NO312298B1 - Analogifremgangsmåte for fremstilling av terapeutisk aktive indolderivater - Google Patents
Analogifremgangsmåte for fremstilling av terapeutisk aktive indolderivater Download PDFInfo
- Publication number
- NO312298B1 NO312298B1 NO19930709A NO930709A NO312298B1 NO 312298 B1 NO312298 B1 NO 312298B1 NO 19930709 A NO19930709 A NO 19930709A NO 930709 A NO930709 A NO 930709A NO 312298 B1 NO312298 B1 NO 312298B1
- Authority
- NO
- Norway
- Prior art keywords
- dec
- methyl
- tricyclo
- amino
- ester
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 48
- 238000002360 preparation method Methods 0.000 title claims description 17
- 230000008569 process Effects 0.000 title claims description 8
- 229940054051 antipsychotic indole derivative Drugs 0.000 title 1
- 150000002475 indoles Chemical class 0.000 title 1
- -1 1-adamantyl Chemical group 0.000 claims description 228
- 150000001875 compounds Chemical class 0.000 claims description 167
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 75
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 67
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 66
- 229910052739 hydrogen Inorganic materials 0.000 claims description 65
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 55
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims description 55
- 150000002148 esters Chemical class 0.000 claims description 44
- 150000001408 amides Chemical class 0.000 claims description 40
- 125000003670 adamantan-2-yl group Chemical group [H]C1([H])C(C2([H])[H])([H])C([H])([H])C3([H])C([*])([H])C1([H])C([H])([H])C2([H])C3([H])[H] 0.000 claims description 31
- 150000001412 amines Chemical class 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 23
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 12
- 239000004471 Glycine Substances 0.000 claims description 9
- LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 claims description 9
- QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical compound OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000007858 starting material Substances 0.000 claims description 7
- OBSIQMZKFXFYLV-MRVPVSSYSA-N (2r)-2-amino-3-phenylpropanamide Chemical compound NC(=O)[C@H](N)CC1=CC=CC=C1 OBSIQMZKFXFYLV-MRVPVSSYSA-N 0.000 claims description 6
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 claims description 6
- OBSIQMZKFXFYLV-QMMMGPOBSA-N L-phenylalanine amide Chemical compound NC(=O)[C@@H](N)CC1=CC=CC=C1 OBSIQMZKFXFYLV-QMMMGPOBSA-N 0.000 claims description 6
- 150000002431 hydrogen Chemical group 0.000 claims description 6
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 claims description 6
- YXXKMTIGKAVJTA-UHFFFAOYSA-N ac1l3htk Chemical group C1C(C2)CC3[CH]C1CC2C3 YXXKMTIGKAVJTA-UHFFFAOYSA-N 0.000 claims description 5
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 5
- PJZAZUXDFXNADM-SODSUQDMSA-N 2-[(e)-1,3-benzodioxol-5-ylmethylideneamino]-1-hydroxyguanidine;4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.ONC(=N)N\N=C\C1=CC=C2OCOC2=C1 PJZAZUXDFXNADM-SODSUQDMSA-N 0.000 claims description 4
- VAJVDSVGBWFCLW-UHFFFAOYSA-N 3-Phenyl-1-propanol Chemical compound OCCCC1=CC=CC=C1 VAJVDSVGBWFCLW-UHFFFAOYSA-N 0.000 claims description 4
- PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 claims description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 4
- 150000001371 alpha-amino acids Chemical class 0.000 claims description 4
- 235000008206 alpha-amino acids Nutrition 0.000 claims description 4
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 claims description 3
- 229930182832 D-phenylalanine Natural products 0.000 claims description 3
- 229910052786 argon Inorganic materials 0.000 claims description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
- GYTGOLDQGRPDNF-VNKDHWASSA-N (2e,4e)-hepta-2,4-dienoic acid Chemical compound CC\C=C\C=C\C(O)=O GYTGOLDQGRPDNF-VNKDHWASSA-N 0.000 claims description 2
- GYTGOLDQGRPDNF-UHFFFAOYSA-N (E,E)-2,4-Heptadienoic acid Natural products CCC=CC=CC(O)=O GYTGOLDQGRPDNF-UHFFFAOYSA-N 0.000 claims description 2
- ROMNEYAQUBNRLR-UHFFFAOYSA-N 2-(4-hydroxybiphenyl-3-yl)-4-methyl-1h-isoindole-1,3(2h)-dione Chemical compound O=C1C=2C(C)=CC=CC=2C(=O)N1C(C(=CC=1)O)=CC=1C1=CC=CC=C1 ROMNEYAQUBNRLR-UHFFFAOYSA-N 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 2
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 384
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 314
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 239
- 239000000243 solution Substances 0.000 description 194
