ES2379658T3 - Derivados de bencilpiperazina como antagonistas del receptor de motilina - Google Patents
Derivados de bencilpiperazina como antagonistas del receptor de motilina Download PDFInfo
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- ES2379658T3 ES2379658T3 ES07765418T ES07765418T ES2379658T3 ES 2379658 T3 ES2379658 T3 ES 2379658T3 ES 07765418 T ES07765418 T ES 07765418T ES 07765418 T ES07765418 T ES 07765418T ES 2379658 T3 ES2379658 T3 ES 2379658T3
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- Prior art keywords
- methyl
- phenyl
- amino
- compound
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- 102000057413 Motilin receptors Human genes 0.000 title description 7
- 108700040483 Motilin receptors Proteins 0.000 title description 7
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical class C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 title description 3
- 239000002464 receptor antagonist Substances 0.000 title 1
- 229940044551 receptor antagonist Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 205
- 238000000034 method Methods 0.000 claims abstract description 69
- 238000011282 treatment Methods 0.000 claims abstract description 26
- 101001132878 Homo sapiens Motilin receptor Proteins 0.000 claims abstract description 21
- 102100033818 Motilin receptor Human genes 0.000 claims abstract description 21
- 238000002360 preparation method Methods 0.000 claims abstract description 20
- 230000008569 process Effects 0.000 claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 230000001404 mediated effect Effects 0.000 claims abstract description 6
- -1 nitro , cyano, phenyl Chemical group 0.000 claims description 78
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 62
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 52
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 46
- 239000002904 solvent Substances 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 33
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 29
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 25
- 208000035475 disorder Diseases 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 10
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 9
- 208000011231 Crohn disease Diseases 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 201000006549 dyspepsia Diseases 0.000 claims description 7
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 7
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- 206010021518 Impaired gastric emptying Diseases 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 208000001288 gastroparesis Diseases 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 6
- 230000009467 reduction Effects 0.000 claims description 6
- 238000006722 reduction reaction Methods 0.000 claims description 6
- 238000006268 reductive amination reaction Methods 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 5
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 5
- 206010006895 Cachexia Diseases 0.000 claims description 5
- 206010010774 Constipation Diseases 0.000 claims description 5
- 206010052405 Gastric hypomotility Diseases 0.000 claims description 5
- 206010021639 Incontinence Diseases 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 208000003243 intestinal obstruction Diseases 0.000 claims description 5
- 230000001769 paralizing effect Effects 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 238000001356 surgical procedure Methods 0.000 claims description 5
- 208000014997 Crohn colitis Diseases 0.000 claims description 4
- 206010047700 Vomiting Diseases 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 3
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
- 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 claims description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 3
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000565 sulfonamide group Chemical group 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 239000004202 carbamide Substances 0.000 claims description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 75
- 239000000243 solution Substances 0.000 description 52
- 239000000203 mixture Substances 0.000 description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 28
