SK2002002A3 - Novel integrin receptor antagonists - Google Patents
Novel integrin receptor antagonists Download PDFInfo
- Publication number
- SK2002002A3 SK2002002A3 SK200-2002A SK2002002A SK2002002A3 SK 2002002 A3 SK2002002 A3 SK 2002002A3 SK 2002002 A SK2002002 A SK 2002002A SK 2002002 A3 SK2002002 A3 SK 2002002A3
- Authority
- SK
- Slovakia
- Prior art keywords
- aryl
- optionally substituted
- alkyl
- branched
- unbranched
- Prior art date
Links
- 229940127449 Integrin Receptor Antagonists Drugs 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 105
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 97
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 84
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 77
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 54
- 108010044426 integrins Proteins 0.000 claims abstract description 42
- 102000006495 integrins Human genes 0.000 claims abstract description 42
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000001301 oxygen Substances 0.000 claims abstract description 15
- 239000011593 sulfur Substances 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract 8
- -1 -O -aryl Chemical group 0.000 claims description 422
- 229910052739 hydrogen Inorganic materials 0.000 claims description 86
- 239000001257 hydrogen Substances 0.000 claims description 77
- 229920006395 saturated elastomer Polymers 0.000 claims description 72
- 125000003118 aryl group Chemical group 0.000 claims description 64
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 62
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- 125000005842 heteroatom Chemical group 0.000 claims description 60
- 150000002431 hydrogen Chemical class 0.000 claims description 56
- 125000001072 heteroaryl group Chemical group 0.000 claims description 49
- 125000000623 heterocyclic group Chemical group 0.000 claims description 46
- 125000003107 substituted aryl group Chemical group 0.000 claims description 44
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 42
- 238000002360 preparation method Methods 0.000 claims description 33
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 31
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 31
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 24
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 239000003446 ligand Substances 0.000 claims description 16
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 12
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 229910052740 iodine Inorganic materials 0.000 claims description 11
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 125000002837 carbocyclic group Chemical group 0.000 claims description 9
- 230000004962 physiological condition Effects 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 7
- 230000036961 partial effect Effects 0.000 claims description 7
- 238000006467 substitution reaction Methods 0.000 claims description 7
- 230000033115 angiogenesis Effects 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 5
- 125000005275 alkylenearyl group Chemical group 0.000 claims description 5
- 239000006071 cream Substances 0.000 claims description 5
- 230000003993 interaction Effects 0.000 claims description 5
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 206010027476 Metastases Diseases 0.000 claims description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 230000009401 metastasis Effects 0.000 claims description 4
- 150000002829 nitrogen Chemical class 0.000 claims description 4
- 230000004614 tumor growth Effects 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000037147 Hypercalcaemia Diseases 0.000 claims description 3
- 201000002980 Hyperparathyroidism Diseases 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 208000003076 Osteolysis Diseases 0.000 claims description 3
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 238000002399 angioplasty Methods 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 230000000148 hypercalcaemia Effects 0.000 claims description 3
- 208000029791 lytic metastatic bone lesion Diseases 0.000 claims description 3
- 230000003211 malignant effect Effects 0.000 claims description 3
- 230000001394 metastastic effect Effects 0.000 claims description 3
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 3
- 206010062198 microangiopathy Diseases 0.000 claims description 3
- 239000000651 prodrug Substances 0.000 claims description 3
- 229940002612 prodrug Drugs 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 230000002792 vascular Effects 0.000 claims description 3
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 2
- 206010003178 Arterial thrombosis Diseases 0.000 claims description 2
- 208000010191 Osteitis Deformans Diseases 0.000 claims description 2
- 208000027868 Paget disease Diseases 0.000 claims description 2
- 208000033626 Renal failure acute Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 201000011040 acute kidney failure Diseases 0.000 claims description 2
- 208000012998 acute renal failure Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 208000027202 mammary Paget disease Diseases 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 230000003071 parasitic effect Effects 0.000 claims description 2
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical class [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 125000003367 polycyclic group Chemical group 0.000 claims description 2
- 125000006850 spacer group Chemical group 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims description 2
- 125000005647 linker group Chemical group 0.000 claims 2
- 208000035143 Bacterial infection Diseases 0.000 claims 1
- 208000030852 Parasitic disease Diseases 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 abstract 1
- 239000005977 Ethylene Substances 0.000 abstract 1
- 230000037431 insertion Effects 0.000 abstract 1
- 238000003780 insertion Methods 0.000 abstract 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 218
- 239000000203 mixture Substances 0.000 description 151
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 149
- 150000003254 radicals Chemical class 0.000 description 143
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 106
- 239000000460 chlorine Substances 0.000 description 97
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 90
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 73
- 238000003786 synthesis reaction Methods 0.000 description 73
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 72
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 68
- 230000015572 biosynthetic process Effects 0.000 description 66
- 238000006243 chemical reaction Methods 0.000 description 64
- 239000000243 solution Substances 0.000 description 53
- 229960000583 acetic acid Drugs 0.000 description 51
- 235000011054 acetic acid Nutrition 0.000 description 49
- 239000012043 crude product Substances 0.000 description 49
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- 238000005160 1H NMR spectroscopy Methods 0.000 description 43
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 42
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 39
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 37
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- 239000007787 solid Substances 0.000 description 35
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
- 238000003776 cleavage reaction Methods 0.000 description 31
- 230000007017 scission Effects 0.000 description 31
- VZUXWUCCOZOSBE-UHFFFAOYSA-N 1h-azepin-4-yl acetate Chemical compound CC(=O)OC1=CC=CNC=C1 VZUXWUCCOZOSBE-UHFFFAOYSA-N 0.000 description 30
- 150000004702 methyl esters Chemical class 0.000 description 30
- 238000000746 purification Methods 0.000 description 29
