CA2532798C - Azepine derivatives as pharmaceutical agents - Google Patents
Azepine derivatives as pharmaceutical agents Download PDFInfo
- Publication number
- CA2532798C CA2532798C CA2532798A CA2532798A CA2532798C CA 2532798 C CA2532798 C CA 2532798C CA 2532798 A CA2532798 A CA 2532798A CA 2532798 A CA2532798 A CA 2532798A CA 2532798 C CA2532798 C CA 2532798C
- Authority
- CA
- Canada
- Prior art keywords
- optionally substituted
- heterocyclyl
- ring
- alkyl
- 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
Links
- 150000001538 azepines Chemical class 0.000 title description 8
- 239000008177 pharmaceutical agent Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 235
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 132
- 239000000203 mixture Substances 0.000 claims abstract description 102
- 201000010099 disease Diseases 0.000 claims abstract description 73
- 230000000694 effects Effects 0.000 claims abstract description 61
- 208000035475 disorder Diseases 0.000 claims abstract description 59
- 208000024891 symptom Diseases 0.000 claims abstract description 30
- 125000000623 heterocyclic group Chemical group 0.000 claims description 238
- 125000001072 heteroaryl group Chemical group 0.000 claims description 229
- 229910052739 hydrogen Inorganic materials 0.000 claims description 214
- 239000001257 hydrogen Substances 0.000 claims description 214
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 200
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 176
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 158
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 146
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 133
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 130
- 125000000217 alkyl group Chemical group 0.000 claims description 127
- 125000003118 aryl group Chemical group 0.000 claims description 114
- -1 cyano, thiocyano Chemical group 0.000 claims description 113
- 125000005843 halogen group Chemical group 0.000 claims description 103
- 125000003107 substituted aryl group Chemical group 0.000 claims description 103
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 84
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 83
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 78
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 70
- 125000003342 alkenyl group Chemical group 0.000 claims description 67
- 229910052799 carbon Inorganic materials 0.000 claims description 60
- 229910052757 nitrogen Inorganic materials 0.000 claims description 55
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 53
- 125000000304 alkynyl group Chemical group 0.000 claims description 50
- 125000004432 carbon atom Chemical group C* 0.000 claims description 47
- 102100038495 Bile acid receptor Human genes 0.000 claims description 46
- 101000603876 Homo sapiens Bile acid receptor Proteins 0.000 claims description 43
- 125000001188 haloalkyl group Chemical group 0.000 claims description 39
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 38
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 32
- 150000001721 carbon Chemical group 0.000 claims description 31
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 26
- 125000002577 pseudohalo group Chemical group 0.000 claims description 22
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- 125000002947 alkylene group Chemical group 0.000 claims description 20
- 206010012601 diabetes mellitus Diseases 0.000 claims description 20
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- 125000004429 atom Chemical group 0.000 claims description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
