CA2147503A1 - Analogues de dipeptides substitues stimulant la liberation de l'hormone de croissance - Google Patents

Analogues de dipeptides substitues stimulant la liberation de l'hormone de croissance

Info

Publication number: CA2147503A1
Authority: CA; Canada
Prior art keywords: amino; methyl; biphenyl; alkyl; alpha
Prior art date: 1992-11-06
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.): Abandoned

Application number

CA002147503A

Other languages

English (en)

Inventor

Judith M. Pisano

William R. Schoen

Matthew J. Wyvratt

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.)

Merck and Co Inc

Original Assignee

Individual

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.)

1992-11-06

Filing date

1993-10-29

Publication date

1994-05-26

1993-10-29 Application filed by Individual filed Critical Individual

1994-05-26 Publication of CA2147503A1 publication Critical patent/CA2147503A1/fr

Status Abandoned legal-status Critical Current

Links

102000018997 Growth Hormone Human genes 0.000 title claims abstract description 46
108010051696 Growth Hormone Proteins 0.000 title claims abstract description 46
239000000122 growth hormone Substances 0.000 title claims abstract description 46
108010016626 Dipeptides Proteins 0.000 title abstract description 11
150000001875 compounds Chemical class 0.000 claims abstract description 70
239000000203 mixture Substances 0.000 claims abstract description 51
238000004519 manufacturing process Methods 0.000 claims abstract description 7
241001465754 Metazoa Species 0.000 claims abstract 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 252
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 227
-1 -NR10R11 Chemical group 0.000 claims description 200
125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 139
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 123
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 82
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 77
239000001257 hydrogen Substances 0.000 claims description 70
229910052739 hydrogen Inorganic materials 0.000 claims description 70
125000001424 substituent group Chemical group 0.000 claims description 52
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 51
238000000034 method Methods 0.000 claims description 47
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 47
238000006243 chemical reaction Methods 0.000 claims description 45
125000000217 alkyl group Chemical group 0.000 claims description 42
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 38
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 34
229910020008 S(O) Inorganic materials 0.000 claims description 30
229910052736 halogen Inorganic materials 0.000 claims description 27
150000002367 halogens Chemical class 0.000 claims description 27
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 25
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 24
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 24
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 23
239000004305 biphenyl Substances 0.000 claims description 22
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 20
125000001153 fluoro group Chemical group F* 0.000 claims description 20
229910052757 nitrogen Inorganic materials 0.000 claims description 17
GTKIGDZXPDCIKR-UHFFFAOYSA-N 2-phenylbenzamide Chemical compound NC(=O)C1=CC=CC=C1C1=CC=CC=C1 GTKIGDZXPDCIKR-UHFFFAOYSA-N 0.000 claims description 16
125000005010 perfluoroalkyl group Chemical group 0.000 claims description 16
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 15
125000006239 protecting group Chemical group 0.000 claims description 15
LEPWUMPXISBPIB-UHFFFAOYSA-N 4-phenylbutanamide Chemical compound NC(=O)CCCC1=CC=CC=C1 LEPWUMPXISBPIB-UHFFFAOYSA-N 0.000 claims description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
229910052760 oxygen Inorganic materials 0.000 claims description 14
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 13
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
125000000753 cycloalkyl group Chemical group 0.000 claims description 12
125000002883 imidazolyl group Chemical group 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 11
125000001041 indolyl group Chemical group 0.000 claims description 10
150000003536 tetrazoles Chemical class 0.000 claims description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
125000004432 carbon atom Chemical group C* 0.000 claims description 8
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 6
101100277337 Arabidopsis thaliana DDM1 gene Proteins 0.000 claims description 6
239000000095 Growth Hormone-Releasing Hormone Substances 0.000 claims description 6
101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 6
101710142969 Somatoliberin Proteins 0.000 claims description 6
239000000048 adrenergic agonist Substances 0.000 claims description 6
125000003342 alkenyl group Chemical group 0.000 claims description 6
101150113676 chr1 gene Proteins 0.000 claims description 6
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
208000008589 Obesity Diseases 0.000 claims description 5
208000001132 Osteoporosis Diseases 0.000 claims description 5
125000000304 alkynyl group Chemical group 0.000 claims description 5
125000001624 naphthyl group Chemical group 0.000 claims description 5