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 150000001412 amines Chemical group 0.000 description 27
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 27
- 230000007062 hydrolysis Effects 0.000 description 27
- 238000006460 hydrolysis reaction Methods 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 238000010898 silica gel chromatography Methods 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- 239000003921 oil Substances 0.000 description 23
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 21
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 21
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 20
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
- 239000002244 precipitate Substances 0.000 description 19
- 238000000034 method Methods 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- 238000001704 evaporation Methods 0.000 description 15
- 230000008020 evaporation Effects 0.000 description 15
- 125000006239 protecting group Chemical group 0.000 description 15
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 14
- 238000001035 drying Methods 0.000 description 14
- MZMVGIGYBXZUEI-UHFFFAOYSA-N methyl 2-(5-acetyloxy-6-oxo-11h-benzo[c][1]benzazepin-11-yl)acetate Chemical compound CC(=O)ON1C(=O)C2=CC=CC=C2C(CC(=O)OC)C2=CC=CC=C21 MZMVGIGYBXZUEI-UHFFFAOYSA-N 0.000 description 14
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 239000004793 Polystyrene Substances 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 13
- 238000010626 work up procedure Methods 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 10
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- 239000012442 inert solvent Substances 0.000 description 10
- YDNLNVZZTACNJX-UHFFFAOYSA-N isocyanatomethylbenzene Chemical compound O=C=NCC1=CC=CC=C1 YDNLNVZZTACNJX-UHFFFAOYSA-N 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- ADULVLOFPKPAHD-UHFFFAOYSA-N (1-pyridin-2-ylpiperidin-4-yl)methanamine Chemical compound C1CC(CN)CCN1C1=CC=CC=N1 ADULVLOFPKPAHD-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- DUAAOKLOZOSUNV-UHFFFAOYSA-N n-[4-(aminomethyl)phenyl]-1h-benzimidazol-2-amine;hydrochloride Chemical compound Cl.C1=CC(CN)=CC=C1NC1=NC2=CC=CC=C2N1 DUAAOKLOZOSUNV-UHFFFAOYSA-N 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- UAKVJGPANGBRHC-UHFFFAOYSA-N 1-[4-(aminomethyl)phenyl]-3-benzylurea;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(CN)=CC=C1NC(=O)NCC1=CC=CC=C1 UAKVJGPANGBRHC-UHFFFAOYSA-N 0.000 description 8
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 8
- 239000007821 HATU Substances 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 239000005557 antagonist Substances 0.000 description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 229910052731 fluorine Inorganic materials 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 238000005984 hydrogenation reaction Methods 0.000 description 7
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- RKZTVVDAJQDROO-UHFFFAOYSA-N tert-butyl 2-(6-oxo-5,11-dihydrobenzo[c][1]benzazepin-11-yl)acetate Chemical compound N1C(=O)C2=CC=CC=C2C(CC(=O)OC(C)(C)C)C2=CC=CC=C21 RKZTVVDAJQDROO-UHFFFAOYSA-N 0.000 description 7
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- UNTPRMVENFEMSP-UHFFFAOYSA-N 2-[4-(aminomethyl)-1,3-thiazol-2-yl]guanidine dihydrochloride Chemical compound Cl.Cl.NCC1=CSC(NC(N)=N)=N1 UNTPRMVENFEMSP-UHFFFAOYSA-N 0.000 description 6
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 6
- DKSXUNKSOYNTRR-UHFFFAOYSA-N 4H-azepin-5-yl acetate Chemical compound C(C)(=O)OC1=CC=NC=CC1 DKSXUNKSOYNTRR-UHFFFAOYSA-N 0.000 description 6
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 6
- 150000001298 alcohols Chemical class 0.000 description 6
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- LHECUOWWTZDOOS-UHFFFAOYSA-N methyl 3-(5-acetyloxy-6-oxo-11h-benzo[c][1]benzazepin-11-yl)propanoate Chemical compound CC(=O)ON1C(=O)C2=CC=CC=C2C(CCC(=O)OC)C2=CC=CC=C21 LHECUOWWTZDOOS-UHFFFAOYSA-N 0.000 description 6
- 238000010647 peptide synthesis reaction Methods 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 5
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 5
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 5
- MTAODLNXWYIKSO-UHFFFAOYSA-N 2-fluoropyridine Chemical compound FC1=CC=CC=N1 MTAODLNXWYIKSO-UHFFFAOYSA-N 0.000 description 5
- PSKARDOKSNTQHC-UHFFFAOYSA-N 3-[11-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-6-oxo-11h-benzo[c][1]benzazepin-5-yl]propanoic acid Chemical compound OC(=O)CCN1C(=O)C2=CC=CC=C2C(CC(=O)OC(C)(C)C)C2=CC=CC=C21 PSKARDOKSNTQHC-UHFFFAOYSA-N 0.000 description 5
- 125000006050 3-methyl-2-pentenyl group Chemical group 0.000 description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
- 239000000370 acceptor Substances 0.000 description 5
- 230000029936 alkylation Effects 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- GTCAXTIRRLKXRU-UHFFFAOYSA-N carbamic acid methyl ester Natural products COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 150000002170 ethers Chemical class 0.000 description 5
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 5
- 239000006260 foam Substances 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 239000012452 mother liquor Substances 0.000 description 5
- 150000002828 nitro derivatives Chemical class 0.000 description 5
- 102000013415 peroxidase activity proteins Human genes 0.000 description 5
- 108040007629 peroxidase activity proteins Proteins 0.000 description 5
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 5
- 229920002554 vinyl polymer Polymers 0.000 description 5
- VZPQXXZCGBYDKX-UHFFFAOYSA-N 1-(1h-benzimidazol-2-yl)pentane-1,5-diamine;hydrochloride Chemical compound Cl.C1=CC=C2NC(C(N)CCCCN)=NC2=C1 VZPQXXZCGBYDKX-UHFFFAOYSA-N 0.000 description 4
- GVKCMDVUXSQDJY-UHFFFAOYSA-N 2-[5-(aminomethyl)-1,3-thiazol-2-yl]guanidine;dihydrochloride Chemical compound Cl.Cl.NCC1=CN=C(NC(N)=N)S1 GVKCMDVUXSQDJY-UHFFFAOYSA-N 0.000 description 4
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 4
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- HWHLOILPNVNHJW-UHFFFAOYSA-N 3-amino-n-(1h-imidazol-2-yl)propanamide Chemical compound NCCC(=O)NC1=NC=CN1 HWHLOILPNVNHJW-UHFFFAOYSA-N 0.000 description 4
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 4
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 4
- MZRGNMWEURVQHC-UHFFFAOYSA-N 4-(aminomethyl)-n-benzylpiperidine-1-carboxamide Chemical compound C1CC(CN)CCN1C(=O)NCC1=CC=CC=C1 MZRGNMWEURVQHC-UHFFFAOYSA-N 0.000 description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 4
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 4
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- HYYCRJMQSAHCEA-UHFFFAOYSA-N Cl.C1=CC(CN)=CC=C1NC(=O)CCC1=CC=CC=C1 Chemical compound Cl.C1=CC(CN)=CC=C1NC(=O)CCC1=CC=CC=C1 HYYCRJMQSAHCEA-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- XIGLAGCWUMEXAW-UHFFFAOYSA-N FC(C(=O)O)(F)F.CC1=CC2=C(NC(=N2)C2=CC=C(C=C2)CN)C=C1C Chemical compound FC(C(=O)O)(F)F.CC1=CC2=C(NC(=N2)C2=CC=C(C=C2)CN)C=C1C XIGLAGCWUMEXAW-UHFFFAOYSA-N 0.000 description 4
- XWTFRDDFWWCLRL-UHFFFAOYSA-N FC(C(=O)O)(F)F.ClC1=CC2=C(NC(=N2)C2=CC=C(C=C2)CN)C=C1 Chemical compound FC(C(=O)O)(F)F.ClC1=CC2=C(NC(=N2)C2=CC=C(C=C2)CN)C=C1 XWTFRDDFWWCLRL-UHFFFAOYSA-N 0.000 description 4
- 108010049003 Fibrinogen Proteins 0.000 description 4
- 102000008946 Fibrinogen Human genes 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- 229920001213 Polysorbate 20 Polymers 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 150000001340 alkali metals Chemical class 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 150000001450 anions Chemical class 0.000 description 4
- RIIWUGSYXOBDMC-UHFFFAOYSA-N benzene-1,2-diamine;hydron;dichloride Chemical compound Cl.Cl.NC1=CC=CC=C1N RIIWUGSYXOBDMC-UHFFFAOYSA-N 0.000 description 4
