CN100448844C - 组蛋白脱乙酰酶抑制剂 - Google Patents

组蛋白脱乙酰酶抑制剂 Download PDF

Info

Publication number
CN100448844C
CN100448844C CNB2003801016717A CN200380101671A CN100448844C CN 100448844 C CN100448844 C CN 100448844C CN B2003801016717 A CNB2003801016717 A CN B2003801016717A CN 200380101671 A CN200380101671 A CN 200380101671A CN 100448844 C CN100448844 C CN 100448844C
Authority
CN
China
Prior art keywords
alkyl
group
aryl
compound
heteroaryl
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Fee Related
Application number
CNB2003801016717A
Other languages
English (en)
Chinese (zh)
Other versions
CN1705635A (zh
Inventor
S·雷派尔
F·加德特
I·帕坎
A·韦斯博格
D·德洛姆
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Methylgene Inc
Original Assignee
Methylgene Inc
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 Methylgene Inc filed Critical Methylgene Inc
Publication of CN1705635A publication Critical patent/CN1705635A/zh
Application granted granted Critical
Publication of CN100448844C publication Critical patent/CN100448844C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
    • C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • 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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • 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
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/77—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
    • C07C233/80—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/84—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
    • C07C237/40—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • C07D209/16—Tryptamines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/40—Acylated substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
    • C07D213/46—Oxygen atoms
    • C07D213/50—Ketonic radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D249/14—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C07D277/82—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
    • C07D317/66—Nitrogen atoms not forming part of a nitro radical
    • 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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Epidemiology (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pyridine Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Indole Compounds (AREA)
CNB2003801016717A 2002-10-17 2003-10-16 组蛋白脱乙酰酶抑制剂 Expired - Fee Related CN100448844C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US41968802P 2002-10-17 2002-10-17
US60/419,688 2002-10-17

Publications (2)

Publication Number Publication Date
CN1705635A CN1705635A (zh) 2005-12-07
CN100448844C true CN100448844C (zh) 2009-01-07

Family

ID=32108128

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB2003801016717A Expired - Fee Related CN100448844C (zh) 2002-10-17 2003-10-16 组蛋白脱乙酰酶抑制剂

Country Status (8)

Country Link
US (2) US7282608B2 (https=)
EP (1) EP1551795A1 (https=)
JP (1) JP2006503082A (https=)
KR (1) KR20050074487A (https=)
CN (1) CN100448844C (https=)
AU (1) AU2003273701A1 (https=)
CA (1) CA2501265A1 (https=)
WO (1) WO2004035525A1 (https=)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105037194A (zh) * 2015-05-27 2015-11-11 厦门大学 一系列查尔酮、二氢查尔酮和黄酮化合物及其制备方法和用途