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- 238000004440 column chromatography Methods 0.000 description 26
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 25
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- 239000003643 water by type Substances 0.000 description 21
- 239000010410 layer Substances 0.000 description 20
- 230000000694 effects Effects 0.000 description 18
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000012043 crude product Substances 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical class O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 13
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 13
- 239000012279 sodium borohydride Substances 0.000 description 13
- 229910000033 sodium borohydride Inorganic materials 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 238000010828 elution Methods 0.000 description 11
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 11
- 101800002372 Motilin Proteins 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 239000000556 agonist Substances 0.000 description 10
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- LVRVABPNVHYXRT-BQWXUCBYSA-N 52906-92-0 Chemical compound C([C@H](N)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O)C(C)C)C1=CC=CC=C1 LVRVABPNVHYXRT-BQWXUCBYSA-N 0.000 description 9
- 150000001793 charged compounds Chemical class 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Inorganic materials [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- 239000003981 vehicle Substances 0.000 description 9
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 8
- 102000002419 Motilin Human genes 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 7
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- OLIDKJBMRLAXQA-UHFFFAOYSA-N n-(3-fluorophenyl)piperidin-4-amine Chemical compound FC1=CC=CC(NC2CCNCC2)=C1 OLIDKJBMRLAXQA-UHFFFAOYSA-N 0.000 description 7
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- 238000012360 testing method Methods 0.000 description 6
- BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
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- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Inorganic materials O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 5
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Classifications
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- 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
- C07D211/36—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 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- 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
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- 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
- A61P1/10—Laxatives
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- 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
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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- 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
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- 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
- 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
-
- 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
- C07D211/34—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D211/36—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 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Nutrition Science (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0611907 | 2006-06-15 | ||
| GBGB0611907.7A GB0611907D0 (en) | 2006-06-15 | 2006-06-15 | Compounds |
| PCT/EP2007/055890 WO2007144400A1 (en) | 2006-06-15 | 2007-06-14 | Benzylpiperazine derivatives as motilin receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2379658T3 true ES2379658T3 (es) | 2012-04-30 |
Family
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Family Applications (1)
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|---|---|---|---|
| ES07765418T Active ES2379658T3 (es) | 2006-06-15 | 2007-06-14 | Derivados de bencilpiperazina como antagonistas del receptor de motilina |
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| US (2) | US8012981B2 (enExample) |
| EP (1) | EP2029538B1 (enExample) |
| JP (1) | JP5232143B2 (enExample) |
| AT (1) | ATE542795T1 (enExample) |
| ES (1) | ES2379658T3 (enExample) |