- VQBSBPWUNQCZST-UHFFFAOYSA-N benzyl n-[4-(aminomethyl)phenyl]carbamate;hydrochloride Chemical compound Cl.C1=CC(CN)=CC=C1NC(=O)OCC1=CC=CC=C1 VQBSBPWUNQCZST-UHFFFAOYSA-N 0.000 description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 239000007822 coupling agent Substances 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- MVGGJHQSJMZKLW-UHFFFAOYSA-N ethyl 3-[11-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-6-oxo-11h-benzo[c][1]benzazepin-5-yl]propanoate Chemical compound O=C1N(CCC(=O)OCC)C2=CC=CC=C2C(CC(=O)OC(C)(C)C)C2=CC=CC=C21 MVGGJHQSJMZKLW-UHFFFAOYSA-N 0.000 description 4
- 229940012952 fibrinogen Drugs 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- VMTXAWDRBQJBOQ-UHFFFAOYSA-N n-[[4-(aminomethyl)phenyl]methyl]pyridin-2-amine Chemical compound C1=CC(CN)=CC=C1CNC1=CC=CC=N1 VMTXAWDRBQJBOQ-UHFFFAOYSA-N 0.000 description 4
- XUXVOYJNGYUAOR-UHFFFAOYSA-N n-[[5-(aminomethyl)thiophen-3-yl]methyl]pyridin-2-amine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.S1C(CN)=CC(CNC=2N=CC=CC=2)=C1 XUXVOYJNGYUAOR-UHFFFAOYSA-N 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 4
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 4
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- 238000001665 trituration Methods 0.000 description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 3
- 125000006079 1,1,2-trimethyl-2-propenyl group Chemical group 0.000 description 3
- 125000006059 1,1-dimethyl-2-butenyl group Chemical group 0.000 description 3
- 125000006033 1,1-dimethyl-2-propenyl group Chemical group 0.000 description 3
- 125000006060 1,1-dimethyl-3-butenyl group Chemical group 0.000 description 3
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- 125000006062 1,2-dimethyl-2-butenyl group Chemical group 0.000 description 3
- 125000006035 1,2-dimethyl-2-propenyl group Chemical group 0.000 description 3
- 125000006063 1,2-dimethyl-3-butenyl group Chemical group 0.000 description 3
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 3
- 125000006065 1,3-dimethyl-2-butenyl group Chemical group 0.000 description 3
- 125000006066 1,3-dimethyl-3-butenyl group Chemical group 0.000 description 3
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 3
- 125000006074 1-ethyl-2-butenyl group Chemical group 0.000 description 3
- 125000006082 1-ethyl-2-methyl-2-propenyl group Chemical group 0.000 description 3
- 125000006037 1-ethyl-2-propenyl group Chemical group 0.000 description 3
- 125000006075 1-ethyl-3-butenyl group Chemical group 0.000 description 3
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000006028 1-methyl-2-butenyl group Chemical group 0.000 description 3
- 125000006048 1-methyl-2-pentenyl group Chemical group 0.000 description 3
- 125000006021 1-methyl-2-propenyl group Chemical group 0.000 description 3
- 125000006030 1-methyl-3-butenyl group Chemical group 0.000 description 3
- 125000006055 1-methyl-4-pentenyl group Chemical group 0.000 description 3
- 125000006067 2,2-dimethyl-3-butenyl group Chemical group 0.000 description 3
- 125000006069 2,3-dimethyl-2-butenyl group Chemical group 0.000 description 3
- 125000006070 2,3-dimethyl-3-butenyl group Chemical group 0.000 description 3
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 3
- 125000006077 2-ethyl-2-butenyl group Chemical group 0.000 description 3
- 125000006078 2-ethyl-3-butenyl group Chemical group 0.000 description 3
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000006040 2-hexenyl group Chemical group 0.000 description 3
- 125000006029 2-methyl-2-butenyl group Chemical group 0.000 description 3
- 125000006049 2-methyl-2-pentenyl group Chemical group 0.000 description 3
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 3
- 125000006031 2-methyl-3-butenyl group Chemical group 0.000 description 3
- 125000006056 2-methyl-4-pentenyl group Chemical group 0.000 description 3
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 3
- 125000006024 2-pentenyl group Chemical group 0.000 description 3
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 3
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 3
- 125000006041 3-hexenyl group Chemical group 0.000 description 3
- 125000006032 3-methyl-3-butenyl group Chemical group 0.000 description 3
- 125000006054 3-methyl-3-pentenyl group Chemical group 0.000 description 3
- 125000006057 3-methyl-4-pentenyl group Chemical group 0.000 description 3
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 3
- 125000006042 4-hexenyl group Chemical group 0.000 description 3
- 125000006051 4-methyl-2-pentenyl group Chemical group 0.000 description 3
- 125000003119 4-methyl-3-pentenyl group Chemical group [H]\C(=C(/C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000006058 4-methyl-4-pentenyl group Chemical group 0.000 description 3
- FHYNZXSHHPBOBK-UHFFFAOYSA-N 5-(aminomethyl)thiophene-2-carbonitrile Chemical compound NCC1=CC=C(C#N)S1 FHYNZXSHHPBOBK-UHFFFAOYSA-N 0.000 description 3
- OSDGTEZAPBYUQX-UHFFFAOYSA-N 5-(aminomethyl)thiophene-3-carbonitrile Chemical compound NCC1=CC(C#N)=CS1 OSDGTEZAPBYUQX-UHFFFAOYSA-N 0.000 description 3
- 125000006043 5-hexenyl group Chemical group 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- RUKRZRYCLGTPTP-UHFFFAOYSA-N Cl.Cl.NCC1=CSC(NC=2N=CC=CC=2)=N1 Chemical compound Cl.Cl.NCC1=CSC(NC=2N=CC=CC=2)=N1 RUKRZRYCLGTPTP-UHFFFAOYSA-N 0.000 description 3
- IADOSIYGNMDNPP-UHFFFAOYSA-N Cl.Cl.S1C(CN)=CN=C1NC1=CC=CC=N1 Chemical compound Cl.Cl.S1C(CN)=CN=C1NC1=CC=CC=N1 IADOSIYGNMDNPP-UHFFFAOYSA-N 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 3
- 108010031318 Vitronectin Proteins 0.000 description 3
- 102100035140 Vitronectin Human genes 0.000 description 3
- HHTYRBUNKQWNLD-UHFFFAOYSA-N [5-[2-[[6-(1h-benzimidazol-2-yl)pyridin-3-yl]methylamino]-2-oxoethyl]-6-oxo-11h-benzo[c][1]benzazepin-11-yl] acetate Chemical compound O=C1C2=CC=CC=C2C(OC(=O)C)C2=CC=CC=C2N1CC(=O)NCC1=CC=C(C=2NC3=CC=CC=C3N=2)N=C1 HHTYRBUNKQWNLD-UHFFFAOYSA-N 0.000 description 3
- BTQNFCHSVJBKHV-UHFFFAOYSA-N [5-oxo-6-[2-oxo-2-[[4-[(pyridin-2-ylamino)methyl]phenyl]methylamino]ethyl]-6,11-dihydrodibenzo[2,1-b:2',1'-e][7]annulen-11-yl] acetate Chemical compound O=C1C2=CC=CC=C2C(OC(=O)C)C2=CC=CC=C2C1CC(=O)NCC(C=C1)=CC=C1CNC1=CC=CC=N1 BTQNFCHSVJBKHV-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 150000001342 alkaline earth metals Chemical class 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- RJNJWHFSKNJCTB-UHFFFAOYSA-N benzylurea Chemical compound NC(=O)NCC1=CC=CC=C1 RJNJWHFSKNJCTB-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 235000013877 carbamide Nutrition 0.000 description 3
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 238000007327 hydrogenolysis reaction Methods 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- GLQTZPSKNCLNQG-UHFFFAOYSA-N n'-(1h-benzimidazol-2-yl)butane-1,4-diamine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=C2NC(NCCCCN)=NC2=C1 GLQTZPSKNCLNQG-UHFFFAOYSA-N 0.000 description 3
- CNDAFPBECHAXDU-UHFFFAOYSA-N n'-pyridin-2-ylpropane-1,3-diamine Chemical compound NCCCNC1=CC=CC=N1 CNDAFPBECHAXDU-UHFFFAOYSA-N 0.000 description 3
- BTEUQJUOWGXDJC-UHFFFAOYSA-N n-[4-(aminomethyl)phenyl]pyridin-2-amine Chemical compound C1=CC(CN)=CC=C1NC1=CC=CC=N1 BTEUQJUOWGXDJC-UHFFFAOYSA-N 0.000 description 3
- SBSLCPHONZWKIE-UHFFFAOYSA-N n-piperidin-4-ylpyridin-2-amine Chemical compound C1CNCCC1NC1=CC=CC=N1 SBSLCPHONZWKIE-UHFFFAOYSA-N 0.000 description 3
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 3
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 210000002997 osteoclast Anatomy 0.000 description 3
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 235000008476 powdered milk Nutrition 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 3
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 3