Families Citing this family (74)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6777217B1 (en) 1996-03-26 2004-08-17 President And Fellows Of Harvard College Histone deacetylases, and uses related thereto
US20030129724A1 (en) 2000-03-03 2003-07-10 Grozinger Christina M. Class II human histone deacetylases, and uses related thereto
US7244853B2 (en) 2001-05-09 2007-07-17 President And Fellows Of Harvard College Dioxanes and uses thereof
US7868204B2 (en) * 2001-09-14 2011-01-11 Methylgene Inc. Inhibitors of histone deacetylase
CN101851173A (zh) 2001-09-14 2010-10-06 梅特希尔基因公司 组蛋白脱乙酰化酶抑制剂
US6897220B2 (en) * 2001-09-14 2005-05-24 Methylgene, Inc. Inhibitors of histone deacetylase
US7154002B1 (en) 2002-10-08 2006-12-26 Takeda San Diego, Inc. Histone deacetylase inhibitors
US7250514B1 (en) 2002-10-21 2007-07-31 Takeda San Diego, Inc. Histone deacetylase inhibitors
US7381825B2 (en) 2003-03-17 2008-06-03 Takeda San Diego, Inc. Histone deacetylase inhibitors
WO2005030705A1 (en) * 2003-09-24 2005-04-07 Methylgene, Inc. Inhibitors of histone deacetylase
MXPA06003951A (es) * 2003-10-07 2006-06-27 Renovis Inc Derivados de amida como ligandos del canal de ion y composiciones farmaceuticas y sus metodos de uso.
US7253204B2 (en) * 2004-03-26 2007-08-07 Methylgene Inc. Inhibitors of histone deacetylase
WO2005121073A1 (en) * 2004-06-10 2005-12-22 Cancer Research Technology Limited Inhibitors of histone deacetylase
US7534918B2 (en) * 2004-07-12 2009-05-19 Merck & Co., Inc. Histone deacetylase inhibitors
US7781478B2 (en) 2004-07-14 2010-08-24 Ptc Therapeutics, Inc. Methods for treating hepatitis C
WO2006019831A1 (en) 2004-07-14 2006-02-23 Ptc Therapeutics, Inc. Methods for treating hepatitis c
US7868037B2 (en) 2004-07-14 2011-01-11 Ptc Therapeutics, Inc. Methods for treating hepatitis C
US7772271B2 (en) 2004-07-14 2010-08-10 Ptc Therapeutics, Inc. Methods for treating hepatitis C
WO2006019832A1 (en) 2004-07-22 2006-02-23 Ptc Therapeutics, Inc. Thienopyridines for treating hepatitis c
EP1824831A2 (en) 2004-12-16 2007-08-29 Takeda San Diego, Inc. Histone deacetylase inhibitors
US7576099B2 (en) 2005-02-28 2009-08-18 Renovis, Inc. Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same
EA200701835A1 (ru) * 2005-02-28 2008-02-28 Реновис, Инк. Амидные производные в качестве лигандов ионных каналов, их фармацевтические композиции и способы их применения
US8999289B2 (en) 2005-03-22 2015-04-07 President And Fellows Of Harvard College Treatment of protein degradation disorders
EP1896436A2 (en) 2005-05-11 2008-03-12 Takeda San Diego, Inc. Histone deacetylase inhibitors
KR101378716B1 (ko) 2005-05-20 2014-04-10 메틸진 인코포레이티드 Ｖｅｇｆ 수용체 및 ｈｇｆ 수용체 신호전달의 억제제
EA200800321A1 (ru) 2005-07-14 2008-06-30 Такеда Сан Диего, Инк. Ингибиторы гистондеацетилазы
JP2009521424A (ja) * 2005-12-19 2009-06-04 メチルジーン インコーポレイテッド 抗真菌剤の活性を増強するためのヒストンデアセチラーゼ阻害剤
CN100346830C (zh) * 2005-12-28 2007-11-07 上海交通大学医学院附属瑞金医院 一种治疗b细胞淋巴瘤的药物组合物
JP2009525955A (ja) * 2006-01-13 2009-07-16 タケダ サン ディエゴ インコーポレイテッド ヒストンデアセチラーゼ阻害剤
US8222423B2 (en) 2006-02-14 2012-07-17 Dana-Farber Cancer Institute, Inc. Bifunctional histone deacetylase inhibitors
WO2007095584A2 (en) 2006-02-14 2007-08-23 The President And Fellows Of Harvard College Histone Deacetylase Inhibitors
WO2007100657A2 (en) 2006-02-28 2007-09-07 Merck & Co., Inc. Inhibitors of histone deacetylase
US8304451B2 (en) * 2006-05-03 2012-11-06 President And Fellows Of Harvard College Histone deacetylase and tubulin deacetylase inhibitors
CN105481788A (zh) 2006-10-28 2016-04-13 梅特希尔基因公司 组蛋白脱乙酰酶抑制剂
US8030344B2 (en) 2007-03-13 2011-10-04 Methylgene Inc. Inhibitors of histone deacetylase
JP2008266322A (ja) 2007-03-28 2008-11-06 Santen Pharmaceut Co Ltd ヒストン脱アセチル化酵素阻害作用を有する化合物を有効成分として含有する眼圧下降剤
TWI519508B (zh) 2007-06-12 2016-02-01 Achaogen Inc 抗菌劑
EP2003118A1 (de) * 2007-06-13 2008-12-17 Bayer Schering Pharma Aktiengesellschaft Zimtsäurederivate als Modulatoren des EP2-Rezeptors
AU2008269154B2 (en) 2007-06-27 2014-06-12 Merck Sharp & Dohme Llc 4-carboxybenzylamino derivatives as histone deacetylase inhibitors
