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WO2001000583A1 - Derives d'ucf 116 en tant qu'agents antitumoraux - Google Patents

Derives d'ucf 116 en tant qu'agents antitumoraux Download PDF

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Publication number
WO2001000583A1
WO2001000583A1 PCT/US2000/017625 US0017625W WO0100583A1 WO 2001000583 A1 WO2001000583 A1 WO 2001000583A1 US 0017625 W US0017625 W US 0017625W WO 0100583 A1 WO0100583 A1 WO 0100583A1
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WO
WIPO (PCT)
Prior art keywords
substituted
unsubstituted
heterocyclic group
isomer
solvate
Prior art date
Application number
PCT/US2000/017625
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English (en)
Inventor
Mitsunobu Hara
Shiro Akinaga
Yutaka Kanda
Timothy S. Powers
David A. Johnson
Original Assignee
Kyowa Hakko Kogyo Co., Ltd.
Eli Lilly & Co.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kyowa Hakko Kogyo Co., Ltd., Eli Lilly & Co. filed Critical Kyowa Hakko Kogyo Co., Ltd.
Priority to AU57695/00A priority Critical patent/AU5769500A/en
Publication of WO2001000583A1 publication Critical patent/WO2001000583A1/fr

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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
    • C07D401/12—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D225/00—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
    • C07D225/04—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D225/06—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • 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
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom 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
    • C07D409/02—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
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen 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
    • 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
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