- 125000004941 pyridazin-5-yl group Chemical group N1=NC=CC(=C1)* 0.000 description 3
- 125000004942 pyridazin-6-yl group Chemical group N1=NC=CC=C1* 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 3
- 150000003462 sulfoxides Chemical class 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 3
- WRAOGDJKTDDORV-UHFFFAOYSA-N tert-butyl n-(1h-benzimidazol-2-ylmethyl)carbamate Chemical compound C1=CC=C2NC(CNC(=O)OC(C)(C)C)=NC2=C1 WRAOGDJKTDDORV-UHFFFAOYSA-N 0.000 description 3
- UXWQXBSQQHAGMG-UHFFFAOYSA-N tert-butyl n-[(4-aminophenyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(N)C=C1 UXWQXBSQQHAGMG-UHFFFAOYSA-N 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 3
- 125000004306 triazinyl group Chemical group 0.000 description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- 125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 description 2
- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 description 2
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 2
- 125000006080 1-ethyl-1-methyl-2-propenyl group Chemical group 0.000 description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
- XPFSMDZLNJRDNP-UHFFFAOYSA-N 1h-azepine-2,5-dione Chemical class O=C1C=CNC(=O)C=C1 XPFSMDZLNJRDNP-UHFFFAOYSA-N 0.000 description 2
- AZJGOLHFNVIVMO-UHFFFAOYSA-N 2-(3-bromo-2-oxopropyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CC(=O)CBr)C(=O)C2=C1 AZJGOLHFNVIVMO-UHFFFAOYSA-N 0.000 description 2
- IHXURFIRYDRFTJ-UHFFFAOYSA-N 2-[4-(aminomethyl)phenyl]guanidine;dihydrochloride Chemical compound Cl.Cl.NCC1=CC=C(NC(N)=N)C=C1 IHXURFIRYDRFTJ-UHFFFAOYSA-N 0.000 description 2
- HSECRTCXKIVWPZ-UHFFFAOYSA-N 2-[5-[2-(3h-imidazo[4,5-b]pyridin-3-ium-2-ylmethylamino)-2-oxoethyl]-6-oxo-11h-benzo[c][1]benzazepin-11-yl]acetic acid;acetate Chemical compound CC([O-])=O.O=C1C2=CC=CC=C2C(CC(=O)O)C2=CC=CC=C2N1CC(=O)NCC1=NC2=CC=CN=C2[NH2+]1 HSECRTCXKIVWPZ-UHFFFAOYSA-N 0.000 description 2
- MOXPXJYZTWAWIQ-UHFFFAOYSA-N 2-[5-[2-[[4-(1h-benzimidazol-2-yl)phenyl]methylamino]-2-oxoethyl]-6-oxo-11h-benzo[c][1]benzazepin-11-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)C2=CC=CC=C2N1CC(=O)NCC1=CC=C(C=2NC3=CC=CC=C3N=2)C=C1 MOXPXJYZTWAWIQ-UHFFFAOYSA-N 0.000 description 2
- OFQVIPNTUUYFQG-UHFFFAOYSA-N 2-[6-oxo-5-[2-oxo-2-[4-[(pyridin-1-ium-2-ylamino)methyl]piperidin-1-yl]ethyl]-11h-benzo[c][1]benzazepin-11-yl]acetic acid;acetate Chemical compound CC([O-])=O.O=C1C2=CC=CC=C2C(CC(=O)O)C2=CC=CC=C2N1CC(=O)N(CC1)CCC1CNC1=CC=CC=[NH+]1 OFQVIPNTUUYFQG-UHFFFAOYSA-N 0.000 description 2
- WJJFQCIJYSHIPM-UHFFFAOYSA-N 2-[[11-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-6-oxo-11h-benzo[c][1]benzazepin-5-yl]methyl]-1,3-thiazole-4-carboxylic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)OC(C)(C)C)C2=CC=CC=C2N1CC1=NC(C(O)=O)=CS1 WJJFQCIJYSHIPM-UHFFFAOYSA-N 0.000 description 2
- YDAJTAXOUBOGHM-UHFFFAOYSA-N 2-chloro-3-(1,3-dioxoisoindol-2-yl)propanal Chemical compound C1=CC=C2C(=O)N(CC(Cl)C=O)C(=O)C2=C1 YDAJTAXOUBOGHM-UHFFFAOYSA-N 0.000 description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
- BFWYZZPDZZGSLJ-UHFFFAOYSA-N 4-(aminomethyl)aniline Chemical compound NCC1=CC=C(N)C=C1 BFWYZZPDZZGSLJ-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 102100021267 Anion exchange protein 4 Human genes 0.000 description 2
- 101710160272 Anion exchange protein 4 Proteins 0.000 description 2
- 208000006386 Bone Resorption Diseases 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 241001325266 Cordia Species 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- XLXVSFQMQLJRPE-UHFFFAOYSA-N FC(C(=O)O)(F)F.N1C(=NC2=C1C=CC=C2)C=2C=C(SC2)CN Chemical compound FC(C(=O)O)(F)F.N1C(=NC2=C1C=CC=C2)C=2C=C(SC2)CN XLXVSFQMQLJRPE-UHFFFAOYSA-N 0.000 description 2
- LCAICSZQCTWKEU-UHFFFAOYSA-N FC(C(=O)O)(F)F.N1CC(CC1)CCNC1=NC=CC=C1 Chemical compound FC(C(=O)O)(F)F.N1CC(CC1)CCNC1=NC=CC=C1 LCAICSZQCTWKEU-UHFFFAOYSA-N 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 206010029113 Neovascularisation Diseases 0.000 description 2
- NEMUHXJNPBHMST-UHFFFAOYSA-N OC(=O)C(F)(F)F.C=1C=CC=NC=1NCCC1CCNCC1 Chemical compound OC(=O)C(F)(F)F.C=1C=CC=NC=1NCCC1CCNCC1 NEMUHXJNPBHMST-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108060008245 Thrombospondin Proteins 0.000 description 2
- 102000002938 Thrombospondin Human genes 0.000 description 2
- 208000024248 Vascular System injury Diseases 0.000 description 2
- 208000012339 Vascular injury Diseases 0.000 description 2
- PKLJPUNEKPKIEE-UHFFFAOYSA-N [5-(1h-benzimidazol-2-yl)thiophen-2-yl]methanamine Chemical compound S1C(CN)=CC=C1C1=NC2=CC=CC=C2N1 PKLJPUNEKPKIEE-UHFFFAOYSA-N 0.000 description 2
- FRBWTRHDRCAYKM-UHFFFAOYSA-N [6-(1h-benzimidazol-2-yl)pyridin-3-yl]methanamine Chemical compound N1=CC(CN)=CC=C1C1=NC2=CC=CC=C2N1 FRBWTRHDRCAYKM-UHFFFAOYSA-N 0.000 description 2
- ARGKOKXPYKQFDX-UHFFFAOYSA-N [6-oxo-5-[2-oxo-2-[(1-pyridin-2-ylpiperidin-4-yl)methylamino]ethyl]-11h-benzo[c][1]benzazepin-11-yl] acetate Chemical compound O=C1C2=CC=CC=C2C(OC(=O)C)C2=CC=CC=C2N1CC(=O)NCC(CC1)CCN1C1=CC=CC=N1 ARGKOKXPYKQFDX-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- HSFYVXNQCIPVDL-UHFFFAOYSA-N acetic acid 1-N-pyridin-2-ylpropane-1,2-diamine Chemical compound C(C)(=O)O.CC(CNC1=NC=CC=C1)N HSFYVXNQCIPVDL-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
- 125000006242 amine protecting group Chemical group 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000002141 anti-parasite Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000003096 antiparasitic agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000005840 aryl radicals Chemical class 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- MDKCFLQDBWCQCV-UHFFFAOYSA-N benzyl isothiocyanate Chemical compound S=C=NCC1=CC=CC=C1 MDKCFLQDBWCQCV-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000002805 bone matrix Anatomy 0.000 description 2
- 230000024279 bone resorption Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 150000001723 carbon free-radicals Chemical class 0.000 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
- 230000035605 chemotaxis Effects 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 210000003711 chorioallantoic membrane Anatomy 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 2
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 150000002240 furans Chemical class 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N hydroxylamine hydrochloride Substances Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- WCYJQVALWQMJGE-UHFFFAOYSA-M hydroxylammonium chloride Chemical compound [Cl-].O[NH3+] WCYJQVALWQMJGE-UHFFFAOYSA-M 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- NUWHJBMLLFOCTQ-UHFFFAOYSA-N methyl 2-(5-acetyloxy-4-oxo-10h-thieno[3,4-c][1]benzazepin-10-yl)acetate Chemical compound O=C1N(OC(C)=O)C2=CC=CC=C2C(CC(=O)OC)C2=CSC=C21 NUWHJBMLLFOCTQ-UHFFFAOYSA-N 0.000 description 2
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 2
- YOCAAJWJOKWKDJ-UHFFFAOYSA-N methylcarbamic acid;2,2,2-trifluoroacetic acid Chemical compound CNC(O)=O.OC(=O)C(F)(F)F YOCAAJWJOKWKDJ-UHFFFAOYSA-N 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 2
- JUXGQFSDTCOTLI-UHFFFAOYSA-N n-(piperidin-4-ylmethyl)-1h-benzimidazol-2-amine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2NC=1NCC1CCNCC1 JUXGQFSDTCOTLI-UHFFFAOYSA-N 0.000 description 2
- 230000008692 neointimal formation Effects 0.000 description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
- 229910000510 noble metal Inorganic materials 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- NZCRJKRKKOLAOJ-XRCRFVBUSA-N rifaximin Chemical compound OC1=C(C(O)=C2C)C3=C4N=C5C=C(C)C=CN5C4=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O NZCRJKRKKOLAOJ-XRCRFVBUSA-N 0.000 description 2