EP2170339B1 (en) 2007-06-27 2014-10-15 Merck Sharp & Dohme Corp. Pyridyl and pyrimidinyl derivatives as histone deacetylase inhibitors
JP2011500783A (ja) * 2007-10-22 2011-01-06 オーキッド リサーチ ラボラトリーズ リミテッド ヒストンデアセチラーゼ阻害剤
US20110044952A1 (en) * 2007-11-27 2011-02-24 Ottawa Health Research Institute Amplification of cancer-specific oncolytic viral infection by histone deacetylase inhibitors
WO2009079391A1 (en) * 2007-12-14 2009-06-25 Gilead Colorado, Inc. Benzofuran anilide histone deacetylase inhibitors
US8124764B2 (en) 2008-07-14 2012-02-28 Gilead Sciences, Inc. Fused heterocyclyc inhibitor compounds
CA2729909A1 (en) 2008-07-14 2010-01-21 Gilead Sciences, Inc. Imidazolyl pyrimidine inhibitor compounds
WO2010009166A1 (en) 2008-07-14 2010-01-21 Gilead Colorado, Inc. Oxindolyl inhibitor compounds
AU2009274549B2 (en) * 2008-07-23 2014-05-01 Dana-Farber Cancer Institute, Inc. Deacetylase inhibitors and uses thereof
US8623853B2 (en) 2008-07-23 2014-01-07 The Brigham And Women's Hospital, Inc. Treatment of cancers characterized by chromosomal rearrangement of the NUT gene
CN102123987A (zh) 2008-07-28 2011-07-13 吉里德科学公司 亚环烷基和亚杂环烷基组蛋白脱乙酰酶抑制剂化合物
AU2009289649B2 (en) 2008-09-03 2016-05-05 Biomarin Pharmaceutical Inc. Compositions including 6-aminohexanoic acid derivatives as HDAC inhibitors
ES2599458T3 (es) 2008-10-14 2017-02-01 Sunshine Lake Pharma Co., Ltd. Compuestos y métodos de uso
KR20120031170A (ko) 2009-06-08 2012-03-30 길리애드 사이언시즈, 인코포레이티드 알카노일아미노 벤즈아미드 아닐린 ｈｄａｃ 저해제 화합물
US8283357B2 (en) 2009-06-08 2012-10-09 Gilead Sciences, Inc. Cycloalkylcarbamate benzamide aniline HDAC inhibitor compounds
WO2011019393A2 (en) 2009-08-11 2011-02-17 President And Fellows Of Harvard College Class- and isoform-specific hdac inhibitors and uses thereof
JP2013509441A (ja) 2009-10-30 2013-03-14 マサチューセッツ インスティテュート オブ テクノロジー 記憶／認知および不安障害の処置のためのｃｉ−９９４およびジナリンの使用
EP2523941B1 (en) * 2010-01-12 2014-10-15 Council of Scientific & Industrial Research Imidazolone-chalcone derivatives as potential anticancer agent and process for the preparation thereof
CN102249958B (zh) * 2010-11-29 2014-06-04 江苏先声药物研究有限公司 苯甲酰氨类组蛋白去乙酰化酶抑制剂
RU2568258C2 (ru) 2011-02-28 2015-11-20 Саншайн Лейк Фарма Ко., Лтд Замещенные соединения хинолина и способы их использования
US10059723B2 (en) 2011-02-28 2018-08-28 Biomarin Pharmaceutical Inc. Histone deacetylase inhibitors
US8957066B2 (en) 2011-02-28 2015-02-17 Biomarin Pharmaceutical Inc. Histone deacetylase inhibitors
US9540395B2 (en) 2011-02-28 2017-01-10 Biomarin Pharmaceutical Inc. Histone deacetylase inhibitors
EP2721011B1 (en) 2011-06-20 2017-09-06 Emory University Prostaglandin receptor ep2 antagonists, derivatives, compositions, and uses related thereto
EP2847168A1 (en) 2012-05-10 2015-03-18 Achaogen, Inc. Antibacterial agents
JP6342392B2 (ja) 2012-07-28 2018-06-13 カリター・サイエンシーズ・エルエルシー 置換型ピラゾロン化合物及び使用方法
TWI574962B (zh) 2012-11-14 2017-03-21 加拓科學公司 作爲ｐｉ３激酶調節劑的芳雜環化合物及其使用方法和用途
MX2015010700A (es) 2013-02-21 2017-01-23 Calitor Sciences Llc Compuestos heteroaromaticos como moduladores de la p13 cinasa.
DK2970139T3 (en) 2013-03-15 2018-08-13 Biomarin Pharm Inc HDAC inhibitors
WO2015006875A1 (en) * 2013-07-18 2015-01-22 Methylgene Inc. Process for the preparation of substituted pyrimidines
EP3769757A3 (en) * 2013-10-18 2021-10-06 The General Hospital Corporation Imaging histone deacetylases with a radiotracer using positron emission tomography
US9636298B2 (en) 2014-01-17 2017-05-02 Methylgene Inc. Prodrugs of compounds that enhance antifungal activity and compositions of said prodrugs
EP3137074B1 (en) 2014-04-29 2020-08-05 Emory University Prostaglandin receptor ep2 antagonists, derivatives, compositions, and uses related thereto
US10308658B2 (en) 2015-10-19 2019-06-04 Sunshine Lake Pharma Co., Ltd. Salt of EGFR inhibitor, crystalline form and uses thereof
AU2020242053C1 (en) 2019-03-20 2025-11-13 Emory University Prostaglandin receptor EP2 antagonists, derivatives, and uses related thereto
CN116768815B (zh) * 2023-06-13 2025-04-18 首都医科大学附属北京安定医院 靛红酸酐类化合物及其制备方法和用途