Definitions

  • the present invention relates to novel UCFl16 derivatives or salts thereof which have antitumor and antibacterial activities and are useful as antitumor agents. Also, the present invention relates to a pharmaceutical composition which comprises the UCF116 derivative or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier .
  • Patent 4,587,23-7 ansatrienin A2 and ansatrienin A3 [Journal of Antibiotics , 36:187 (1983)], ansatrienin A4 [Journal of Natural Products, 50:108 (1987)] and hexadehydromycotrienin II [The Journal of Biological Chemistry, 270:25949 (1995) are known. It has been reported that these compounds have antibacterial activities and antitumor activities.
  • the present invention relates to UCF116 derivatives represented by formula (I) :
  • R la represents methyl , ethyl , propyl , isopropyl
  • R lc represents substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted heterocyclic group , or substituted or unsubstituted lower alkenyl) , with the proviso that, when Q is
  • R is not benzoyl , salts thereof, isomers thereof, hydrates thereof, or solvates thereof .
  • the present invention relates to a pharmaceutical composition, which comprises the above- described derivative, a pharmaceutically acceptable salt thereof, an isomer thereof, a hydrate thereof or a solvate thereof , and a pharmaceutically acceptable carrier .
  • an antitumor agent or antibacterial agent which comprises as an active ingredient the above-described derivative, a pharmaceutically acceptable salt thereof, an isomer thereof, a hydrate thereof or a solvate thereof.
  • examples of the lower alkyl include straight- or branched- chain alkyls having 1 to 10 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert- butyl, pentyl , isopentyl, hexyl , heptyl , octyl , nonyl , and decyl .
  • alkyl having 6 to 10 carbon atoms examples include those having 6 to 10 carbon atoms among the above- described lower alkyls.
  • alicyclic alkyl include those having 3 to 10 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl , cyclohexyl , cycloheptyl , cyclooctyl , and adamantyl .
  • Examples of the alicyclic alkyl having 3 to 5 carbon atoms include those having 3 to 5 carbon atoms among the above-described alicyclic alkyls .
  • a lower alkyl moiety contained in the lower alkoxycarbonyl has the same meaning as the above-described lower alkyl .
  • lower alkenyl examples include straight- or branched-chain or cyclic alkenyls having 2 to 8 carbon atoms , such as vinyl, allyl , crotyl, 1-propenyl, prenyl, isopropenyl, 2-methyl-2-butenyl, pentenyl , hexenyl, heptenyl , octenyl , cyclobutenyl , cyclopentenyl , and cyclohexenyl .
  • straight- or branched-chain or cyclic alkenyls having 2 to 8 carbon atoms such as vinyl, allyl , crotyl, 1-propenyl, prenyl, isopropenyl, 2-methyl-2-butenyl, pentenyl , hexenyl, heptenyl , octenyl , cyclobutenyl , cyclopentenyl , and cyclohex
  • the aryl is a mono- to tricyclic carbon ring composed of three- to seven-me bered rings in which at least one ring is an aromatic ring. Examples include phenyl, naphthyl , anthracenyl , tetrahydronaphthyl , indanyl , and phenanthrenyl .
  • aralkyl examples include those having 7 to 15 carbon atoms , such as benzyl , phenetyl , benzhydryl , naphthylmethyl , and fluorenylmethyl .
  • the heterocyclic group means a mono- to tricyclic ring composed of three- to eight-membered rings having 1 to 7 carbon atoms and contains at least one of nitrogen, oxygen and sulf r atoms .
  • heterocyclic groups such as azepinyl, benzi idazolyl , benzofurazanyl , benzopyranyl , benzothiopyranyl , benzof ryl, benzothiazolyl , benzothiadiazolyl , benzothienyl , benzoxazolyl , chromanyl , cinnolinyl, dihydrobenzofuryl , dihydrobenzothienyl , dihydrobenzothiopyranyl, furyl, imidazolidinyl , imidazolyl, imidazothiazolyl, indolinyl, indolyl , isochromanyl , isoindolyl, isoxazolyl, isoquinolyl, isothiazolyl , isothiazolidinyl , morpholinyl , naphthyridinyl , oxadiazolyl , oxazolyl ,
  • a substituent on the lower alkyl, alicyclic alkyl, alicyclic alkyl having 3 to 5 carbon atoms , lower alkenyl , lower alkoxycarbonyl , aryl , aralkyl , aralkyloxy or heterocyclic group is 1 to 3 substituents which are the same or different, such as hydroxy, halogen, nitro, amino, carboxy , cyano , lower alkyl , alicyclic alkyl , lower alkenyl , lower alkoxy, lower alkoxycarbonyl, lower alkanoyl, lower alkylthio, aryl, aryloxy, aryloxy (lower alkyl), lower alkylamino, di (lower alkyl) amino, lower alkanoylamino , aralkyl, aralkyloxy, arylamino, arylsulfonyl , and a heterocyclic group.
  • the halogen means a fluorine, chlorine, bromine or iodine atom
  • the lower alkyl, alicyclic alkyl, lower alkenyl, lower alkoxycarbonyl , aryl , aralkyl , aralkyloxy and heterocyclic group have the same meanings as defined above .
  • the lower alkyl moiety contained in the lower alkoxy, lower alkanoyl, lower alkylthio, lower alkylamino, di (lower alkyl) amino, lower alkanoylamino or aryloxy (lower alkyl) has the same meaning as the above-described lower alkyl .
  • the aryl moiety in the aryloxy, aryloxy (lower alkyl), arylamino and arylsulfonyl has the same meaning as the above-described aryl.
  • the substituent may be further substituted with a similar substituent.
  • the alkyl and aryl moieties of the above-described substituent may be substituted with 1 to 3 halogen atoms and the heterocyclic group may be substituted with 1 to 3 substituents such as lower alkyl and trifluoromethyl .
  • Compound (I) may form a salt, and examples of the salt and pharmaceutically acceptable salt of Compound (I) include an acid addition salt, a metal salt, an ammonium salt, an organic a ine addition salt and an amino acid addition salt.
  • the acid addition salt include an inorganic acid addition salt (e.g., hydrochloride , hydrobromide, sulfate, phosphate, nitrate) and an organic acid addition salt (e.g., formate, acetate, propionate, benzoate, maleate, fumarate , succinate, tartrate, citrate, oxalate, methanesulfonate , p-toluenesulfonate , aspartate, glutamate) .
