Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/16—Amides, e.g. hydroxamic acids
  • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
  • A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
  • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
  • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
  • A61K31/4406—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents

Definitions

• R5 is a hydrogen atom or an optionally substituted alkyl group having 1 to 4 carbons
• n is an integer of 0 to 4, provided that when X is a bond, n is not zero;
• RI and R2 are independently a hydrogen atom, a halogen atom, a hydroxyl group, an amino group, an alkyl group having 1 to 4 carbons, an alkoxy group having 1 to 4 carbons, an aminoalkyl group having 1 to 4 carbons, an alkylamino group having 1 to 4 carbons, an acyl group having 1 to 4 carbons, an acylamino group having 1 to 4 carbons, an alkylthio group having 1 to 4 carbons, a perfluoroalkyl group having 1 to 4 carbons, a perfluoroalkyloxy group having 1 to 4 carbons, a carboxyl group or an alkoxycarbonyl group having 1 to 4 carbons;
• R3 is a hydroxyl group or amino group or a pharmaceutically acceptable salt thereof as HDAC inhibiting substance, and
• the benzamide derivative is represented by the following formula (5) or pharmaceutically acceptable salt thereof:
• said ingredient (b) which is another anti-cancer active substance is preferably etoposide, more preferably the combination or composition which is for treatment of ovarian cancer.
• said ingredient (b) which is another anti-cancer active substance is preferably 5-fluorouracil, more preferably the combination or composition which is for treatment of breast cancer or colon cancer.
• said ingredient (b) which is another anti-cancer active substance is preferably gemcitabine, more preferably the combination or composition which is for treatment of non-small cell lung cancer, colon cancer or ovarian cancer.
• said ingredient (b) which is another anti-cancer active substance is preferably paclitaxel, more preferably the combination or composition which is for treatment of breast cancer, prostate cancer or ovarian cancer.
• said ingredient (b) which is another anti-cancer active substance is preferably docetaxel.
• said ingredient (a) which is a histone deacetylase inhibiting substance is more preferable.
• said ingredient (b) which is another anti-cancer active substance is preferably carboplatin.
• carboplatin As the administration sequence thereof, it is preferable to administer carboplatin, and then said ingredient (a) which is a histone deacetylase inhibiting substance.
• the pharmaceutical combination for treatment of non-small cell lung cancer, ovarian cancer, pancreatic cancer or prostate cancer is more preferable.
• said ingredient (b) which is another anti-cancer active substance is preferably oxaliplatin.
• said administration sequence thereof it is preferable to administer oxaliplatin, and then said ingredient (a) which is a histone deacetylase inhibiting substance.
• the pharmaceutical combination for treatment of colon cancer or ovarian cancer is more preferable.
• said ingredient (b) which is another anti-cancer active substance is preferably doxorubicin.
• said ingredient (a) which is a histone deacetylase inhibiting substance The pharmaceutical combination for treatment of ovarian cancer is more preferable.
• said ingredient (b) which is another anti-cancer active substance is preferably vinblastin.
• the pharmaceutical combination for treatment of non-small cell lung cancer is more preferable.
• the present invention relates to a pharmaceutical composition or combination comprising a benzamide derivative represented by formula (1) which is a histone deacetylase inhibiting substance and another anticancer active substance.
• a benzamide derivative represented by formula (1) which is a histone deacetylase inhibiting substance and another anticancer active substance.
• “1 to 4 carbons” means a carbon number per a single substituent; for example, for dialkyl substitution it means 2 to 8 carbons.
• a heterocycle in the compound represented by formula (1) is a monocyclic heterocycle having 5 or 6 members containing 1 to 4 nitrogen, oxygen or sulfur atoms or a bicyclic-fused heterocycle.
• the monocyclic heterocycle includes pyridine, pyrazine, pyrimidine, pyridazine, thiophene, furan, pyrrole, pyrazole, isoxazole, isothiazole, i idazole, oxazole, thiazole, piperidine, piperazine, pyrrolidine, quinuclidine, tetrahydrofuran, morpholine, thiomorpholine and the like.
• the bicyclic fused heterocycle includes quinoline; isoquinoline; naphthyridine; fused pyridines such as furopyridine, thienopyridine, pyrrolopyridine, oxazolopyridine, imidazolopyridine and thiazolopyridine; benzofuran; benzothiophene; benzimidazole and the like.
• a halogen may be fluorine, chlorine, bromine or iodine.
• An alkyl having 1 to 4 carbons includes methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl.
• An acyl having 1 to 4 carbons includes acetyl, propanoyl, butanoyl and like.
• An acylamino having 1 to 4 carbons includes acetylamino, propanoylamino, butanoylamino and the like.
• An alkylthio having 1 to 4 carbons includes methylthio, ethylthio, propylthio and the like.
• a perfluoroalkyl having 1 to 4 carbons includes trifluoromethyl, pentafluoroethyl and the like.
• a perfluoroalkyloxy having 1 to 4 carbons includes trifluoromethoxy, pentafluoroethoxy and the like.
• An alkoxycarbonyl having 1 to 4 carbons includes methoxycarbonyl and ethoxycarbonyl .
• An optionally substituted alkyl having 1 to 4 carbons includes methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl and these having 1 to 4 substituents selected from the group consisting of a halogen, hydroxyl, amino, nitro, cyano, phenyl and a heterocycle.
• the ingredient (a) which is a histone deacetylase inhibiting substance of this invention may be produced in accordance with the process of Japanese unexamined patent publication (Kokai) No. 10-152462. And, the ingredient (b) which is another anti-cancer active substance is commercially available or can be produced by known methods.
• Suppository may be formed using a variety of well-known carriers; for example, semi-synthetic glyceride, cocoa butter, higher alcohols, higher alcohol esters and polyethylene glycol.
• the pharmaceutical formulation may contain coloring agents, preservatives, perfumes, flavors, sweeteners and/or other drugs.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Pharmacology & Pharmacy (AREA)
• Chemical & Material Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Epidemiology (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Pyridine Compounds (AREA)