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6174905B1 (en) * 1996-09-30 2001-01-16 Mitsui Chemicals, Inc. Cell differentiation inducer

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5149797A (en) * 1990-02-15 1992-09-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of rna and production of encoded polypeptides
US5652355A (en) * 1992-07-23 1997-07-29 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates
DE19510957A1 (de) 1995-03-25 1996-09-26 Huels Chemische Werke Ag Eingedickter Bodenverfestiger, sowie diesen enthaltende verpackte Fertigmischung für Bodenbehandlungen
EP1748046A3 (en) 1999-11-23 2007-08-22 Methylgene, Inc. Inhibitors of histone deacetylase
WO2001070675A2 (en) 2000-03-24 2001-09-27 Methylgene, Inc. Inhibitors of histone deacetylase

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6174905B1 (en) * 1996-09-30 2001-01-16 Mitsui Chemicals, Inc. Cell differentiation inducer

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
grossmann inhibition of histone deacetylases a new strategy to targetepigenetic modification s for anticancer tratment. ulrich h weidle adelbert.anticancer research,Vol.20. 2000 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105037194A (zh) * 2015-05-27 2015-11-11 厦门大学 一系列查尔酮、二氢查尔酮和黄酮化合物及其制备方法和用途

Also Published As

Publication number Publication date
EP1551795A1 (en) 2005-07-13
JP2006503082A (ja) 2006-01-26
US20090023734A1 (en) 2009-01-22
KR20050074487A (ko) 2005-07-18
CN1705635A (zh) 2005-12-07
WO2004035525A1 (en) 2004-04-29
US20060020131A1 (en) 2006-01-26
CA2501265A1 (en) 2004-04-29
US7282608B2 (en) 2007-10-16
AU2003273701A1 (en) 2004-05-04

Similar Documents

Publication Publication Date Title
CN100448844C (zh) 组蛋白脱乙酰酶抑制剂
JP5746860B2 (ja) ヒストンデアセチラーゼ阻害剤
JP3908773B2 (ja) ヒストンデアセチラーゼの阻害剤
JP4809228B2 (ja) ヒストンデアセチラーゼの阻害剤
CA2465978C (en) Inhibitors of histone deacetylase
EP1099692B1 (en) N,n-substituted cyclic amine derivatives
Deng et al. Discovery of highly potent and selective small molecule ADAMTS-5 inhibitors that inhibit human cartilage degradation via encoded library technology (ELT)
EP1590334B1 (en) 2,4-diaminopyrimidine derivatives useful as inhibitors of pkc-theta
KR101495611B1 (ko) 히스톤 데아세틸라아제의 억제제
US7022731B2 (en) Platelet ADP receptor inhibitors
US20120115827A1 (en) 3-aminobenzamide compounds and vanilloid receptor subtype 1 (vr1) inhibitors
TW201040162A (en) Inhibitors of JAK
CN106946792A (zh) 一种酞嗪酮的异羟肟酸衍生物及其制备方法与应用
CN101445469B (zh) 组蛋白脱乙酰基酶抑制剂
TWI248434B (en) Unsymmetrical cyclic diamine compound
CA1265139A (en) Amides and ester of 2-¬n-(morpholinoalkyl) aminosulfonyl|-nitrobenzoic acids, useful as adjuncts to radiation therapy
CN101072762A (zh) 苯基－哌嗪甲酮衍生物
CN113307791A (zh) 嘧啶基哌嗪脲类trpv1拮抗/mor激动双靶点化合物及其制备方法和应用
CN118063489B (zh) 吴茱萸碱类化合物及其制药用途
UA73995C2 (en) Indole derivatives being useful for the treatment of cns disorders,, a pharmaceutical composition and a method for treatment
TWI415606B (zh) 組蛋白去乙醯基酶之抑制劑
US4845284A (en) Substituted 3-nitrobenzenesulfonamides useful as adjuncts in radiation therapy
JPS63201154A (ja) ２−アミノアセトアミドトリフルオルメチル誘導体

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
C17 Cessation of patent right
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20090107

Termination date: 20091116