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000008259 solid foam Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- KLKBCNDBOVRQIJ-UHFFFAOYSA-N tert-butyl 4-(aminomethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CN)CC1 KLKBCNDBOVRQIJ-UHFFFAOYSA-N 0.000 description 2
- SMZKPZXYDDZDJG-UHFFFAOYSA-N tert-butyl n-(cyanomethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC#N SMZKPZXYDDZDJG-UHFFFAOYSA-N 0.000 description 2
- AICNOYKJROIDHS-UHFFFAOYSA-N tert-butyl n-[[4-(1h-benzimidazol-2-yl)-1,3-thiazol-2-yl]methyl]carbamate Chemical compound S1C(CNC(=O)OC(C)(C)C)=NC(C=2NC3=CC=CC=C3N=2)=C1 AICNOYKJROIDHS-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 108010047303 von Willebrand Factor Proteins 0.000 description 2
- 102100036537 von Willebrand factor Human genes 0.000 description 2
- 229960001134 von willebrand factor Drugs 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- ZRVZOBGMZWVJOS-VMXHOPILSA-N (2s)-6-amino-2-[[(2s)-1-[(2s)-2-[[(2s)-2-[[2-[[(2s)-2-[(2-aminoacetyl)amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]hexanoic acid Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC(=O)CN ZRVZOBGMZWVJOS-VMXHOPILSA-N 0.000 description 1
- CIUYJYRQKYGNQP-UHFFFAOYSA-N (3-nitrophenyl)methanamine Chemical compound NCC1=CC=CC([N+]([O-])=O)=C1 CIUYJYRQKYGNQP-UHFFFAOYSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 1
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
- FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
- 125000004711 1,1-dimethylethylthio group Chemical group CC(C)(S*)C 0.000 description 1
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- YJUUZFWMKJBVFJ-UHFFFAOYSA-N 1,3-dimethylimidazolidin-4-one Chemical compound CN1CN(C)C(=O)C1 YJUUZFWMKJBVFJ-UHFFFAOYSA-N 0.000 description 1
- WXLCDTBTIVJDCE-UHFFFAOYSA-N 1,4-oxazepine Chemical class O1C=CC=NC=C1 WXLCDTBTIVJDCE-UHFFFAOYSA-N 0.000 description 1
- CUSVCHKYDIMHSV-UHFFFAOYSA-N 1-(4,5-dihydro-1h-imidazol-2-yl)ethane-1,2-diamine Chemical compound NCC(N)C1=NCCN1 CUSVCHKYDIMHSV-UHFFFAOYSA-N 0.000 description 1
- NPOGYZSRMJCBDM-UHFFFAOYSA-N 1-[3-(aminomethyl)phenyl]-3-benzylurea hydrochloride Chemical compound Cl.NCC1=CC=CC(NC(=O)NCC=2C=CC=CC=2)=C1 NPOGYZSRMJCBDM-UHFFFAOYSA-N 0.000 description 1
- DJYSTJVUSIEPJB-UHFFFAOYSA-N 1-[4-(aminomethyl)-1,3-thiazol-2-yl]-3-benzylurea hydrochloride Chemical compound Cl.NCC1=CSC(NC(=O)NCC=2C=CC=CC=2)=N1 DJYSTJVUSIEPJB-UHFFFAOYSA-N 0.000 description 1
- UYFRYGMDVFATIR-UHFFFAOYSA-N 1-[[4-(aminomethyl)phenyl]methyl]-3-benzylurea Chemical compound C1=CC(CN)=CC=C1CNC(=O)NCC1=CC=CC=C1 UYFRYGMDVFATIR-UHFFFAOYSA-N 0.000 description 1
- CGRMVCNMFASXPX-UHFFFAOYSA-N 1-benzyl-3-[4-[(1,3-dioxoisoindol-2-yl)methyl]-1,3-thiazol-2-yl]urea Chemical compound N=1C(CN2C(C3=CC=CC=C3C2=O)=O)=CSC=1NC(=O)NCC1=CC=CC=C1 CGRMVCNMFASXPX-UHFFFAOYSA-N 0.000 description 1
- JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 1
- COSJCAMRRQYRRD-UHFFFAOYSA-N 1-pyridin-2-ylethane-1,2-diamine Chemical compound NCC(N)C1=CC=CC=N1 COSJCAMRRQYRRD-UHFFFAOYSA-N 0.000 description 1
- DBVSTACDKGPBFJ-UHFFFAOYSA-N 1-pyridin-2-ylpropane-1,3-diamine Chemical compound NCCC(N)C1=CC=CC=N1 DBVSTACDKGPBFJ-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- UCOSRTUSVXHIMK-UHFFFAOYSA-N 1h-benzimidazol-2-ylmethanamine Chemical compound C1=CC=C2NC(CN)=NC2=C1 UCOSRTUSVXHIMK-UHFFFAOYSA-N 0.000 description 1
- XCTNDJAFNBCVOM-UHFFFAOYSA-N 1h-imidazo[4,5-b]pyridin-2-ylmethanamine Chemical compound C1=CC=C2NC(CN)=NC2=N1 XCTNDJAFNBCVOM-UHFFFAOYSA-N 0.000 description 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
- WFXGQJOEUFPLFV-UHFFFAOYSA-N 2-(1-bromopropan-2-yl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(C(CBr)C)C(=O)C2=C1 WFXGQJOEUFPLFV-UHFFFAOYSA-N 0.000 description 1
- YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 description 1
- QKVHAKICMNABGB-UHFFFAOYSA-N 2-(5-bromopentyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCCCBr)C(=O)C2=C1 QKVHAKICMNABGB-UHFFFAOYSA-N 0.000 description 1
- TVPJJKGFBGKYGU-UHFFFAOYSA-N 2-(aminomethyl)-1,3-thiazole-4-carbonitrile Chemical compound NCC1=NC(C#N)=CS1 TVPJJKGFBGKYGU-UHFFFAOYSA-N 0.000 description 1
- KIBISGAKFMLJOS-UHFFFAOYSA-N 2-[11-(2-methoxy-2-oxoethyl)-6-oxobenzo[b][1,4]benzodiazepin-5-yl]acetic acid Chemical compound OC(=O)CN1C(=O)C2=CC=CC=C2N(CC(=O)OC)C2=CC=CC=C21 KIBISGAKFMLJOS-UHFFFAOYSA-N 0.000 description 1
- RXDHVBBGYLYWSW-UHFFFAOYSA-N 2-[11-[2-[[4-(1h-benzimidazol-2-ylamino)phenyl]methylamino]-2-oxoethyl]-6-oxo-11h-benzo[c][1]benzazepin-5-yl]acetic acid Chemical compound C12=CC=CC=C2C(=O)N(CC(=O)O)C2=CC=CC=C2C1CC(=O)NCC(C=C1)=CC=C1NC1=NC2=CC=CC=C2N1 RXDHVBBGYLYWSW-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- JGJBNTXDCIPWJP-UHFFFAOYSA-N 2-[4-(1h-benzimidazol-2-yl)phenyl]ethanamine Chemical compound C1=CC(CCN)=CC=C1C1=NC2=CC=CC=C2N1 JGJBNTXDCIPWJP-UHFFFAOYSA-N 0.000 description 1
- OZDGVKBHOLHLEE-UHFFFAOYSA-N 2-[4-(aminomethyl)-1,3-thiazol-2-yl]guanidine Chemical compound NCC1=CSC(N=C(N)N)=N1 OZDGVKBHOLHLEE-UHFFFAOYSA-N 0.000 description 1
- HRQOLASXHFHGIK-UHFFFAOYSA-N 2-[5-[(1,3-dioxoisoindol-2-yl)methyl]-1,3-thiazol-2-yl]guanidine Chemical compound S1C(NC(=N)N)=NC=C1CN1C(=O)C2=CC=CC=C2C1=O HRQOLASXHFHGIK-UHFFFAOYSA-N 0.000 description 1
- LGMCLAGITHOGFT-UHFFFAOYSA-N 2-[5-[2-[[2-(benzylcarbamoylamino)-1,3-thiazol-4-yl]methylamino]-2-oxoethyl]-6-oxobenzo[b][1,4]benzodiazepin-11-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2N(CC(=O)O)C2=CC=CC=C2N1CC(=O)NCC(N=1)=CSC=1NC(=O)NCC1=CC=CC=C1 LGMCLAGITHOGFT-UHFFFAOYSA-N 0.000 description 1
- HLHGBUDVJAFBRN-UHFFFAOYSA-N 2-amino-1,3-oxazole-4-carboxylic acid Chemical compound NC1=NC(C(O)=O)=CO1 HLHGBUDVJAFBRN-UHFFFAOYSA-N 0.000 description 1
- REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 1
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
- 125000004710 2-methylpropylthio group Chemical group CC(CS*)C 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- PXJBCMWIAPDWAU-UHFFFAOYSA-N 2-piperidin-4-ylethanamine Chemical compound NCCC1CCNCC1 PXJBCMWIAPDWAU-UHFFFAOYSA-N 0.000 description 1
- BGFISPDIDBIVFH-UHFFFAOYSA-N 2-pyrrolidin-3-ylethanamine Chemical compound NCCC1CCNC1 BGFISPDIDBIVFH-UHFFFAOYSA-N 0.000 description 1
- RZBWGEXTRWUGBV-UHFFFAOYSA-N 3,6-dimethylbenzene-1,2-diamine Chemical group CC1=CC=C(C)C(N)=C1N RZBWGEXTRWUGBV-UHFFFAOYSA-N 0.000 description 1
- XQIGCIKMXNANJT-UHFFFAOYSA-N 3-amino-1,2,4-triazole-3-carboxylic acid Chemical compound OC(=O)C1(N)N=CN=N1 XQIGCIKMXNANJT-UHFFFAOYSA-N 0.000 description 1
- YNDAMDVOGKACTP-UHFFFAOYSA-N 3-aminopyrrolidin-2-one Chemical compound NC1CCNC1=O YNDAMDVOGKACTP-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- VJAXCBJUBWJIRY-UHFFFAOYSA-N 3-oxo-1,2-dihydroisoindole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2CNC(=O)C2=C1 VJAXCBJUBWJIRY-UHFFFAOYSA-N 0.000 description 1
- XSZYBMMYQCYIPC-UHFFFAOYSA-N 4,5-dimethyl-1,2-phenylenediamine Chemical group CC1=CC(N)=C(N)C=C1C XSZYBMMYQCYIPC-UHFFFAOYSA-N 0.000 description 1
- COBDBODFRUNTMX-UHFFFAOYSA-N 4-(1h-benzimidazol-2-yl)-n-methyl-1,3-thiazol-2-amine Chemical compound S1C(NC)=NC(C=2NC3=CC=CC=C3N=2)=C1 COBDBODFRUNTMX-UHFFFAOYSA-N 0.000 description 1
- VQFBXSRZSUJGOF-UHFFFAOYSA-N 4-(1h-benzimidazol-2-yl)aniline Chemical compound C1=CC(N)=CC=C1C1=NC2=CC=CC=C2N1 VQFBXSRZSUJGOF-UHFFFAOYSA-N 0.000 description 1
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
- JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 description 1
- LXFOQDLDXLCQAI-UHFFFAOYSA-N 4-(4-nitrophenyl)butyl methanesulfonate Chemical compound CS(=O)(=O)OCCCCC1=CC=C([N+]([O-])=O)C=C1 LXFOQDLDXLCQAI-UHFFFAOYSA-N 0.000 description 1
- BXIXXXYDDJVHDL-UHFFFAOYSA-N 4-Chloro-ortho-phenylenediamine Chemical compound NC1=CC=C(Cl)C=C1N BXIXXXYDDJVHDL-UHFFFAOYSA-N 0.000 description 1
- IGYOWYHQEDUXIC-UHFFFAOYSA-N 4-[(pyridin-2-ylamino)methyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1CNC1=CC=CC=N1 IGYOWYHQEDUXIC-UHFFFAOYSA-N 0.000 description 1