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- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 18
- 239000003937 drug carrier Substances 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 125000004043 oxo group Chemical group O=* 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 16
- 206010008635 Cholestasis Diseases 0.000 claims description 15
- 230000007870 cholestasis Effects 0.000 claims description 15
- 231100000359 cholestasis Toxicity 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 14
- 102000004877 Insulin Human genes 0.000 claims description 14
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- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 14
- 229940125396 insulin Drugs 0.000 claims description 14
- 208000008589 Obesity Diseases 0.000 claims description 13
- 201000001421 hyperglycemia Diseases 0.000 claims description 13
- 235000020824 obesity Nutrition 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 12
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 12
- 206010049287 Lipodystrophy acquired Diseases 0.000 claims description 12
- 125000001118 alkylidene group Chemical group 0.000 claims description 12
- 208000006132 lipodystrophy Diseases 0.000 claims description 12
- 239000000651 prodrug Substances 0.000 claims description 12
- 229940002612 prodrug Drugs 0.000 claims description 12
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 11
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 10
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- 208000011580 syndromic disease Diseases 0.000 claims description 9
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- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 8
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 8
- 125000002462 isocyano group Chemical group *[N+]#[C-] 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 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 claims description 2
- 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 claims description 2
- JZLZVIJITPGHLC-UHFFFAOYSA-N ethyl 3-(4-fluorobenzoyl)-1,1-dimethyl-2,6,7,8,9,10-hexahydroazepino[4,5-b]indole-5-carboxylate Chemical compound C1C(C)(C)C=2C=3CCCCC=3NC=2C(C(=O)OCC)=CN1C(=O)C1=CC=C(F)C=C1 JZLZVIJITPGHLC-UHFFFAOYSA-N 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 8
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims 4
- SPJUIDRZQNWSFO-UHFFFAOYSA-N 2-o-ethyl 8-o-propan-2-yl 6-(3,4-difluorobenzoyl)-1,4,4-trimethyl-5h-pyrrolo[2,3-d]azepine-2,8-dicarboxylate Chemical compound CN1C(C(=O)OCC)=CC(C(C2)(C)C)=C1C(C(=O)OC(C)C)=CN2C(=O)C1=CC=C(F)C(F)=C1 SPJUIDRZQNWSFO-UHFFFAOYSA-N 0.000 claims 1
- UECMFNQUJCCQOC-UHFFFAOYSA-N 2-o-ethyl 8-o-propan-2-yl 6-(3,4-difluorobenzoyl)-4,4-dimethyl-1,5-dihydropyrrolo[2,3-d]azepine-2,8-dicarboxylate Chemical compound N1C(C(=O)OCC)=CC(C(C2)(C)C)=C1C(C(=O)OC(C)C)=CN2C(=O)C1=CC=C(F)C(F)=C1 UECMFNQUJCCQOC-UHFFFAOYSA-N 0.000 claims 1
- ZVJNUNPODYKBIH-UHFFFAOYSA-N diethyl 6-(3,4-difluorobenzoyl)-4,4-dimethyl-1,5-dihydropyrrolo[2,3-d]azepine-2,8-dicarboxylate Chemical compound N1C(C(=O)OCC)=CC(C(C2)(C)C)=C1C(C(=O)OCC)=CN2C(=O)C1=CC=C(F)C(F)=C1 ZVJNUNPODYKBIH-UHFFFAOYSA-N 0.000 claims 1
- UAKXBPBHABHUMZ-UHFFFAOYSA-N ethyl 3-(4-fluorobenzoyl)-2,4,5,6,7,8,9,10-octahydro-1h-azepino[4,5-b]indole-5-carboxylate Chemical compound C1CC=2C=3CCCCC=3NC=2C(C(=O)OCC)CN1C(=O)C1=CC=C(F)C=C1 UAKXBPBHABHUMZ-UHFFFAOYSA-N 0.000 claims 1
- WEMWNNNXMBXARK-UHFFFAOYSA-N ethyl 3-(4-fluorobenzoyl)-2,6,7,8,9,10-hexahydro-1h-azepino[4,5-b]indole-5-carboxylate Chemical compound C1CC=2C=3CCCCC=3NC=2C(C(=O)OCC)=CN1C(=O)C1=CC=C(F)C=C1 WEMWNNNXMBXARK-UHFFFAOYSA-N 0.000 claims 1