- 235000019439 ethyl acetate Nutrition 0.000 description 143
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 124
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 124
- 238000006243 chemical reaction Methods 0.000 description 114
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 109
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 90
- 239000000203 mixture Substances 0.000 description 85
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 84
- 239000003480 eluent Substances 0.000 description 76
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- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 60
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
- 239000010408 film Substances 0.000 description 57
- 229910001868 water Inorganic materials 0.000 description 57
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 55
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 54
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 52
- 238000004458 analytical method Methods 0.000 description 52
- 229910052799 carbon Inorganic materials 0.000 description 50
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
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- 229910002027 silica gel Inorganic materials 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 40
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 39
- 239000006260 foam Substances 0.000 description 36
- 238000003756 stirring Methods 0.000 description 35
- 230000015572 biosynthetic process Effects 0.000 description 32
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- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 31
- 238000003786 synthesis reaction Methods 0.000 description 31
- 239000000460 chlorine Substances 0.000 description 30
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 29
- 239000002253 acid Substances 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- 239000000706 filtrate Substances 0.000 description 26
- 229910052757 nitrogen Inorganic materials 0.000 description 26
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 24
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 24
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- 101800001982 Cholecystokinin Proteins 0.000 description 22
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- 239000003921 oil Substances 0.000 description 21
- 235000019198 oils Nutrition 0.000 description 21
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 20
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- STVVMTBJNDTZBF-VIFPVBQESA-N L-phenylalaninol Chemical compound OC[C@@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-VIFPVBQESA-N 0.000 description 18
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 18
- 239000012071 phase Substances 0.000 description 17
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 17
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- 239000012044 organic layer Substances 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
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- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 8
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- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 8
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Classifications
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- 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
- C07K5/08—Tripeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/595—Gastrins; Cholecystokinins [CCK]
-
- 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
- A61P1/04—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
-
- 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
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- 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
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06156—Dipeptides with the first amino acid being heterocyclic and Trp-amino acid; 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Endocrinology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US57662890A | 1990-08-31 | 1990-08-31 | |
US72665591A | 1991-07-12 | 1991-07-12 | |
PCT/US1991/006180 WO1992004045A1 (fr) | 1990-08-31 | 1991-08-29 | Nouveaux antagonistes de cholecystokinine, preparation et utilisation therapeutique de ces composes |
Publications (3)
Publication Number | Publication Date |
---|---|
NO930709D0 NO930709D0 (no) | 1993-02-26 |
NO930709L NO930709L (no) | 1993-04-15 |
NO312298B1 true NO312298B1 (no) | 2002-04-22 |
Family
ID=27077012