235000020824 obesity Nutrition 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
102200001405 rs377584435 Human genes 0.000 claims description 5
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 claims description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
125000004423 acyloxy group Chemical group 0.000 claims description 4
125000000623 heterocyclic group Chemical group 0.000 claims description 4
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
229940122361 Bisphosphonate Drugs 0.000 claims description 3
102000003982 Parathyroid hormone Human genes 0.000 claims description 3
108090000445 Parathyroid hormone Proteins 0.000 claims description 3
150000004663 bisphosphonates Chemical class 0.000 claims description 3
239000000199 parathyroid hormone Substances 0.000 claims description 3
229960001319 parathyroid hormone Drugs 0.000 claims description 3
NWQWNCILOXTTHF-HLCSKTDOSA-N (2s)-6-amino-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-aminopropanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](N)C)C(=O)N[C@H](CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CNC=N1 NWQWNCILOXTTHF-HLCSKTDOSA-N 0.000 claims description 2
WZHKXNSOCOQYQX-FUAFALNISA-N (2s)-6-amino-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]amino]hexanamide Chemical compound C([C@H](N)C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CN=CN1 WZHKXNSOCOQYQX-FUAFALNISA-N 0.000 claims description 2
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 2
BFTXPZVZWWRFDW-HHHXNRCGSA-N 2-[4-[[[(2r)-2-[(2-amino-2-methylpropanoyl)amino]-3-(1h-indol-3-yl)propanoyl]amino]methyl]phenyl]-n-ethylbenzamide Chemical compound CCNC(=O)C1=CC=CC=C1C(C=C1)=CC=C1CNC(=O)[C@H](NC(=O)C(C)(C)N)CC1=CNC2=CC=CC=C12 BFTXPZVZWWRFDW-HHHXNRCGSA-N 0.000 claims description 2
RWBOKYLGFVWAJS-AREMUKBSSA-N 2-[4-[[[(2r)-2-[(2-amino-2-methylpropanoyl)amino]-3-[(2,6-difluorophenyl)methoxy]propanoyl]amino]methyl]phenyl]-n-ethylbenzamide Chemical compound CCNC(=O)C1=CC=CC=C1C(C=C1)=CC=C1CNC(=O)[C@H](NC(=O)C(C)(C)N)COCC1=C(F)C=CC=C1F RWBOKYLGFVWAJS-AREMUKBSSA-N 0.000 claims description 2
XWYGHYCAGUOOQP-AREMUKBSSA-N 2-[4-[[[(2r)-2-[(2-amino-2-methylpropanoyl)amino]-3-phenylmethoxypropanoyl]amino]methyl]phenyl]-n-ethylbenzamide Chemical compound CCNC(=O)C1=CC=CC=C1C(C=C1)=CC=C1CNC(=O)[C@H](NC(=O)C(C)(C)N)COCC1=CC=CC=C1 XWYGHYCAGUOOQP-AREMUKBSSA-N 0.000 claims description 2
DHSSDEDRBUKTQY-UHFFFAOYSA-N 6-prop-2-enyl-4,5,7,8-tetrahydrothiazolo[4,5-d]azepin-2-amine Chemical compound C1CN(CC=C)CCC2=C1N=C(N)S2 DHSSDEDRBUKTQY-UHFFFAOYSA-N 0.000 claims description 2
108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 2
102000048143 Insulin-Like Growth Factor II Human genes 0.000 claims description 2
108090001117 Insulin-Like Growth Factor II Proteins 0.000 claims description 2
PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 claims description 2
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
229920001774 Perfluoroether Polymers 0.000 claims description 2
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
108010083553 alanyl-histidyl-(2-naphthyl)alanyl-tryptophyl-phenylalanyl-lysinamide Proteins 0.000 claims description 2
RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 2
JYZIHLWOWKMNNX-UHFFFAOYSA-N benzimidazole Chemical compound C1=C[CH]C2=NC=NC2=C1 JYZIHLWOWKMNNX-UHFFFAOYSA-N 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
108010015153 growth hormone releasing hexapeptide Proteins 0.000 claims description 2
239000003324 growth hormone secretagogue Substances 0.000 claims description 2
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims description 2
229930192474 thiophene Natural products 0.000 claims description 2
150000003852 triazoles Chemical class 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 21
JURWPUACOPQKGW-UHFFFAOYSA-N 5-phenylpentanamide Chemical compound NC(=O)CCCCC1=CC=CC=C1 JURWPUACOPQKGW-UHFFFAOYSA-N 0.000 claims 12
241001334141 Rugopharynx alpha Species 0.000 claims 3
102000038461 Growth Hormone-Releasing Hormone Human genes 0.000 claims 2
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims 1
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NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/25—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/29—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/30—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/04—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms
- C07C275/20—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
- C07C275/24—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
- 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
- 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
- C07D209/18—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
- C07D209/20—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 substituted additionally by nitrogen atoms, e.g. tryptophane
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Epidemiology (AREA)
Endocrinology (AREA)
Immunology (AREA)
Gastroenterology & Hepatology (AREA)
Zoology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Diabetes (AREA)
General Chemical & Material Sciences (AREA)
Molecular Biology (AREA)
Obesity (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Hematology (AREA)
Genetics & Genomics (AREA)
Child & Adolescent Psychology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