- NUMCHXNUNIYTQB-UHFFFAOYSA-N ethyl 6-(3,4-difluorobenzoyl)-4,4-dimethyl-5h-thieno[2,3-d]azepine-8-carboxylate Chemical compound C1C(C)(C)C=2C=CSC=2C(C(=O)OCC)=CN1C(=O)C1=CC=C(F)C(F)=C1 NUMCHXNUNIYTQB-UHFFFAOYSA-N 0.000 claims 1
- UNHUSZZZKDCSFH-UHFFFAOYSA-N ethyl 6-(3,4-difluorobenzoyl)-4,5-dihydrothieno[2,3-d]azepine-8-carboxylate Chemical compound C1CC=2C=CSC=2C(C(=O)OCC)=CN1C(=O)C1=CC=C(F)C(F)=C1 UNHUSZZZKDCSFH-UHFFFAOYSA-N 0.000 claims 1
- XGRGDOIDUKQZFU-UHFFFAOYSA-N ethyl 6-(4-fluorobenzoyl)-7,8-dihydro-1h-imidazo[4,5-d]azepine-4-carboxylate Chemical compound C1CC=2N=CNC=2C(C(=O)OCC)=CN1C(=O)C1=CC=C(F)C=C1 XGRGDOIDUKQZFU-UHFFFAOYSA-N 0.000 claims 1
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- 239000012177 spermaceti Substances 0.000 description 1
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- 238000011146 sterile filtration Methods 0.000 description 1
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- 125000005717 substituted cycloalkylene group Chemical group 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 150000003455 sulfinic acids Chemical class 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 230000035923 taste sensation Effects 0.000 description 1
- 229920001897 terpolymer Polymers 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 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 1
- ZUHZGEOKBKGPSW-UHFFFAOYSA-N tetraglyme Chemical compound COCCOCCOCCOCCOC ZUHZGEOKBKGPSW-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
- 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 150000003549 thiazolines Chemical class 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 235000019303 thiodipropionic acid Nutrition 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 108091008023 transcriptional regulators Proteins 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical group CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 229940035936 ubiquinone Drugs 0.000 description 1
- 229920011532 unplasticized polyvinyl chloride Polymers 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical class CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 208000030401 vitamin deficiency disease Diseases 0.000 description 1
- 239000008136 water-miscible vehicle Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- 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
- A61P9/10—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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US48985403P | 2003-07-23 | 2003-07-23 | |
| US60/489,854 | 2003-07-23 | ||
| PCT/US2004/023745 WO2005009387A2 (en) | 2003-07-23 | 2004-07-23 | Azepine derivatives as pharmaceutical agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2532798A1 CA2532798A1 (en) | 2005-02-03 |
| CA2532798C true CA2532798C (en) | 2013-02-19 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2532798A Expired - Fee Related CA2532798C (en) | 2003-07-23 | 2004-07-23 | Azepine derivatives as pharmaceutical agents |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US8466143B2 (enExample) |
| EP (1) | EP1648408A4 (enExample) |
| JP (1) | JP4679517B2 (enExample) |
| KR (1) | KR20060052867A (enExample) |
| CN (1) | CN1852748A (enExample) |
| AU (1) | AU2004259009A1 (enExample) |
| BR (1) | BRPI0412262A (enExample) |
| CA (1) | CA2532798C (enExample) |
| CR (1) | CR8258A (enExample) |
| EC (1) | ECSP066392A (enExample) |
| IL (1) | IL173287A0 (enExample) |
| NO (1) | NO20060871L (enExample) |
| RU (1) | RU2006105646A (enExample) |
| WO (1) | WO2005009387A2 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7595311B2 (en) * | 2002-05-24 | 2009-09-29 | Exelixis, Inc. | Azepinoindole derivatives as pharmaceutical agents |
