trifluoromethyl I) benzoyl] amino} benzamide; 2-chloro-5 - [(3-chlorobenzoyl) amino] -N- (2-methyl-1,3-thiazole-5-i) b e n z a m a d; 2-Chloro-5 - [(3,5-dimethylbenzoyl) amino] -N- (2-methyl-1,3-thiazol-5-yl) benzamide; 2-chloro-N- (2-methyl-1-1, 3-thiazol-5-yl) -5-. { [3- (trifluoromethyl) benzoyl] amine} benzamide; 2-chloro-5-. { [3-fluoro-5- (trifluoromethyl) benzoyl] amino} -N- (2-methyl-1,3-thiazol-5-yl) benzamide; 5 - [(5- { [3- (1-cyano-1-methyl-1-yl) -benzoyl] -amino} -2-methyl-benzoyl) -amino] -N-methyl-1 , 3-thiazole-2-carboxamide; 5-. { [3-Fluoro-5- (tr, fluoro methyl) benzoyl] amino} -2-methyl-N- (2-methyl-1,3-thiazol-5-yl) benzamide; 5 - [(3-chloro-5-fluoro benzoyl) amino] -2-methyl-N- (2-methyl-1,3-thiazol-5-yl) benzamide; 5 - [(3-Cyclopropyl-5-fluorobenzoyl) amin or] -2-methyl-N- (2-methyl-1,3-thiazol-5-yl) benzamide; 5 - [(3-chlorobenzoyl) amino] -2-methyl-N- (2-methyl-1,3-thiazol-5-yl) benzamide; 5- [3,4-dichlorobenzoyl) amino] -2-methyl-N- (2-butyl-1,3-thiazol-5-yl) benzamide; 5 - [(3-Cyclopropylbenzoyl) amino] -2-methyl-N- (2-methyl-1,3-thiazol-5-yl) benzamide; 5 - [(3,5-dimethylbenzoyl) amino] -2-methyl-N- (2-methyl-1,3-thiazol-5-yl) benzamide; 2-methyl-5 - [(3-methylbenzoyl) amino] -N- (2-methyl-1,3-ti a -olol-5-yl) benzamide; 2,6-dichloro-N- (4-methyl-3. {[[(2-methyl-1,3-thiazol-5-yl) amino] carbonyl} phenyl) isonicotinamide; 2-methyl-5-. { [(3-methylcyclohexyl) carbonyl] amino} -N- (2-methyl-1,3-thiazol-5-yl) benzamide; 2-methyl-N- (2-methyl-1,3-thiazol-5-yl) -5- (pentanoylamino) benzamide; or 2-methyl-5 - [(4-methylhexanoyl) amino] -N- (2-methyl-1,3-thiazol-5-yl) benzamide.

11. A compound of formula (I) or a pharmaceutically acceptable salt thereof, according to any of claims 1-10, for use as a medicament.

12. The use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-10, in the manufacture of a medicament for use in the production of an inhibitory effect on the kinase. of CSF-1R in a warm-blooded animal such as man.

13. The use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-10, in the manufacture of a medicament for use in the production of an anticancer effect in an animal. of warm blood such as man.

The use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-10, in the manufacture of a medicament for use in the treatment of breast, ovarian tumors, bladder, cervical, endometrial, prostate, lung, kidney and pancreatic; hematologic malignancies including myelodysplastic syndrome, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma and chronic lymphocytic leukemia; and glioma, squamous cell carcinoma of the esophagus, malignant melanoma of the uvea and follicular lymphoma, in a warm-blooded animal such as man.

15. The use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, according to claim 1-10, in the manufacture of a medicament for use in the treatment of osteolysis associated with - tumors, osteoporosis including bone loss induced by ovariectomy, failure of the orthopedic implant, autoimmune disorders including systemic lupus erythematosus, arthritis including rheumatoid arthritis, osteoarthritis, renal inflammation and glomerulonephritis; inflammatory bowel disease; transplant rejection including renal and bone marrow allografts and skin xenograft, atherosclerosis, obesity, Alzheimer's disease and Langerhans cell histiocytosis, in a warm-blooded animal such as man.