| GB (1) | GB0611907D0 (enExample) |
| WO (1) | WO2007144400A1 (enExample) |
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| GB0611907D0 (en) * | 2006-06-15 | 2006-07-26 | Glaxo Group Ltd | Compounds |
| DK1907374T3 (da) | 2005-07-26 | 2012-10-15 | Glaxo Group Ltd | Til behandling af gastrointestinale sygdomme anvendelige benzylpiperazin-derivater |
| GB0524814D0 (en) * | 2005-12-05 | 2006-01-11 | Glaxo Group Ltd | Compounds |
| PT2041093E (pt) | 2006-06-28 | 2010-06-28 | Glaxo Group Ltd | Derivados de piperazinilo úteis no tratamento de doenças mediadas pelo receptor gpr38 |
| WO2009086485A1 (en) | 2007-12-28 | 2009-07-09 | Server Technology, Inc. | Power distribution, management, and monitoring systems and methods |
| WO2010102150A1 (en) | 2009-03-04 | 2010-09-10 | Server Technology, Inc. | Monitoring power-related parameters in a power distribution unit |
| US9452980B2 (en) | 2009-12-22 | 2016-09-27 | Hoffmann-La Roche Inc. | Substituted benzamides |
| EP2560658B1 (en) | 2010-04-21 | 2017-02-22 | VentiRx Pharmaceuticals, Inc. | Enhancing antibody-dependent cellular cytotoxicity |
| DK2623492T3 (da) * | 2010-09-27 | 2014-08-11 | Daiichi Sankyo Co Ltd | Cyclohexanderivatforbindelse |
| WO2012109267A2 (en) | 2011-02-07 | 2012-08-16 | The Trustees Of The University Of Pennsylvania | Novel peptides and methods using same |
| CN108713019B (zh) | 2016-03-17 | 2021-06-15 | 豪夫迈·罗氏有限公司 | 具有作为taar的激动剂的活性的5-乙基-4-甲基-吡唑-3-甲酰胺衍生物 |
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| CA2105655A1 (en) | 1991-03-08 | 1992-09-09 | Kent Neuenschwander | Multicyclic tertiary amine polyaromatic squalene synthetase inhibitors |
| US5385912A (en) * | 1991-03-08 | 1995-01-31 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Multicyclic tertiary amine polyaromatic squalene synthase inhibitors |
| JPH06211886A (ja) | 1992-11-04 | 1994-08-02 | Chugai Pharmaceut Co Ltd | エリスロマイシン誘導体 |
| TW355711B (en) | 1992-11-04 | 1999-04-11 | Chugai Pharmaceutical Co Ltd | Erythromycin derivatives |
| US5593994A (en) * | 1994-09-29 | 1997-01-14 | The Dupont Merck Pharmaceutical Company | Prostaglandin synthase inhibitors |
| JP3901239B2 (ja) | 1996-03-13 | 2007-04-04 | 大正製薬株式会社 | アリールアルカン誘導体 |
| JP2000508631A (ja) | 1996-04-03 | 2000-07-11 | メルク エンド カンパニー インコーポレーテッド | ファルネシルタンパク質トランスフェラーゼの阻害剤 |
| US5965578A (en) * | 1996-04-03 | 1999-10-12 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| DE19644195A1 (de) * | 1996-10-24 | 1998-04-30 | Solvay Pharm Gmbh | 10,13,15-Trioxatricyclo[9.2.1.1.·9·.·6·]-pentadecanon-Derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel |
| US6100239A (en) * | 1996-11-26 | 2000-08-08 | Chugai Seiyaku Kabushiki Kaisha | 13-membered ring macrolide compound, medicine containing the same, and process for producing the same |
| US6060491A (en) * | 1997-06-19 | 2000-05-09 | Dupont Pharmaceuticals | 6-membered aromatics as factor Xa inhibitors |
| US5972939A (en) * | 1997-10-28 | 1999-10-26 | Ortho-Mcneil Pharmaceutical, Inc. | Cyclopentene derivatives useful as antagonists of the motilin receptor |
| US6165985A (en) * | 1998-02-13 | 2000-12-26 | Solvay Pharmaceuticals Gmbh | 11-acetyl-12,13-dioxabicyclo[8.2.1]-tridecenone derivatives, processes for their preparation and pharmaceutical compositions comprising them |
| DE19805822B4 (de) | 1998-02-13 | 2009-02-05 | Solvay Pharmaceuticals Gmbh | 11-Acetyl-12,13-dioxabicyclo[8.2.1]tridecenon-Derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel |
| GB9804734D0 (en) * | 1998-03-05 | 1998-04-29 | Pfizer Ltd | Compounds |
| US20020010184A1 (en) | 2000-02-18 | 2002-01-24 | Dinsmore Christopher J. | Inhibitors of prenyl-protein transferase |
| US20020052380A1 (en) * | 2000-02-18 | 2002-05-02 | Dinsmore Christopher J. | Inhibitors of prenyl-protein transferase |
| US6384031B2 (en) * | 2000-03-13 | 2002-05-07 | Ortho-Mcneil Pharmaceutical, Inc. | Cyclobutene derivatives useful as antagonists of the motilin receptor |
| WO2001068621A1 (en) * | 2000-03-13 | 2001-09-20 | Ortho-Mcneil Pharmaceutical, Inc. | Novel cyclohexene derivatives useful as antagonists of the motilin receptor |
| WO2001068620A1 (en) | 2000-03-13 | 2001-09-20 | Ortho-Mcneil Pharmaceutical, Inc. | Novel cyclopentene derivatives useful as antagonists of the motilin receptor |