Priority Applications (13)

Applications Claiming Priority (2)

Publications (1)

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Country Status (27)

Cited By (33)

Families Citing this family (12)

Citations (6)

Family Cites Families (5)

• 2004
  • 2004-05-25 PE PE2004000533A patent/PE20050206A1/es not_active Application Discontinuation
  • 2004-05-26 CA CA002634709A patent/CA2634709A1/en not_active Abandoned
  • 2004-05-26 CN CNA2004800146332A patent/CN1794991A/zh active Pending
  • 2004-05-26 WO PCT/JP2004/007562 patent/WO2004103369A1/en not_active Ceased
  • 2004-05-26 JP JP2006519178A patent/JP2006526031A/ja active Pending
  • 2004-05-26 US US10/558,208 patent/US20070098816A1/en not_active Abandoned
  • 2004-05-26 BR BRPI0410959-7A patent/BRPI0410959A/pt not_active IP Right Cessation
  • 2004-05-26 EP EP04734923A patent/EP1626719A1/en not_active Withdrawn
  • 2004-05-26 RU RU2005140570/15A patent/RU2322971C2/ru active IP Right Revival
  • 2004-05-26 ME MEP-323/08A patent/MEP32308A/xx unknown
  • 2004-05-26 UA UAA200512454A patent/UA81499C2/xx unknown
  • 2004-05-26 UY UY28330A patent/UY28330A1/es not_active Application Discontinuation
  • 2004-05-26 NZ NZ543591A patent/NZ543591A/en unknown
  • 2004-05-26 CL CL200401278A patent/CL2004001278A1/es unknown
  • 2004-05-26 RS YUP-2005/0884A patent/RS20050884A/sr unknown
  • 2004-05-26 CN CNA2008101007303A patent/CN101322707A/zh active Pending
  • 2004-05-26 CA CA002527191A patent/CA2527191A1/en not_active Abandoned
  • 2004-05-26 AR ARP040101807A patent/AR045318A1/es not_active Application Discontinuation
  • 2004-05-26 MX MXPA05012345A patent/MXPA05012345A/es active IP Right Grant
  • 2004-05-26 CA CA002634765A patent/CA2634765A1/en not_active Abandoned
  • 2004-05-26 AU AU2004241873A patent/AU2004241873C1/en not_active Ceased
  • 2004-05-26 KR KR1020057022615A patent/KR100938712B1/ko not_active Expired - Fee Related
  • 2004-05-26 CA CA002634766A patent/CA2634766A1/en not_active Abandoned
  • 2004-05-26 TW TW093114934A patent/TW200505424A/zh unknown
• 2005
  • 2005-11-14 IL IL171941A patent/IL171941A0/en unknown
  • 2005-11-16 NO NO20055417A patent/NO20055417L/no not_active Application Discontinuation
  • 2005-11-24 ZA ZA200509515A patent/ZA200509515B/en unknown
  • 2005-11-25 CU CU20050237A patent/CU23490B7/es not_active IP Right Cessation
  • 2005-12-22 CO CO05129159A patent/CO5660262A2/es unknown
  • 2005-12-26 EC EC2005006253A patent/ECSP056253A/es unknown
• 2006
  • 2006-01-02 CR CR8163A patent/CR8163A/es not_active Application Discontinuation

Patent Citations (8)

Non-Patent Citations (2)

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