- APTHSBLGVMYQRL-UHFFFAOYSA-N 4-amino-1h-pyrrole-2-carboxylic acid Chemical compound NC1=CNC(C(O)=O)=C1 APTHSBLGVMYQRL-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- WZWIQYMTQZCSKI-UHFFFAOYSA-N 4-cyanobenzaldehyde Chemical compound O=CC1=CC=C(C#N)C=C1 WZWIQYMTQZCSKI-UHFFFAOYSA-N 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 description 1
- KVVFXAAMMFTLGN-UHFFFAOYSA-N 5,11-dihydrobenzo[b][1,4]benzodiazepin-6-one Chemical compound O=C1NC2=CC=CC=C2NC2=CC=CC=C12 KVVFXAAMMFTLGN-UHFFFAOYSA-N 0.000 description 1
- ZIFSWCUCJMIKQC-UHFFFAOYSA-N 5-(aminomethyl)pyridine-2-carbonitrile Chemical compound NCC1=CC=C(C#N)N=C1 ZIFSWCUCJMIKQC-UHFFFAOYSA-N 0.000 description 1
- IJJWOSAXNHWBPR-HUBLWGQQSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-(6-hydrazinyl-6-oxohexyl)pentanamide Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)NCCCCCC(=O)NN)SC[C@@H]21 IJJWOSAXNHWBPR-HUBLWGQQSA-N 0.000 description 1
- BRXPDBOCAWXPLY-UHFFFAOYSA-N 5-amino-1-methylpyrazole-3-carboxylic acid Chemical compound CN1N=C(C(O)=O)C=C1N BRXPDBOCAWXPLY-UHFFFAOYSA-N 0.000 description 1
- UYTYLLQCQDBCDW-UHFFFAOYSA-N 5-amino-2-methylpyrazole-3-carboxylic acid Chemical compound CN1N=C(N)C=C1C(O)=O UYTYLLQCQDBCDW-UHFFFAOYSA-N 0.000 description 1
- PPKYDYFPGZQNFM-UHFFFAOYSA-N 5-amino-2h-1,3,4-thiadiazole-5-carboxylic acid Chemical compound OC(=O)C1(N)SCN=N1 PPKYDYFPGZQNFM-UHFFFAOYSA-N 0.000 description 1
- USJALFVAJSYMSN-UHFFFAOYSA-N 5h-benzo[c][1]benzazepine-6,11-dione Chemical compound O=C1NC2=CC=CC=C2C(=O)C2=CC=CC=C12 USJALFVAJSYMSN-UHFFFAOYSA-N 0.000 description 1
- MSAXVCTWRJWHBK-UHFFFAOYSA-N 5h-thieno[3,2-c][1]benzazepine-4,10-dione Chemical compound O=C1NC2=CC=CC=C2C(=O)C2=C1C=CS2 MSAXVCTWRJWHBK-UHFFFAOYSA-N 0.000 description 1
- PLBGSKFEBBMGMW-UHFFFAOYSA-N 5h-thieno[3,4-c][1]benzazepine-4,10-dione Chemical compound O=C1NC2=CC=CC=C2C(=O)C2=CSC=C12 PLBGSKFEBBMGMW-UHFFFAOYSA-N 0.000 description 1
- HEOQXHNKRXRCTO-UHFFFAOYSA-N 6,7,8,9-tetrahydro-5h-benzo[7]annulene Chemical class C1CCCCC2=CC=CC=C21 HEOQXHNKRXRCTO-UHFFFAOYSA-N 0.000 description 1
- ZRORKGRZXOBDPQ-UHFFFAOYSA-N 6h-pyrido[3,2-c][1]benzazepine-5,11-dione Chemical compound O=C1NC2=CC=CC=C2C(=O)C2=NC=CC=C12 ZRORKGRZXOBDPQ-UHFFFAOYSA-N 0.000 description 1
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 1
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 125000006416 CBr Chemical group BrC* 0.000 description 1
- ZNUMVNVVDYSLHI-UHFFFAOYSA-N CC(=O)OC1C2=CC=CC=C2N(C(=O)C3=CSC=C13)CC(=O)NCC4=CC=C(C=C4)NC5=NC6=CC=CC=C6N5 Chemical compound CC(=O)OC1C2=CC=CC=C2N(C(=O)C3=CSC=C13)CC(=O)NCC4=CC=C(C=C4)NC5=NC6=CC=CC=C6N5 ZNUMVNVVDYSLHI-UHFFFAOYSA-N 0.000 description 1
- CAZLMBJMFZFSJL-UHFFFAOYSA-N CC(=O)[O-].C1=CC=C2C(=C1)C(C3=CC=CC=C3N(C2=O)CC(=O)NCC4=NC5=CC=CC=C5[NH2+]4)CC(=O)O Chemical compound CC(=O)[O-].C1=CC=C2C(=C1)C(C3=CC=CC=C3N(C2=O)CC(=O)NCC4=NC5=CC=CC=C5[NH2+]4)CC(=O)O CAZLMBJMFZFSJL-UHFFFAOYSA-N 0.000 description 1
- 125000006414 CCl Chemical group ClC* 0.000 description 1
- XOJGAMCMKXVTNC-UHFFFAOYSA-N CN.OC(C(F)(F)F)=O.OC(C(F)(F)F)=O Chemical compound CN.OC(C(F)(F)F)=O.OC(C(F)(F)F)=O XOJGAMCMKXVTNC-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010048623 Collagen Receptors Proteins 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- 101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 description 1
- 108700021041 Disintegrin Proteins 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 108010012088 Fibrinogen Receptors Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 241000545744 Hirudinea Species 0.000 description 1
- 101000803709 Homo sapiens Vitronectin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102100022337 Integrin alpha-V Human genes 0.000 description 1
- 102000000507 Integrin alpha2 Human genes 0.000 description 1
- 108010028750 Integrin-Binding Sialoprotein Proteins 0.000 description 1
- 102000016921 Integrin-Binding Sialoprotein Human genes 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- 102000007547 Laminin Human genes 0.000 description 1
- 108010085895 Laminin Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- SCIFESDRCALIIM-VIFPVBQESA-N N-methyl-L-phenylalanine Chemical compound C[NH2+][C@H](C([O-])=O)CC1=CC=CC=C1 SCIFESDRCALIIM-VIFPVBQESA-N 0.000 description 1
- QAADZYUXQLUXFX-UHFFFAOYSA-N N-phenylmethylthioformamide Natural products S=CNCC1=CC=CC=C1 QAADZYUXQLUXFX-UHFFFAOYSA-N 0.000 description 1
- 208000034827 Neointima Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- YQVCIKFPOFJSBX-UHFFFAOYSA-N OC(=O)C(F)(F)F.C1CC(CN)CCN1C(=O)OCC1=CC=CC=C1 Chemical compound OC(=O)C(F)(F)F.C1CC(CN)CCN1C(=O)OCC1=CC=CC=C1 YQVCIKFPOFJSBX-UHFFFAOYSA-N 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- 101150044441 PECAM1 gene Proteins 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 102000007000 Tenascin Human genes 0.000 description 1
- 108010008125 Tenascin Proteins 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 108010048673 Vitronectin Receptors Proteins 0.000 description 1
- 239000003875 Wang resin Substances 0.000 description 1
- NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 1
- VISWSYLWBQHUFT-UHFFFAOYSA-N [5-[2-[[3-(benzylcarbamoylamino)phenyl]methylamino]-2-oxoethyl]-6-oxo-11h-benzo[c][1]benzazepin-11-yl] acetate Chemical compound O=C1C2=CC=CC=C2C(OC(=O)C)C2=CC=CC=C2N1CC(=O)NCC(C=1)=CC=CC=1NC(=O)NCC1=CC=CC=C1 VISWSYLWBQHUFT-UHFFFAOYSA-N 0.000 description 1
- IGWHHYZQZFNNSR-UHFFFAOYSA-N [5-[2-[[4-(1h-benzimidazol-2-ylamino)phenyl]methylamino]-2-oxoethyl]-6-oxo-11h-benzo[c][1]benzazepin-11-yl] acetate Chemical compound O=C1C2=CC=CC=C2C(OC(=O)C)C2=CC=CC=C2N1CC(=O)NCC(C=C1)=CC=C1NC1=NC2=CC=CC=C2N1 IGWHHYZQZFNNSR-UHFFFAOYSA-N 0.000 description 1
- DUPQLZYXNDYWLC-UHFFFAOYSA-N [6-(4,5-dihydro-1h-imidazol-2-yl)pyridin-3-yl]methanamine Chemical compound N1=CC(CN)=CC=C1C1=NCCN1 DUPQLZYXNDYWLC-UHFFFAOYSA-N 0.000 description 1
- LKNZRNDBNAYOFU-UHFFFAOYSA-N [6-oxo-5-[3-oxo-3-[(1-pyridin-2-ylpiperidin-4-yl)methylamino]propyl]-11h-benzo[c][1]benzazepin-11-yl] acetate Chemical compound O=C1C2=CC=CC=C2C(OC(=O)C)C2=CC=CC=C2N1CCC(=O)NCC(CC1)CCN1C1=CC=CC=N1 LKNZRNDBNAYOFU-UHFFFAOYSA-N 0.000 description 1
- WEYATHLMPPBTGK-UHFFFAOYSA-N [8-(aminomethyl)-2-oxa-3-azaspiro[4.4]non-3-en-4-yl] acetate Chemical compound CC(=O)OC1=NOCC11CC(CN)CC1 WEYATHLMPPBTGK-UHFFFAOYSA-N 0.000 description 1
- HZWNZGNZJCVSKS-UHFFFAOYSA-N [8-(aminomethyl)-2-oxa-3-azaspiro[4.5]dec-3-en-4-yl] acetate Chemical compound CC(=O)OC1=NOCC11CCC(CN)CC1 HZWNZGNZJCVSKS-UHFFFAOYSA-N 0.000 description 1
- BHIRTUJCQXDFRD-UHFFFAOYSA-N [Si].[P].[S] Chemical compound [Si].[P].[S] BHIRTUJCQXDFRD-UHFFFAOYSA-N 0.000 description 1
- ZMQBBPRAZLACCW-UHFFFAOYSA-N acetic acid;dichloromethane Chemical compound ClCCl.CC(O)=O ZMQBBPRAZLACCW-UHFFFAOYSA-N 0.000 description 1
- 125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 208000021328 arterial occlusion Diseases 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 150000001538 azepines Chemical class 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 150000001602 bicycloalkyls Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- IPQKJUKUHMSERU-UHFFFAOYSA-N butane-1,4-diamine;2,2,2-trifluoroacetic acid Chemical compound NCCCCN.OC(=O)C(F)(F)F IPQKJUKUHMSERU-UHFFFAOYSA-N 0.000 description 1
- IQRJSOSZPBPTHX-UHFFFAOYSA-N butyl n-[(4-aminophenyl)methyl]carbamate Chemical compound CCCCOC(=O)NCC1=CC=C(N)C=C1 IQRJSOSZPBPTHX-UHFFFAOYSA-N 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbamic acid group Chemical group C(N)(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- ONCCWDRMOZMNSM-FBCQKBJTSA-N compound Z Chemical compound N1=C2C(=O)NC(N)=NC2=NC=C1C(=O)[C@H]1OP(O)(=O)OC[C@H]1O ONCCWDRMOZMNSM-FBCQKBJTSA-N 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 229920001577 copolymer Chemical class 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- OKGXJRGLYVRVNE-UHFFFAOYSA-N diaminomethylidenethiourea Chemical compound NC(N)=NC(N)=S OKGXJRGLYVRVNE-UHFFFAOYSA-N 0.000 description 1