  • an inorganic acid addition salt e.g., hydrochloride , hydrobromide, sulfate, phosphate, nitrate
  • an organic acid addition salt e.g., formate, acetate, propionate,
  • Examples of the metal salt include an alkali metal salt (e.g., lithium salt, sodium salt, potassium salt) and an alkaline earth metal salt (e.g., magnesium salt, calcium salt) , an aluminum salt, and a zinc salt.
  • Examples of the ammonium salt include ammonium and tetramethylammonium .
  • Examples of the organic amine addition salt include an addition salt of morpholine or piperidine .
  • Examples of the amino acid addition salt include an addition salt of glycine, phenylalanine , glutamic acid, or lysine.
  • Compound (I) may exist as a various isomer, such as a position isomer, a stereoisomer, an optical isomer, and a tautomer, and all possible isomers and their mixtures of every ratio are also included in the present invention.
  • Compound (I) and pharmaceutically acceptable salts thereof may exist in the form of an adduct with water or various solvents , and such adducts are also included in the present invention .
  • R la has the same meaning as defined above, and W represents an insoluble resin.
  • the insoluble resin represented by W means an insoluble resin generally used as a solid phase carrier in the field of combinatorial chemistry, peptide solid phase synthesis and the like, and a cross-linked polystyrene resin is used preferably.
  • the basic solid phase carrier for use in the present invention can be obtained as a commercial item or synthesized in accordance with known methods .
  • Compound lb in which R is R lb NHCO or R lb NHCS can be synthesized by allowing Compound 2 to react with various types of isocyanate
  • R c has the same meaning as defined above, and W represents an insoluble resin as defined above .
  • Compound Ic in which R is R lc S0 2 can be synthesized by allowing Compound 2 to react with various types of sulfonyl chloride (R lc S0 2 Cl) in an inert solvent, such as dichloromethane, in the presence of a basic resin, such as (piperidinomethy1) polystyrene. After completion of the reaction, a basic resin, such as (piperidinomethy1) polystyrene. After completion of the reaction, a basic resin, such as
  • respective compounds of interest can also be obtained using an organic base, such as pyridine, triethy1amine , or DMAP, instead of a basic resin, such as (piperidinomethyl) polystyrene or
  • Compound le can be synthesized by treating Compound Id with one equivalent to a large excess of a reducing agent, such as Na 2 S 2 0 ⁇ , in a solvent, such as methanol .
  • a reducing agent such as Na 2 S 2 0 ⁇
  • each of the reagents or insoluble resins used is not limited to the equivalent amount described in each reaction scheme, and they can be used in an amount of 1 to 10 equivalent based on the material compound. Also, in the above steps 1 to 5 , each reaction is carried out at a temperature of -80 to 60°C.
  • Isolation and purification of respective products formed in the above-described production methods can be carried out by employing optional combinations of techniques generally used in the field of organic synthesis , such as filtration, extraction, washing, drying, concentration, crystallization, and various chromatographic means.
  • Compound (I) or a pharmaceutically acceptable salt thereof is administered orally or parenterally as it is or as various pharmaceutical compositions .
  • the dosage form of the pharmaceutical compositions includes tablets, pills, powders, granules, capsules, suppositories, injections, and drops.
  • the composition may contain various excipients, lubricants, binders, disintegrators, suspending agents, isotonizing agents , emulsifiers , and absorbe acients .
  • Examples of the carrier used in the pharmaceutical compositions include water, distilled water for injection, physiological saline, glucose, fructose, sucrose, mannitol, lactose, starch, corn starch, cellulose, methyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, alginic acid, talc, sodium citrate, calcium carbonate, calcium hydrogen phosphate, magnesium stearate, urea, silicone resin, sorbitan fatty acid ester, and glycerine fatty acid ester. They are appropriately selected according to the kind of the preparation .
  • the dosage and administration schedule vary depending on the effect of treatment, the administration route, the period of treatment, the age, the body weight, and the like.
  • the compound is usually administered at a dose level of 0.01 mg to 200 mg/kg once or a few times per day for an adult orally or parenterally (for example, injection, drop, intrarectal administration by suppositories, application to skin) . Since the dosage depends on various factors as stated above, lower doses may be sufficient, or higher doses may be required.
  • the solid compositions for oral administration in the present invention include tablets, pills, capsules, powders, and granules .
  • the solid compositions are prepared by mixing at least one active ingredient with at least one inert diluent, such as lactose, mannitol, glucose, hydroxypropyl cellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone , metasilicate, and magnesium aluminate.
  • the solid compositions can contain customarily employed additives other than the inert diluent, such as lubricants (e.g., magnesium stearate), disintegrators (e.g., cellulose calcium glycolate) , stabilizers (e.g., human serum albumin, lactose) , and adjuvants for solubilization and dissolution (e.g., arginine, glutamic acid, aspartic acid).
  • lubricants e.g., magnesium stearate
  • disintegrators e.g., cellulose calcium glycolate
  • stabilizers e.g., human serum albumin, lactose
  • adjuvants for solubilization and dissolution e.g., arginine, glutamic acid, aspartic acid.