16. A method for producing an inhibitory effect on the CSF-1R kinase in a warm-blooded animal, such as man, in need of such treatment, the method comprises administering to the animal an effective amount of a compound of formula (I). ), or a pharmaceutical salt thereof, according to any of claims 1-10.

17. A method for producing an anticancer effect in a warm-blooded animal such as man, in need of such treatment, the method comprises administering to the animal an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt of the same, in accordance with any of claims 1-10.

18. A method to treat breast, ovarian, bladder, cervical, endometrial, prostate, lung, kidney and pancreatic tumors; hematologic malignancies including myelodysplastic syndrome, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma and chronic lymphocytic leukemia; and glioma, squamous cell carcinoma of the esophagus, malignant melanoma of the uvea and follicular lymphoma, in a warm-blooded animal such as man, in need of such treatment, the method comprises administering to the animal an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-10.

19. A method to treat osteolysis associated with tumors, osteoporosis including ovariectomy-induced bone loss, orthopedic implant failure, autoimmune disorders including sistémic lupus erythematosus, arthritis including rheumatoid arthritis, osteoarthritis, renal inflammation and glomerulonephritis; inflammatory bowel disease; transplant rejection including renal and bone marrow allografts and skin xenograft, atherosclerosis, obesity, Alzheimer's and Langerhans cell histacytosis, in a warm-blooded animal such as man, in need of such treatment, the method comprises administering to the animal an effective amount of a compound of formula (I), or a pharmaceutical salt thereof, in accordance with any of claims 1-10.

20. A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-10, and at least one pharmaceutically acceptable carrier, diluent, or excipient.

21. A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-10, and at least one pharmaceutically acceptable diluent or carrier, for use in the production of an inhibitory effect on the CSF-1R kinase in a warm-blooded animal such as man.

22. A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-10, and at least one pharmaceutically acceptable diluent or carrier, for use in the production of an anticancer effect on a warm-blooded animal such as man.

23. A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-10, and at least one pharmaceutically acceptable diluent or carrier, for use in the treatment of breast, ovarian, bladder, cervical, endometrial, prostate, lung, kidney and pancreatic tumors; hematological malignancies including myelodysplastic syndrome, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma and chronic lymphocytic leukemia; and glioma, squamous cell carcinoma of the esophagus, malignant melanoma of the uvea, and follicular lymphoma, in a warm-blooded animal, such as man.

24. A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-10, and at least one pharmaceutically acceptable diluent or carrier, for use in the treatment Osteolysis associated with tumors, osteoporosis including ovariectomy-induced bone loss, failure of the orthopedic implant, autoimmune disorders including systemic lupus erythematosus, arthritis including rheumatoid arthritis, osteoarthritis, renal inflammation and glomerulonephritis; inflammatory bowel disease; transplant rejection including renal and bone marrow allografts and skin xenograft, atherosclerosis, obesity, Alzheimer's disease and Langerhans cell histiocytosis, in a warm-blooded animal such as man.

25. A compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-10, for use in the production of an inhibitory effect on the CSF-1R kinase in a blood animal. hot like man.

26. A compound of formula • (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-10, for use in the production of an anticancer effect in a warm-blooded animal such as man.

27. A compound of formula (I), or a pharmaceutically acceptable salt thereof, as 20 defendants in any of claims 1-10, for use in the treatment of breast, ovarian, bladder, cervical, endometrial, prostate, lung tumors , kidney and pancreatic; hematological malignancies including medelodisplastic syndrome, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma and chronic lymphocytic leukemia; and glioma, squamous cell carcinoma of the esophagus, malignant melanoma of the uvea and follicular lymphoma, in a warm-blooded animal, just like a man.

28. A compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any of claims 1-10, for use in the treatment of osteolysis associated with tumors, osteoporosis including bone loss induced by ovariectomy, fails of orthopedic implant, autoimmune disorders including systemic lupus erythematosus, arthritis including rheumatoid arthritis, osteoarthritis, renal inflammation and glomerulonephritis; inflammatory bowel disease; transplant rejection including renal and bone marrow allografts and skin xenograft, atherosclerosis, obesity, Alzheimer's disease and Langerhans cell histocytosis, in a warm-blooded animal.