- 150000007654 dibenzocycloheptanes Chemical class 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical compound CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- HCFPRFJJTHMING-UHFFFAOYSA-N ethane-1,2-diamine;hydron;chloride Chemical compound [Cl-].NCC[NH3+] HCFPRFJJTHMING-UHFFFAOYSA-N 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- IEMGWBMVQLVHEY-UHFFFAOYSA-N ethyl 2-(3-amino-6,7-dihydro-5h-cyclopenta[b]pyridin-7-yl)acetate Chemical compound NC1=CN=C2C(CC(=O)OCC)CCC2=C1 IEMGWBMVQLVHEY-UHFFFAOYSA-N 0.000 description 1
- VNZXERIGKZNEKB-UHFFFAOYSA-N ethyl 2-amino-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(N)S1 VNZXERIGKZNEKB-UHFFFAOYSA-N 0.000 description 1
- VICYTAYPKBLQFB-UHFFFAOYSA-N ethyl 3-bromo-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CBr VICYTAYPKBLQFB-UHFFFAOYSA-N 0.000 description 1
- LIKFZBWZGQWAMR-UHFFFAOYSA-N ethyl 4-(pyridin-2-ylamino)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1NC1=CC=CC=N1 LIKFZBWZGQWAMR-UHFFFAOYSA-N 0.000 description 1
- GQQQULCEHJQUJT-UHFFFAOYSA-N ethyl 4-aminopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(N)CC1 GQQQULCEHJQUJT-UHFFFAOYSA-N 0.000 description 1
- IZCSREAMZDZVFW-UHFFFAOYSA-N ethyl 5-amino-1,3-thiazole-2-carboxylate Chemical compound CCOC(=O)C1=NC=C(N)S1 IZCSREAMZDZVFW-UHFFFAOYSA-N 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- FATAVLOOLIRUNA-UHFFFAOYSA-N formylmethyl Chemical group [CH2]C=O FATAVLOOLIRUNA-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 108010064365 glycyl- arginyl-glycyl-aspartyl-seryl-prolyl-lysine Proteins 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- CALVPZNSFFEPJG-UHFFFAOYSA-N guanidine;dihydrochloride Chemical compound Cl.Cl.NC(N)=N CALVPZNSFFEPJG-UHFFFAOYSA-N 0.000 description 1
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- LEUJVEZIEALICS-UHFFFAOYSA-N hydrogen sulfate;1h-imidazol-2-ylazanium Chemical compound OS(O)(=O)=O.NC1=NC=CN1 LEUJVEZIEALICS-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 239000004179 indigotine Substances 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 150000002545 isoxazoles Chemical class 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 150000007527 lewis bases Chemical group 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- BHJKDKXKOQYKFD-UHFFFAOYSA-N methyl 2-[5-[2-[[2-(benzylcarbamoylamino)-1,3-thiazol-4-yl]methylamino]-2-oxoethyl]-6-oxobenzo[b][1,4]benzodiazepin-11-yl]acetate Chemical compound O=C1C2=CC=CC=C2N(CC(=O)OC)C2=CC=CC=C2N1CC(=O)NCC(N=1)=CSC=1NC(=O)NCC1=CC=CC=C1 BHJKDKXKOQYKFD-UHFFFAOYSA-N 0.000 description 1
- VBRGRTKDGOMYMJ-UHFFFAOYSA-N methyl 2-amino-2h-pyrimidine-1-carboxylate Chemical compound COC(=O)N1C=CC=NC1N VBRGRTKDGOMYMJ-UHFFFAOYSA-N 0.000 description 1
- SVWWNEYBEFASMP-UHFFFAOYSA-N methyl 2-aminopyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(N)=C1 SVWWNEYBEFASMP-UHFFFAOYSA-N 0.000 description 1
- CTSAXXHOGZNKJR-UHFFFAOYSA-N methyl 2-diethoxyphosphorylacetate Chemical compound CCOP(=O)(OCC)CC(=O)OC CTSAXXHOGZNKJR-UHFFFAOYSA-N 0.000 description 1
- XQNRXJWIFJQYPP-UHFFFAOYSA-N methyl 4-(aminomethyl)thiophene-2-carboxylate Chemical compound COC(=O)C1=CC(CN)=CS1 XQNRXJWIFJQYPP-UHFFFAOYSA-N 0.000 description 1
- YHOVYZINCVIRGK-UHFFFAOYSA-N methyl 4-aminopyridine-2-carboxylate Chemical compound COC(=O)C1=CC(N)=CC=N1 YHOVYZINCVIRGK-UHFFFAOYSA-N 0.000 description 1
- PYQRUDYLXHRTQU-UHFFFAOYSA-N methyl 4-aminopyrimidine-2-carboxylate Chemical compound COC(=O)C1=NC=CC(N)=N1 PYQRUDYLXHRTQU-UHFFFAOYSA-N 0.000 description 1
- MBGSRKHDEJNWED-UHFFFAOYSA-N methyl 5-aminopyridine-3-carboxylate Chemical compound COC(=O)C1=CN=CC(N)=C1 MBGSRKHDEJNWED-UHFFFAOYSA-N 0.000 description 1
- URSUGGQRGURMAM-UHFFFAOYSA-N methyl 6-aminopyrimidine-4-carboxylate Chemical compound COC(=O)C1=CC(N)=NC=N1 URSUGGQRGURMAM-UHFFFAOYSA-N 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- TYHXIJJQIJKFSO-UHFFFAOYSA-N n'-pyridin-2-ylethane-1,2-diamine Chemical compound NCCNC1=CC=CC=N1 TYHXIJJQIJKFSO-UHFFFAOYSA-N 0.000 description 1
- UJQMLHKSZKBMMO-UHFFFAOYSA-N n,n-diethylethanamine;pyridine Chemical compound C1=CC=NC=C1.CCN(CC)CC UJQMLHKSZKBMMO-UHFFFAOYSA-N 0.000 description 1
- DBNQIOANXZVWIP-UHFFFAOYSA-N n,n-dimethyl-1,1-bis[(2-methylpropan-2-yl)oxy]methanamine Chemical compound CC(C)(C)OC(N(C)C)OC(C)(C)C DBNQIOANXZVWIP-UHFFFAOYSA-N 0.000 description 1
- AUGYAZFAXVSDQN-UHFFFAOYSA-N n-(2-piperidin-4-ylethyl)pyridin-2-amine Chemical compound C=1C=CC=NC=1NCCC1CCNCC1 AUGYAZFAXVSDQN-UHFFFAOYSA-N 0.000 description 1
- SVHUSZJOBWKPRF-UHFFFAOYSA-N n-(2-pyrrolidin-3-ylethyl)pyridin-2-amine Chemical compound C=1C=CC=NC=1NCCC1CCNC1 SVHUSZJOBWKPRF-UHFFFAOYSA-N 0.000 description 1
- PZVOFVCTIUPSRP-UHFFFAOYSA-N n-(piperidin-4-ylmethyl)pyridin-2-amine Chemical compound C1CNCCC1CNC1=CC=CC=N1 PZVOFVCTIUPSRP-UHFFFAOYSA-N 0.000 description 1
- PNBLAGJAUXZQTL-UHFFFAOYSA-N n-(pyridin-2-ylcarbamothioyl)benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(=S)NC1=CC=CC=N1 PNBLAGJAUXZQTL-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 150000002916 oxazoles Chemical class 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000003331 prothrombotic effect Effects 0.000 description 1
- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 150000004892 pyridazines Chemical class 0.000 description 1
- SLUHLANJIVXTRQ-UHFFFAOYSA-N pyridin-2-ylthiourea Chemical compound NC(=S)NC1=CC=CC=N1 SLUHLANJIVXTRQ-UHFFFAOYSA-N 0.000 description 1
- ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical compound NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 229940107685 reopro Drugs 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- LHJZQQDQPDWNNI-UHFFFAOYSA-N tert-butyl 4-(phenylmethoxycarbonylaminomethyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CNC(=O)OCC1=CC=CC=C1 LHJZQQDQPDWNNI-UHFFFAOYSA-N 0.000 description 1
- QYJVBVKFXDHFPQ-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)-n-methylcarbamate Chemical compound NCCN(C)C(=O)OC(C)(C)C QYJVBVKFXDHFPQ-UHFFFAOYSA-N 0.000 description 1
- ZFQWJXFJJZUVPI-UHFFFAOYSA-N tert-butyl n-(4-aminobutyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCCN ZFQWJXFJJZUVPI-UHFFFAOYSA-N 0.000 description 1
- NGACMARYMMZIFV-UHFFFAOYSA-N tert-butyl n-(5-aminopentyl)carbamate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)NCCCCCN NGACMARYMMZIFV-UHFFFAOYSA-N 0.000 description 1
- UEKQQXCNRVBVDG-UHFFFAOYSA-N tert-butyl n-[(4-cyano-1,3-thiazol-2-yl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=NC(C#N)=CS1 UEKQQXCNRVBVDG-UHFFFAOYSA-N 0.000 description 1
- XAMAFLWCELXNAY-UHFFFAOYSA-N tert-butyl n-[(4-cyanophenyl)methyl]-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)CC1=CC=C(C#N)C=C1 XAMAFLWCELXNAY-UHFFFAOYSA-N 0.000 description 1
- FGXAGUHSZCNPBW-UHFFFAOYSA-N tert-butyl n-[4-[(2-aminophenyl)carbamothioylamino]butyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCCNC(=S)NC1=CC=CC=C1N FGXAGUHSZCNPBW-UHFFFAOYSA-N 0.000 description 1
- JXTCCKRUXCPBHU-UHFFFAOYSA-N tert-butyl n-[5-[(2-aminophenyl)carbamothioylamino]pentyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCCCNC(=S)NC1=CC=CC=C1N JXTCCKRUXCPBHU-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 150000003511 tertiary amides Chemical class 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000004867 thiadiazoles Chemical class 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 150000003918 triazines Chemical class 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 230000006444 vascular growth Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