  • the tablets or pills can be coated with a film of a gastric or enteric substance (e.g., sucrose, gelatin, hydroxypropyl cellulose, hydroxypropylmethyl cellulose phthalate) .
  • a gastric or enteric substance e.g., sucrose, gelatin, hydroxypropyl cellulose, hydroxypropylmethyl cellulose phthalate
  • the capsules include hard capsules and soft capsules .
  • liquid compositions for oral administration include solutions, emulsions, suspensions, syrups, and elixirs .
  • the liquid compositions for oral administration can contain generally used inert diluents (e.g., purified water) .
  • the liquid compositions can contain adjuvants, such as wetting agents, adjuvants for solubilization and dissolution, suspending agents, sweeteners, flavors, aromatics, and antiseptics in addition to the inert diluents.
  • adjuvants such as wetting agents, adjuvants for solubilization and dissolution, suspending agents, sweeteners, flavors, aromatics, and antiseptics in addition to the inert diluents.
  • Other compositions for oral administration include sprays containing at least one active ingredient, which are prepared in a conventional manner . Sprays can contain stabilizers (e.g., sodium sulfite) and buffers for making the composition isotonic (e.g., sodium chloride, sodium citrate, citric acid) in addition to the inert diluents .
  • the injectable preparations for parenteral administration include sterile aqueous or nonaqueous solutions, suspension or emulsions.
  • the injectable preparations are prepared by mixing at least one active ingredient with at least one inert aqueous diluent (e.g., distilled water for injections, physiological saline) or inert nonaqueous diluent (e.g., propylene glycol, polyethylene glycol, plant oil such as olive oil, alcohol such as ethanol, Polysorbate 80 (registered trade name)) .
  • inert aqueous diluent e.g., distilled water for injections, physiological saline
  • inert nonaqueous diluent e.g., propylene glycol, polyethylene glycol, plant oil such as olive oil, alcohol such as ethanol, Polysorbate 80 (registered trade name)
  • they can further contain antiseptics, wetting agents, emulsifiers, dispersants, stabilizers (e.g., human serum albumin, lactose) , and adjuvants for solubilization and dissolution.
  • the resulting liquid compositions are usually sterilized by filtration, incorporation of bactericides or irradiation.
  • the sterilized composition may be solidified by, for example, freeze-drying, to obtain a solid composition, which is dissolved in aseptic water or aseptic diluent for injection on use.
  • Mycotrienol I (300 mg, 0.68 mmol) was taken up in 40 mL of dry CH 2 C1 2 under argon, and DMAP (414 mg, 3.40 mmol) was added thereto and stirred until completely dissolved. The reaction mixture was then cooled to -78 °C upon which (FMOC-D- Ala) 2 0 (362 mg, 0.60 mmol) was added neat. After stirring the mixture at -78°C for 8 hours, the reaction mixture was quenched with 10 g of silica gel and gradually warmed to room temperature over a 20 minute period.
  • Compound 2 (2.5 mg, 0.0048 mmol) was dissolved in 0.5 mL of dry CH 2 C1 2 and added to a single well containing (piperidinomethyl) polystyrene (3.0 mg, 0.0072 mmol, Fluka) in an unmodified 96-deep well plate (Beckman, cat. #267006, 1 mL/well) followed by an appropriate isothiocyanate or isocyanate (0.0058 mmol) in 0.4 mL of dry CH 2 C1 2 . The wells were immediately capped (Marsh Biochemical Products , cat .
  • Compound 2 (2.5 mg, 0.0048 mmol) was dissolved in 0.5 mL of dry CH 2 C1 2 with DMAP (6.0 mg, 0.48 mmol) and added to a single well containing (piperidinomethyl) polystyrene (3.0 mg, 0.0072 mml , Fluka) in an unmodified 96-deep well plate (Beckman, cat. #267006, 1 mL/well) followed by an appropriate sulfonylchloride (0.0058 mmol) in 0.4 mL of dry CH 2 C1 2 . The wells were immediately capped (Marsh Biochemical Products, cat.
  • Example 7 One of the plates containing crude Compounds 3-52 described in Example 3 was concentrated down to a thin film upon which Na 2 S 2 0 4 (ca. 5 mg/well) was added to each well followed by 0.9 mL of methanol . The wells were strip-capped and vortexed for 1 hour upon which the solution in each well turned colorless. The strip caps were removed and the contents of each well were passed through a glass pipette which contained a small pad of silica gel to filter excess Na 2 S 2 0 4 . The filtrate was concentrated to give white powdered thin films . This material was then analyzed by TLC and MS . Average yields were assumed to be 2 mg by random sampling and average purities were assumed to be more than 90% by TLC analysis. Thus, Compounds 123-170 were obtained. Example 7
  • Mycotrienin II (1.00 g, 1.56 mmol) was reduced with NaBH 4 as described by the literature method to afford 1.04 g of a crude material .
  • Test Example 1 pharmacological activities of Compound (I) are described with re erence to test examples .
  • KNRK cells adjusted to a density of lxlO 5 cells/ml were dispensed in 1 ml/well portions into a 24 well plate
  • DMEM Dulbecco' s modified Eagle' s medium
  • FCS 10% fetal calf serum
  • the thus recovered cells were washed with 0.5 ml of physiological saline and separated using 1 ml of a solution containing 0.125% trypsin and 0.01% EDTA, and a 0.5 ml portion of the resulting cell suspension was diluted with 10 ml of Cell Pack
  • Human colonic cancer HCT 116 was abdominal- subcutaneously transplanted into nude mice (female, CD-I nu/nu mice) and then, by arbitrarily dividing the mice into groups of 5 animals per group on the 7th day after the transplantation, a test compound dissolved in emulphor/PBS was intraperitoneally administered into each mouse once a day for 10 days to measure the tumor weight on the 14th day after commencement of the drug administration.
  • Antitumor activity of the test compound was expressed by the ratio (T/C) of the tumor volume (T) of the test drug-administered group to the tumor volume (C) of the drug-non-administered group on the 14th day after the administration. The results are shown in Table 5.