| US6511980B2 (en) * | 2000-05-05 | 2003-01-28 | Ortho Mcneil Pharmaceutical, Inc. | Substituted diamine derivatives useful as motilin antagonists |
| US7102009B2 (en) * | 2001-01-12 | 2006-09-05 | Amgen Inc. | Substituted amine derivatives and methods of use |
| WO2002092592A1 (de) | 2001-05-10 | 2002-11-21 | Solvay Pharmaceuticals Gmbh | Neue 1-amidomethylcarbonyl-piperidinderivate, verfahren und zwischenprodukte zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| US6977264B2 (en) * | 2001-07-25 | 2005-12-20 | Amgen Inc. | Substituted piperidines and methods of use |
| JP2006505590A (ja) * | 2002-10-23 | 2006-02-16 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ヒスタミンｈ３受容体調節物質としてのフェニルピペリジンおよびフェニルピロリジン |
| US7223788B2 (en) * | 2003-02-14 | 2007-05-29 | Sanofi-Aventis Deutschland Gmbh | Substituted N-aryl heterocycles, process for their preparation and their use as medicaments |
| US7262195B2 (en) | 2003-09-17 | 2007-08-28 | Bristol-Myers Squibb Company | Compounds useful as motilin agonists and method |
| US7338954B2 (en) * | 2003-09-17 | 2008-03-04 | Bristol-Myers Squibb Company | Compounds useful as motilin agonists and method |
| WO2005063720A1 (ja) | 2003-12-25 | 2005-07-14 | Nippon Shinyaku Co., Ltd. | アミド誘導体及び医薬 |
| WO2005077373A2 (en) | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Treatment of gastro-esophageal reflux disease (gerd) |
| WO2005077345A1 (en) | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Compounds for the treatment of gastro-esophageal reflux disease |
| WO2005077368A2 (en) | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Treatment of gastro-esophageal reflux disease (gerd) |
| EP1732549A4 (en) * | 2004-03-18 | 2009-11-11 | Brigham & Womens Hospital | METHOD FOR THE TREATMENT OF SYNUCLEINOPATHIES |
| WO2005089515A2 (en) * | 2004-03-18 | 2005-09-29 | The Brigham And Women's Hospital, Inc. | Methods for the treatment of synucleinopathies |
| US20070293539A1 (en) * | 2004-03-18 | 2007-12-20 | Lansbury Peter T | Methods for the treatment of synucleinopathies |
| JP2007538004A (ja) * | 2004-03-18 | 2007-12-27 | ザ ブライハム アンド ウイメンズ ホスピタル， インコーポレイテッド | シヌクレイノパチーを治療する方法 |
| WO2005089502A2 (en) | 2004-03-18 | 2005-09-29 | The Brigham And Women's Hospital, Inc. | Methods for the treatment of synucleinopathies |
| SE0401345D0 (sv) * | 2004-05-25 | 2004-05-25 | Astrazeneca Ab | Therapeutic compounds: Pyridine as scaffold |
| SE0401970D0 (sv) | 2004-08-02 | 2004-08-02 | Astrazeneca Ab | Novel compounds |
| GB0611907D0 (en) * | 2006-06-15 | 2006-07-26 | Glaxo Group Ltd | Compounds |
| US20080312209A1 (en) | 2005-07-12 | 2008-12-18 | Glaxo Group Limited | Piperazine Heteroaryl Derivatives as Gpr38 Agonists |
| DK1907374T3 (da) * | 2005-07-26 | 2012-10-15 | Glaxo Group Ltd | Til behandling af gastrointestinale sygdomme anvendelige benzylpiperazin-derivater |
| GB0524814D0 (en) * | 2005-12-05 | 2006-01-11 | Glaxo Group Ltd | Compounds |
| PT2041093E (pt) * | 2006-06-28 | 2010-06-28 | Glaxo Group Ltd | Derivados de piperazinilo úteis no tratamento de doenças mediadas pelo receptor gpr38 |
| GB0723317D0 (en) * | 2007-11-28 | 2008-01-09 | Glaxo Group Ltd | Compounds |
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2006
- 2006-06-15 GB GBGB0611907.7A patent/GB0611907D0/en not_active Ceased
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2007
- 2007-06-14 WO PCT/EP2007/055890 patent/WO2007144400A1/en not_active Ceased
- 2007-06-14 EP EP07765418A patent/EP2029538B1/en active Active
- 2007-06-14 US US12/304,539 patent/US8012981B2/en not_active Expired - Fee Related
- 2007-06-14 AT AT07765418T patent/ATE542795T1/de active
- 2007-06-14 ES ES07765418T patent/ES2379658T3/es active Active
- 2007-06-14 JP JP2009514801A patent/JP5232143B2/ja not_active Expired - Fee Related
-
2011
- 2011-07-20 US US13/186,869 patent/US8236953B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP2029538B1 (en) | 2012-01-25 |
| WO2007144400A1 (en) | 2007-12-21 |
| GB0611907D0 (en) | 2006-07-26 |
| JP5232143B2 (ja) | 2013-07-10 |
| EP2029538A1 (en) | 2009-03-04 |
| ATE542795T1 (de) | 2012-02-15 |
| US8012981B2 (en) | 2011-09-06 |
| US20110275815A1 (en) | 2011-11-10 |
| US8236953B2 (en) | 2012-08-07 |
| JP2009539938A (ja) | 2009-11-19 |
| US20090131453A1 (en) | 2009-05-21 |
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