- C07D223/20—Dibenz [b, e] azepines; Hydrogenated dibenz [b, e] azepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/38—[b, e]- or [b, f]-condensed with six-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Vascular Medicine (AREA)
- Communicable Diseases (AREA)
- Dermatology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pain & Pain Management (AREA)
- Virology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19936780A DE19936780A1 (de) | 1999-08-09 | 1999-08-09 | Neue Antagonisten von Integrinrezeptoren |
PCT/EP2000/007440 WO2001010847A2 (fr) | 1999-08-09 | 2000-08-01 | Nouveaux antagonistes des recepteurs integrines |
Publications (1)
Publication Number | Publication Date |
---|---|
SK2002002A3 true SK2002002A3 (en) | 2002-11-06 |
Family
ID=7917208
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK200-2002A SK2002002A3 (en) | 1999-08-09 | 2000-08-01 | Novel integrin receptor antagonists |
Country Status (20)
Country | Link |
---|---|
US (1) | US7105508B1 (fr) |
EP (1) | EP1202988A2 (fr) |
JP (1) | JP2003506441A (fr) |
KR (1) | KR20020019974A (fr) |
CN (1) | CN1374960A (fr) |
AU (1) | AU6990000A (fr) |
BG (1) | BG106395A (fr) |
BR (1) | BR0013265A (fr) |
CA (1) | CA2379977A1 (fr) |
CZ (1) | CZ2002439A3 (fr) |
DE (1) | DE19936780A1 (fr) |
HK (1) | HK1049001A1 (fr) |
HU (1) | HUP0204113A3 (fr) |
IL (1) | IL148043A0 (fr) |
MX (1) | MXPA02001379A (fr) |
NO (1) | NO20020644L (fr) |
PL (1) | PL354193A1 (fr) |
SK (1) | SK2002002A3 (fr) |
TR (1) | TR200200357T2 (fr) |
WO (1) | WO2001010847A2 (fr) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7601691B2 (en) | 1999-05-17 | 2009-10-13 | Conjuchem Biotechnologies Inc. | Anti-obesity agents |
US6887470B1 (en) * | 1999-09-10 | 2005-05-03 | Conjuchem, Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
DE10028575A1 (de) * | 2000-06-14 | 2002-03-14 | Basf Ag | Integrinliganden |
DE10039998A1 (de) * | 2000-08-11 | 2002-02-21 | Basf Ag | Neue substituierte Diareno-azepin-Derivate als Integrin Liganden |
WO2005052590A1 (fr) * | 2003-11-29 | 2005-06-09 | Proteogen, Inc. | Procede de criblage a rendement eleve pour antagoniste d'integrine et nouveau peptide crible obtenu par un tel procede |
PL2100904T3 (pl) * | 2004-04-23 | 2011-05-31 | Conjuchem Biotechnologies Inc | Stała faza do zastosowania w sposobie oczyszczania koniugatów albuminy |
WO2007053946A1 (fr) * | 2005-11-09 | 2007-05-18 | Conjuchem Biotechnologies Inc. | Procede de traitement du diabete et/ou de l'obesite en reduisant les effets secondaires nauseeux au moyen d'un peptide insulinotrope conjugue a de l'albumine |
WO2008011191A1 (fr) | 2006-07-21 | 2008-01-24 | Replidyne, Inc. | Urées hétérocycliques antibactériennes |
US8148380B2 (en) | 2007-07-23 | 2012-04-03 | Crestone, Inc. | Antibacterial amide and sulfonamide substituted heterocyclic urea compounds |
US8293919B2 (en) | 2007-07-23 | 2012-10-23 | Crestone, Inc. | Antibacterial sulfone and sulfoxide substituted heterocyclic urea compounds |
US8598158B2 (en) | 2009-12-14 | 2013-12-03 | Merck Sharp & Dohme Corp. | Fused tricyclic compounds for the treatment of inflammatory disorders |
WO2018181001A1 (fr) * | 2017-03-31 | 2018-10-04 | 三菱瓦斯化学株式会社 | Composé de phényle imidazoline ayant un groupe aminométhyle ou sel de celui-ci, ou composé de phényl tétrahydropyrimidine ayant un groupe aminométhyle ou sel de celui-ci, et procédé de production desdits composés ou sels correspondants |
EP3946618A1 (fr) | 2019-04-05 | 2022-02-09 | Storm Therapeutics Ltd | Composés inhibiteurs de mettl3 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0665664B2 (ja) | 1985-01-18 | 1994-08-24 | 大塚製薬株式会社 | モルフアントリジン誘導体 |
EP0910563B1 (fr) * | 1995-06-29 | 2003-05-02 | Smithkline Beecham Corporation | Antagonistes du recepteur de l'integrine |
CO4920232A1 (es) | 1997-01-08 | 2000-05-29 | Smithkline Beecham Corp | Acidos aceticos dibenzo [a,d] cicloheptano con actividad antagonista del receptor de vitronectin |
WO1999005107A1 (fr) | 1997-07-25 | 1999-02-04 | Smithkline Beecham Corporation | Antagonistes du recepteur de vitronectine |
CA2304117A1 (fr) | 1997-09-04 | 1999-03-11 | Dirk A. Heerding | Antagonistes des recepteurs d'integrines |
DZ2609A1 (fr) * | 1997-09-19 | 2003-03-01 | Smithkline Beecham Corp | Composés nouveaux antagonistes des récepteurs de vitronectine et compositions pharmaceutiques les contenant. |
EE200000360A (et) * | 1997-12-17 | 2001-12-17 | Merck & Co., Inc. | Integriini retseptori antagonistid, farmatseutiline kompositsioon ja selle valmistamismeetod |
HUP0101320A3 (en) | 1998-01-21 | 2002-11-28 | Kyowa Hakko Kogyo Kk | Benzo- and pyridobenzoxepine and -benzazepine derivatives and use thereof |
-
1999
- 1999-08-09 DE DE19936780A patent/DE19936780A1/de not_active Withdrawn
-
2000
- 2000-08-01 BR BR0013265-9A patent/BR0013265A/pt not_active IP Right Cessation
- 2000-08-01 SK SK200-2002A patent/SK2002002A3/sk unknown
- 2000-08-01 JP JP2001515313A patent/JP2003506441A/ja active Pending
- 2000-08-01 KR KR1020027001861A patent/KR20020019974A/ko not_active Ceased
- 2000-08-01 AU AU69900/00A patent/AU6990000A/en not_active Abandoned
- 2000-08-01 CA CA002379977A patent/CA2379977A1/fr not_active Abandoned
- 2000-08-01 TR TR2002/00357T patent/TR200200357T2/xx unknown
- 2000-08-01 CN CN00813099A patent/CN1374960A/zh active Pending
- 2000-08-01 PL PL00354193A patent/PL354193A1/xx not_active Application Discontinuation
- 2000-08-01 CZ CZ2002439A patent/CZ2002439A3/cs unknown
- 2000-08-01 HU HU0204113A patent/HUP0204113A3/hu unknown
- 2000-08-01 MX MXPA02001379A patent/MXPA02001379A/es active IP Right Grant
- 2000-08-01 WO PCT/EP2000/007440 patent/WO2001010847A2/fr not_active Application Discontinuation
- 2000-08-01 EP EP00958347A patent/EP1202988A2/fr not_active Withdrawn
- 2000-08-01 IL IL14804300A patent/IL148043A0/xx unknown
- 2000-08-01 US US10/049,266 patent/US7105508B1/en not_active Expired - Lifetime
-
2002
- 2002-02-06 BG BG106395A patent/BG106395A/bg unknown
- 2002-02-08 NO NO20020644A patent/NO20020644L/no not_active Application Discontinuation
-
2003
- 2003-02-18 HK HK03101187.8A patent/HK1049001A1/zh unknown
Also Published As
Publication number | Publication date |
---|---|
CN1374960A (zh) | 2002-10-16 |
JP2003506441A (ja) | 2003-02-18 |
EP1202988A2 (fr) | 2002-05-08 |
CA2379977A1 (fr) | 2001-02-15 |
BG106395A (bg) | 2002-12-29 |
IL148043A0 (en) | 2002-09-12 |
AU6990000A (en) | 2001-03-05 |
DE19936780A1 (de) | 2001-02-15 |
US7105508B1 (en) | 2006-09-12 |
NO20020644D0 (no) | 2002-02-08 |
HUP0204113A3 (en) | 2003-11-28 |
WO2001010847A3 (fr) | 2001-11-01 |
KR20020019974A (ko) | 2002-03-13 |
CZ2002439A3 (cs) | 2002-11-13 |
HUP0204113A2 (hu) | 2003-04-28 |
TR200200357T2 (tr) | 2002-09-23 |
HK1049001A1 (zh) | 2003-04-25 |
WO2001010847A2 (fr) | 2001-02-15 |
WO2001010847A8 (fr) | 2001-12-06 |
PL354193A1 (en) | 2003-12-29 |
NO20020644L (no) | 2002-03-18 |
MXPA02001379A (es) | 2002-07-30 |
BR0013265A (pt) | 2002-05-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20100048536A1 (en) | Novel Substituted Diaryl Azepine Derivatives as Integrin Ligands | |
AU5128699A (en) | Integrin receptor antagonists | |
SK2002002A3 (en) | Novel integrin receptor antagonists | |
AU2864800A (en) | Benzazepine derivatives as alpha-v integrin receptor antagonists | |
JP3936844B2 (ja) | インテグリンレセプターリガンド | |
US20040259864A1 (en) | Substituted pyrimidinone derivatives as ligands of integrin receptors | |
US20080221082A1 (en) | Ligands of Integrin Receptors | |
MXPA01010834A (es) | Antagonistas de los receptores para integrina. | |
US20030171368A1 (en) | Pyrimidinonesulfamoylureas` | |
JP2004506637A (ja) | インテグリンリガンドとしての新規の置換されたジアリールアゼピン誘導体 | |
DE19948269A1 (de) | Neue Integrinrezeptorantagonisten | |
DE19962998A1 (de) | Integrinrezeptorliganden | |
DE19919218A1 (de) | Neue Integrinrezeptorantagonisten |