| SG146683A1 (en) | 2003-09-17 | 2008-10-30 | Janssen Pharmaceutica Nv | Fused heterocyclic compounds as serotonin receptor modulators |
| KR20070113225A (ko) | 2005-03-14 | 2007-11-28 | 글락소 그룹 리미티드 | 히스타민 ｈ３ 수용체에 대해 친화성을 갖는 융합된 티아졸유도체 |
| WO2007070796A1 (en) * | 2005-12-15 | 2007-06-21 | Exelixis, Inc. | Azepinoindole derivatives as pharmaceutical agents |
| US20080299118A1 (en) * | 2007-06-01 | 2008-12-04 | Wyeth | FXR Agonists for the Treatment of Malignancies |
| US20080300235A1 (en) * | 2007-06-01 | 2008-12-04 | Wyeth | FXR Agonists for Reducing LOX-1 Expression |
| US20090163474A1 (en) * | 2007-10-19 | 2009-06-25 | Wyeth | FXR Agonists for the Treatment of Nonalcoholic Fatty Liver and Cholesterol Gallstone Diseases |
| US20090215748A1 (en) * | 2007-12-20 | 2009-08-27 | Wyeth | FXR agonists for treating vitamin D associated diseases |
| AR073923A1 (es) * | 2008-10-31 | 2010-12-09 | Medivation Technologies Inc | Pirido( 4,3-b) indoles que contienen restos rigidos |
| CN102316732B (zh) | 2008-10-31 | 2015-04-01 | 梅迪维新技术公司 | 氮杂*并[4,5-b]吲哚以及使用方法 |
| CN101875627B (zh) * | 2009-04-30 | 2014-01-15 | 凯惠科技发展(上海)有限公司 | 一种1-烷氧羰基-2h-异吲哚衍生物及其制备方法和中间体 |
| ES2423668T3 (es) | 2009-05-22 | 2013-09-23 | Abbvie Inc. | Moduladores de receptores 5-HT y métodos de uso de los mismos |
| US9040519B2 (en) | 2010-02-18 | 2015-05-26 | Medivation Technologies, Inc. | Fused tetracyclic pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use |
| US9193728B2 (en) | 2010-02-18 | 2015-11-24 | Medivation Technologies, Inc. | Fused tetracyclic pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use |
| US9034865B2 (en) | 2010-02-18 | 2015-05-19 | Medivation Technologies, Inc. | Pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use |
| WO2011146089A1 (en) | 2010-05-21 | 2011-11-24 | Abbott Laboratories | Modulators of 5-ht receptors and methods of use thereof |
| CA2829045A1 (en) | 2011-02-18 | 2012-08-23 | Medivation Technologies, Inc. | Compounds and methods for treatment of hypertension |
| WO2012112965A1 (en) * | 2011-02-18 | 2012-08-23 | Medivation Technologies, Inc. | Compounds and methods of treating diabetes |
| WO2014031167A1 (en) * | 2012-08-22 | 2014-02-27 | Medivation Technologies, Inc. | Compounds and methods for treatment of hypertension |
| CA2968434A1 (en) * | 2014-11-21 | 2016-05-26 | Akarna Therapeutics, Ltd. | Fused bicyclic compounds for the treatment of disease |
| RU2741387C2 (ru) * | 2014-12-22 | 2021-01-25 | Акарна Терапьютикс, Лтд. | Конденсированные бициклические соединения для лечения заболевания |
| TWI698430B (zh) * | 2015-02-13 | 2020-07-11 | 南北兄弟藥業投資有限公司 | 三環化合物及其在藥物中的應用 |
| RU2021107054A (ru) * | 2015-03-26 | 2021-03-31 | Акарна Терапьютикс, Лтд. | Конденсированные бициклические соединения для лечения заболевания |
| WO2017143134A1 (en) * | 2016-02-19 | 2017-08-24 | Alios Biopharma, Inc. | Fxr modulators and methods of their use |
| JP2019520335A (ja) * | 2016-05-25 | 2019-07-18 | アカーナ・セラピューティクス・リミテッドＡｋａｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｌｔｄ． | 疾患治療用の縮合二環式化合物 |
| MX2018014024A (es) * | 2016-05-25 | 2019-08-29 | Akarna Therapeutics Ltd | Terapias de combinación con moduladores del receptor x farnesoide (fxr). |
| BR112019025228A2 (pt) * | 2017-06-02 | 2020-06-23 | Akarna Therapeutics, Ltd. | Compostos bicíclicos fundidos |
| AU2019212800B2 (en) * | 2018-01-26 | 2024-05-23 | Exelixis, Inc. | Compounds for the treatment of kinase-dependent disorders |