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Dérivés d'UCF116 représentés par la formule (I) (I) dans laquelle Q représente ou et R représente hydrogène, C(=O)R1a, C(=X)NHR1b ou SO¿2R?1c ou leurs sels possédant des activités antitumorales et antibactériennes, ainsi qu'une utilité en tant qu'agents antitumoraux.
PCT/US2000/017625 1999-06-28 2000-06-27 Derives d'ucf 116 en tant qu'agents antitumoraux WO2001000583A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU57695/00A AU5769500A (en) 1999-06-28 2000-06-27 Ucf116 derivatives as antitumor agents

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14083899P 1999-06-28 1999-06-28
US60/140,838 1999-06-28

Publications (1)

Publication Number Publication Date
WO2001000583A1 true WO2001000583A1 (fr) 2001-01-04

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6680187B2 (en) 2000-09-13 2004-01-20 Degussa Ag Nucleotide sequences coding for the PTSI protein

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4587237A (en) * 1985-09-06 1986-05-06 Nisshin Flour Milling Co., Ltd. Mycotrienin-related compounds
EP0739883A1 (fr) * 1994-11-15 1996-10-30 Kyowa Hakko Kogyo Co., Ltd. Composes ucf116

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4587237A (en) * 1985-09-06 1986-05-06 Nisshin Flour Milling Co., Ltd. Mycotrienin-related compounds
EP0739883A1 (fr) * 1994-11-15 1996-10-30 Kyowa Hakko Kogyo Co., Ltd. Composes ucf116

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6680187B2 (en) 2000-09-13 2004-01-20 Degussa Ag Nucleotide sequences coding for the PTSI protein

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