CA002147503A 1992-11-06 1993-10-29 Analogues de dipeptides substitues stimulant la liberation de l'hormone de croissance Abandoned CA2147503A1 (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US973,142		1978-12-26
US97314292A	1992-11-06	1992-11-06

Publications (1)

Publication Number	Publication Date
CA2147503A1 true CA2147503A1 (fr)	1994-05-26

Family

ID=25520551

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002147503A Abandoned CA2147503A1 (fr)	1992-11-06	1993-10-29	Analogues de dipeptides substitues stimulant la liberation de l'hormone de croissance

Country Status (5)

Country	Link
EP (1)	EP0669830A4 (fr)
JP (1)	JPH08503213A (fr)
AU (1)	AU676525B2 (fr)
CA (1)	CA2147503A1 (fr)
WO (1)	WO1994011012A1 (fr)

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Publication number	Priority date	Publication date	Assignee	Title
WO1995014666A1 (fr) *	1993-11-24	1995-06-01	Merck & Co., Inc.	Composes contenant un groupe indolyle et leur utilisation pour favoriser la liberation d'hormones(s) de croissance
US5798337A (en) *	1994-11-16	1998-08-25	Genentech, Inc.	Low molecular weight peptidomimetic growth hormone secretagogues
US20020111461A1 (en)	1999-05-21	2002-08-15	Todd C. Somers	Low molecular weight peptidomimetic growth hormone secretagogues
JPH08325248A (ja) *	1995-05-26	1996-12-10	Chugoku Kayaku Kk	テトラゾール類の新規な合成試薬及びそれを用いたテトラゾール類の製造方法
EP0828754B1 (fr) *	1995-05-29	2005-02-02	Pfizer Inc.	Dipeptides favorisant la secretion de l'hormone de croissance
JP3798024B2 (ja)	1995-12-13	2006-07-19	メルクエンドカンパニーインコーポレーテッド	成長ホルモン分泌促進物質レセプターアッセイ
US6531314B1 (en)	1996-12-10	2003-03-11	Merck & Co., Inc.	Growth hormone secretagogue receptor family
GB2308362A (en) *	1995-12-19	1997-06-25	Lilly Industries Ltd	Pharmaceutical indole derivatives
WO1998058947A1 (fr)	1997-06-25	1998-12-30	Pfizer Inc.	Derives dipeptides secretagogues de l'hormone de croissance
UA53716C2 (uk)	1997-06-25	2003-02-17	Пфайзер Продактс Інк.	Тартратна сіль заміщеного дипептиду, спосіб її одержання, проміжні сполуки та спосіб їх одержання, фармацевтична композиція (варіанти), спосіб підвищення рівнів ендогенного гормону росту та спосіб лікування або профілактики захворювань (варіанти)
UA64751C2 (uk)	1997-06-25	2004-03-15	Пфайзер Продактс Інк.	Спосіб лікування інсулінової толерантності речовинами, які посилюють секрецію гормону росту (варіанти) та фармацевтична композиція (варіанти)
US6682908B1 (en)	1998-07-10	2004-01-27	Merck & Co., Inc.	Mouse growth hormone secretagogue receptor
WO2000002919A1 (fr)	1998-07-13	2000-01-20	Merck & Co., Inc.	Recepteurs et acides nucleiques en rapport avec un secretagogue d'hormone de croissance
CA2340095A1 (fr)	1998-08-10	2000-02-24	Merck & Co., Inc.	Recepteur de secretagogue d'hormone de croissance canine
US6358951B1 (en)	1998-08-21	2002-03-19	Pfizer Inc.	Growth hormone secretagogues
CA2362290A1 (fr)	1999-02-18	2000-08-24	Kaken Pharmaceutical Co., Ltd.	Nouveaux derives amide secretagogues de l'hormone de croissance
ATE446758T1 (de)	2000-05-31	2009-11-15	Pfizer Prod Inc	Verwendung von wachstumshormonsekretagoga zur förderung der beweglichkeit des verdauungstrakts
DE602004014321D1 (de) *	2003-01-16	2008-07-24	Teva Pharma	Neue synthese von irbesartan
US7476653B2 (en)	2003-06-18	2009-01-13	Tranzyme Pharma, Inc.	Macrocyclic modulators of the ghrelin receptor
UA87854C2 (en)	2004-06-07	2009-08-25	Мерк Энд Ко., Инк.	N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators
CU23558A1 (es)	2006-02-28	2010-07-20	Ct Ingenieria Genetica Biotech	Compuestos análogos a los secretagogos peptidicos de la hormona de crecimiento
EP1931648A2 (fr) *	2006-08-29	2008-06-18	Teva Pharmaceutical Industries Ltd.	Procede pour la synthese du 5-phenyl-1-trityl-1h-tetrazole
EP2644618B1 (fr)	2007-02-09	2016-08-17	Ocera Therapeutics, Inc.	Intermédaires dans la synthese de modulateurs macrocycliques du récepteur de la ghréline
WO2008134828A2 (fr)	2007-05-04	2008-11-13	Katholieke Universiteit Leuven	Protection contre la dégénérescence tissulaire
WO2013190520A2 (fr)	2012-06-22	2013-12-27	The General Hospital Corporation	Agents de libération de gh dans le traitement d'une sténose vasculaire et d'états associés
US9119832B2 (en)	2014-02-05	2015-09-01	The Regents Of The University Of California	Methods of treating mild brain injury
BR112016027778A2 (pt)	2014-05-30	2017-08-15	Pfizer	Usos de derivados de carbonitrila, sua combinação e sua composição farmacêutica
US20170121385A1 (en)	2015-10-28	2017-05-04	Oxeia Biopharmaceuticals, Inc.	Methods of treating neurodegenerative conditions
CN106748860A (zh) *	2016-11-22	2017-05-31	浙江工业大学	钯/碳催化苯环上特定官能团邻位芳基化的方法
JP7217749B2 (ja) *	2017-12-27	2023-02-03	フラマソシエタペルアチオニ	ペプチド誘導体およびその治療活性
WO2021143762A1 (fr) *	2020-01-17	2021-07-22	Shengke Pharmaceuticals (Jiangsu) Ltd.	Nouveaux composés en tant qu'inhibiteurs de pcsk9
WO2023275715A1 (fr)	2021-06-30	2023-01-05	Pfizer Inc.	Métabolites de modulateurs sélectifs du récepteur des androgènes