| SG11202006945PA (en) | 2018-01-26 | 2020-08-28 | Exelixis Inc | Compounds for the treatment of kinase-dependent disorders |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GR35044B (el) | 1966-05-10 | 1968-07-31 | The Upjohn Company | Μεθοδος παρασκευης οργανικων ενωσεων. |
| US4362739A (en) * | 1981-05-04 | 1982-12-07 | S.A. Omnichem | Pyrrolo(2,3-d)carbazole derivatives, compositions and use |
| IL101851A (en) * | 1991-06-13 | 1996-05-14 | Janssen Pharmaceutica Nv | 10-(4-piperidinyl- and piperidinylidene)-imidazo [1,2-a] (pyrrolo thieno or furano) [2,3] azepine derivatives their preparation and pharmaceutical compositions containing them and certain novel intermediates therefor |
| JPH09221475A (ja) * | 1996-02-13 | 1997-08-26 | Yamanouchi Pharmaceut Co Ltd | 新規なオキシム誘導体 |
| CA2297988A1 (en) * | 1997-08-04 | 1999-02-11 | Amgen Inc. | Hydroxamic acid substituted fused heterocyclic metalloproteinase inhibitors |
| EP1190065A2 (en) | 1999-06-18 | 2002-03-27 | Cv Therapeutics, Inc. | Atp binding cassette transporter protein abc1 polypeptides |
| FR2796070B1 (fr) * | 1999-07-06 | 2003-02-21 | Lipha | Derives de benzodiazepines utilisables dans le traitement de dyslipidemies, de l'atherosclerose et du diabete, compositions pharmaceutiques les contenant et procedes de preparation |
| MY122278A (en) | 1999-07-19 | 2006-04-29 | Upjohn Co | 1,2,3,4,5,6-hexahydroazepino[4,5-b]indoles containing arylsulfones at the 9-position |
| US20020013334A1 (en) * | 2000-06-15 | 2002-01-31 | Robl Jeffrey A. | HMG-CoA reductase inhibitors and method |
| US7595311B2 (en) * | 2002-05-24 | 2009-09-29 | Exelixis, Inc. | Azepinoindole derivatives as pharmaceutical agents |
| TWI329111B (en) * | 2002-05-24 | 2010-08-21 | X Ceptor Therapeutics Inc | Azepinoindole and pyridoindole derivatives as pharmaceutical agents |
| WO2007070796A1 (en) * | 2005-12-15 | 2007-06-21 | Exelixis, Inc. | Azepinoindole derivatives as pharmaceutical agents |
-
2004
- 2004-07-23 WO PCT/US2004/023745 patent/WO2005009387A2/en not_active Ceased
- 2004-07-23 CA CA2532798A patent/CA2532798C/en not_active Expired - Fee Related
- 2004-07-23 BR BRPI0412262-3A patent/BRPI0412262A/pt not_active IP Right Cessation
- 2004-07-23 KR KR1020067001566A patent/KR20060052867A/ko not_active Withdrawn
- 2004-07-23 US US10/565,702 patent/US8466143B2/en active Active
- 2004-07-23 AU AU2004259009A patent/AU2004259009A1/en not_active Abandoned
- 2004-07-23 JP JP2006521272A patent/JP4679517B2/ja not_active Expired - Fee Related
- 2004-07-23 CN CNA2004800270768A patent/CN1852748A/zh active Pending
- 2004-07-23 EP EP04779004A patent/EP1648408A4/en not_active Withdrawn
- 2004-07-23 RU RU2006105646/04A patent/RU2006105646A/ru not_active Application Discontinuation
-
2006
- 2006-01-22 IL IL173287A patent/IL173287A0/en unknown
- 2006-02-22 NO NO20060871A patent/NO20060871L/no not_active Application Discontinuation
- 2006-02-23 CR CR8258A patent/CR8258A/es not_active Application Discontinuation
- 2006-02-23 EC EC2006006392A patent/ECSP066392A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CR8258A (es) | 2006-08-30 |
| JP4679517B2 (ja) | 2011-04-27 |
| KR20060052867A (ko) | 2006-05-19 |
| CA2532798A1 (en) | 2005-02-03 |
| NO20060871L (no) | 2006-04-24 |
| BRPI0412262A (pt) | 2006-09-19 |
| CN1852748A (zh) | 2006-10-25 |
| JP2006528637A (ja) | 2006-12-21 |
| US8466143B2 (en) | 2013-06-18 |
| EP1648408A4 (en) | 2006-11-29 |
| WO2005009387A3 (en) | 2006-03-02 |
| WO2005009387A2 (en) | 2005-02-03 |
| RU2006105646A (ru) | 2007-09-10 |
| EP1648408A1 (en) | 2006-04-26 |
| AU2004259009A1 (en) | 2005-02-03 |
| US20070015746A1 (en) | 2007-01-18 |
| IL173287A0 (en) | 2006-06-11 |
| ECSP066392A (enExample) | 2007-01-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20160725 |