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19930709A NO312298B1 (no) | 1990-08-31 | 1993-02-26 | Analogifremgangsmåte for fremstilling av terapeutisk aktive indolderivater |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP0547178A4 (fr) |
JP (1) | JPH06502627A (fr) |
KR (1) | KR100222634B1 (fr) |
CA (1) | CA2088195A1 (fr) |
IE (1) | IE67290B1 (fr) |
NO (1) | NO312298B1 (fr) |
NZ (1) | NZ239595A (fr) |
PT (1) | PT98842B (fr) |
WO (1) | WO1992004045A1 (fr) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5217957A (en) * | 1991-08-20 | 1993-06-08 | Warner-Lambert Company | Cholecystokinin antagonists useful for treating depression |
US5380872A (en) * | 1992-07-14 | 1995-01-10 | Glaxo Inc. | Modulators of cholecystokinin |
WO1994018229A1 (fr) * | 1993-02-03 | 1994-08-18 | Fisons Corporation | Derives de 1,2,4 triazone et leur utilisation en therapeutique |
GB9304500D0 (en) * | 1993-03-05 | 1993-04-21 | Glaxo Spa | Heterocyclic compounds |
JP2001500850A (ja) | 1996-08-22 | 2001-01-23 | ワーナー―ランバート・コンパニー | 非―ペプチドボンベシン受容体アンタゴニスト |
US6645968B2 (en) | 1999-08-03 | 2003-11-11 | Abbott Laboratories | Potassium channel openers |
US6846836B2 (en) | 2003-04-18 | 2005-01-25 | Bristol-Myers Squibb Company | N-substituted phenylurea inhibitors of mitochondrial F1F0 ATP hydrolase |
WO2005077344A2 (fr) | 2003-08-29 | 2005-08-25 | The Brigham And Women's Hospital, Inc. | Inhibiteurs de la necrose cellulaire |
US8604244B2 (en) | 2010-07-02 | 2013-12-10 | Reviva Pharmaceuticals, Inc. | Compositions, synthesis, and methods of using cycloalkylmethylamine derivatives |
EP2066329B1 (fr) | 2006-09-15 | 2017-09-06 | Reviva Pharmaceuticals, Inc. | Synthèse, utilisation et compositions de cyclobutylméthylamines |
EP3000468A1 (fr) | 2008-12-23 | 2016-03-30 | President and Fellows of Harvard College | Inhibiteurs à petite molécule de la nécroptose |
GB0919194D0 (en) | 2009-11-02 | 2009-12-16 | Lytix Biopharma As | Compounds |
US20160024098A1 (en) | 2013-03-15 | 2016-01-28 | President And Fellows Of Harvard College | Hybrid necroptosis inhibitors |
WO2016094846A1 (fr) | 2014-12-11 | 2016-06-16 | President And Fellows Of Harvard College | Inhibiteurs de nécrose cellulaire et procédés associés |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4757151A (en) * | 1985-11-14 | 1988-07-12 | Warner-Lambert Company | 2-substituted-[2-substituted-amino]-N-arylalkyl-3-[indol-3-yl] |
CA1291031C (fr) * | 1985-12-23 | 1991-10-22 | Nikolaas C.J. De Jaeger | Methode pour la detection de liants specifiques et des substances liables par ceux-ci |
US4814463A (en) * | 1985-12-31 | 1989-03-21 | Biomeasure, Inc. | CCK antagonists |
FR2606963B1 (fr) * | 1986-11-14 | 1989-01-13 | Cit Alcatel | Boitier de repeteur sous-marin |
WO1989010355A1 (fr) * | 1988-04-05 | 1989-11-02 | Abbott Laboratories | Derives de tryptophan utilises comme antagonistes cck |
NZ234264A (en) * | 1989-06-29 | 1993-05-26 | Warner Lambert Co | N-substituted cycloalkyl and polycycloalkyl alpha-substituted trp-phe- and phenethylamine derivatives, and pharmaceutical compositions |
US5244915A (en) * | 1990-08-31 | 1993-09-14 | Warner-Lambert Company | Amico acid derivatives cyclized at the c-terminal |
-
1991
- 1991-08-29 WO PCT/US1991/006180 patent/WO1992004045A1/fr not_active Application Discontinuation
- 1991-08-29 KR KR1019930700601A patent/KR100222634B1/ko not_active IP Right Cessation
- 1991-08-29 NZ NZ239595A patent/NZ239595A/en unknown
- 1991-08-29 CA CA002088195A patent/CA2088195A1/fr not_active Abandoned
- 1991-08-29 JP JP3517185A patent/JPH06502627A/ja active Pending
- 1991-08-29 EP EP19910918880 patent/EP0547178A4/en not_active Withdrawn
- 1991-08-30 PT PT98842A patent/PT98842B/pt not_active IP Right Cessation
- 1991-08-30 IE IE307791A patent/IE67290B1/en not_active IP Right Cessation
-
1993
- 1993-02-26 NO NO19930709A patent/NO312298B1/no not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
NO930709D0 (no) | 1993-02-26 |
CA2088195A1 (fr) | 1992-03-01 |
EP0547178A4 (en) | 1994-07-06 |
NZ239595A (en) | 1994-06-27 |
AU651390B2 (en) | 1994-07-21 |
JPH06502627A (ja) | 1994-03-24 |
WO1992004045A1 (fr) | 1992-03-19 |
KR930703349A (ko) | 1993-11-29 |
PT98842A (pt) | 1992-08-31 |
KR100222634B1 (ko) | 1999-10-01 |
IE67290B1 (en) | 1996-03-20 |
PT98842B (pt) | 1999-01-29 |
IE913077A1 (en) | 1992-03-11 |
EP0547178A1 (fr) | 1993-06-23 |
NO930709L (no) | 1993-04-15 |
AU8749291A (en) | 1992-03-30 |
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MM1K | Lapsed by not paying the annual fees |