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE68922602T2 (de) *	1988-01-28	1995-12-07	Polygen Holding Corp	Polypeptide mit hormonwachstumsbefreiender wirkung.
US5206235A (en) *	1991-03-20	1993-04-27	Merck & Co., Inc.	Benzo-fused lactams that promote the release of growth hormone
US5583130A (en) *	1992-09-25	1996-12-10	Merck & Co., Inc.	Benzo-fused lactams promote release of growth hormone
US5317017A (en) *	1992-09-30	1994-05-31	Merck & Co., Inc.	N-biphenyl-3-amido substituted benzolactams stimulate growth hormone release

1993
- 1993-10-29 WO PCT/US1993/010551 patent/WO1994011012A1/fr not_active Application Discontinuation
- 1993-10-29 JP JP6512178A patent/JPH08503213A/ja active Pending
- 1993-10-29 EP EP94900505A patent/EP0669830A4/fr not_active Withdrawn
- 1993-10-29 AU AU55469/94A patent/AU676525B2/en not_active Ceased
- 1993-10-29 CA CA002147503A patent/CA2147503A1/fr not_active Abandoned

Also Published As

Publication number	Publication date
EP0669830A1 (fr)	1995-09-06
WO1994011012A1 (fr)	1994-05-26
AU5546994A (en)	1994-06-08
AU676525B2 (en)	1997-03-13
JPH08503213A (ja)	1996-04-09
EP0669830A4 (fr)	1997-02-26

Legal Events

Date	Code	Title	Description
2001-10-29	FZDE	Dead

Publication	Publication Date	Title
AU676525B2 (en)	1997-03-13	Substituted dipeptide analogs promote release of growth hormone
AU676501B2 (en)	1997-03-13	Benzo-fused lactams promote release of growth hormone
AU683081B2 (en)	1997-10-30	Benzo-fused lactams promote release of growth hormone
WO1995009633A1 (fr)	1995-04-13	Lactanes benzo-fusionnes promoteurs de la liberation de l'hormone de croissance
US5606054A (en)	1997-02-25	Heterocyclic-fused lactams promote release of growth hormone
EP0659179B1 (fr)	2001-11-21	Lactames a benzofusion stimulant la liberation de l'hormone de croissance
US5726307A (en)	1998-03-10	Benzo-fused lactams promote release of growth hormone
AU676210B2 (en)	1997-03-06	Benzo-fused lactams promote release of growth hormone
WO1995003289A1 (fr)	1995-02-02	Lactames benzofuses promoteurs de la secretion de l'hormone de croissance
JPH08814B2 (ja)	1996-01-10	成長ホルモン放出促進新規ベンゾ縮合ラクタム類
US5726319A (en)	1998-03-10	Biphenyl substituted dipeptide analogs promote release of growth hormone
CA2174235A1 (fr)	1995-05-11	Macrocycles benzo-condenses stimulant la liberation de l'hormone de croissance
WO1995016675A1 (fr)	1995-06-22	Lactames benzo condenses favorisant la liberation de l'hormone de croissance