DK169382B1 - Analogifremgangsmåde til fremstilling af alanylderivater af isoquinolinderivater - Google Patents
Analogifremgangsmåde til fremstilling af alanylderivater af isoquinolinderivater Download PDFInfo
- Publication number
- DK169382B1 DK169382B1 DK383581A DK383581A DK169382B1 DK 169382 B1 DK169382 B1 DK 169382B1 DK 383581 A DK383581 A DK 383581A DK 383581 A DK383581 A DK 383581A DK 169382 B1 DK169382 B1 DK 169382B1
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- DK
- Denmark
- Prior art keywords
- formula
- compound
- prepared
- carboxylic acid
- carboxy
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 20
- 230000008569 process Effects 0.000 title claims description 9
- 125000001980 alanyl group Chemical group 0.000 title claims description 5
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 47
- -1 mercapto, hydroxy, amino, carboxy, phenyl Chemical group 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 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 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 125000004185 ester group Chemical group 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000005046 dihydronaphthyl group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Chemical group 0.000 claims description 2
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- 230000002829 reductive effect Effects 0.000 claims description 2
- 150000003457 sulfones Chemical class 0.000 claims description 2
- 150000003462 sulfoxides Chemical class 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 3
- QROMPSIBAFZLBD-XQDFYDKTSA-N 1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound N([C@@H](C)C(=O)C1C2=CC=CC=C2CC(N1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 QROMPSIBAFZLBD-XQDFYDKTSA-N 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-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
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 238000009833 condensation Methods 0.000 description 6
- 230000005494 condensation Effects 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 230000036772 blood pressure Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- BWKMGYQJPOAASG-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound C1=CC=C2CNC(C(=O)O)CC2=C1 BWKMGYQJPOAASG-UHFFFAOYSA-N 0.000 description 3
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Inorganic materials [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 3
- 230000004531 blood pressure lowering effect Effects 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 150000002367 halogens Chemical group 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 238000006268 reductive amination reaction Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- KRSUDBIZXKOKGA-LBPRGKRZSA-N tert-butyl (3s)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate Chemical compound C1=CC=C2CN[C@H](C(=O)OC(C)(C)C)CC2=C1 KRSUDBIZXKOKGA-LBPRGKRZSA-N 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- LMRHIUYUOMQZDE-YMVQICGQSA-N 1-[(2s)-2-[(1-carboxy-2-phenylsulfanylethyl)amino]propanoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound N([C@@H](C)C(=O)C1C2=CC=CC=C2CC(N1)C(O)=O)C(C(O)=O)CSC1=CC=CC=C1 LMRHIUYUOMQZDE-YMVQICGQSA-N 0.000 description 2
- PBGCEAJPMCOPNE-NBGSKHHUSA-N 1-[(2s)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound N([C@@H](C)C(=O)C1C2=CC=CC=C2CC(N1)C(O)=O)C(C(O)=O)CCC1=CC=CC=C1 PBGCEAJPMCOPNE-NBGSKHHUSA-N 0.000 description 2
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- 239000002262 Schiff base Substances 0.000 description 2
- 150000004753 Schiff bases Chemical class 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000003862 amino acid derivatives Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 239000007859 condensation product Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 2
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 2
- 239000008057 potassium phosphate buffer Substances 0.000 description 2
- 229940107700 pyruvic acid Drugs 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- GAWAYYRQGQZKCR-UWTATZPHSA-N (2r)-2-chloropropanoic acid Chemical compound C[C@@H](Cl)C(O)=O GAWAYYRQGQZKCR-UWTATZPHSA-N 0.000 description 1
- CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 1
- OXFGRWIKQDSSLY-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinolin-2-ium-1-carboxylate Chemical compound C1=CC=C2C(C(=O)O)NCCC2=C1 OXFGRWIKQDSSLY-UHFFFAOYSA-N 0.000 description 1
- JYLIQZNPLZNKNU-XQDFYDKTSA-N 1-[(2S)-2-aminopropanoyl]-2-(1-ethoxy-1-oxo-4-phenylbutan-2-yl)-3,4-dihydro-1H-isoquinoline-3-carboxylic acid Chemical compound OC(=O)C1CC2=CC=CC=C2C(C(=O)[C@H](C)N)N1C(C(=O)OCC)CCC1=CC=CC=C1 JYLIQZNPLZNKNU-XQDFYDKTSA-N 0.000 description 1
- SVSWTMDXBBRFKD-LCOVJITISA-N 1-[(2S)-2-aminopropanoyl]-2-[1-ethoxy-1-oxo-4-(phenylmethoxycarbonylamino)butan-2-yl]-3,4-dihydro-1H-isoquinoline-3-carboxylic acid Chemical compound C(=O)(OCC)C(CCNC(=O)OCC1=CC=CC=C1)N1C(C2=CC=CC=C2CC1C(=O)O)C([C@@H](N)C)=O SVSWTMDXBBRFKD-LCOVJITISA-N 0.000 description 1
- ZNGKQGXJBGWXGJ-ARTQYDKTSA-N 1-[(2s)-2-aminopropanoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)[C@@H](N)C)NC(C(O)=O)CC2=C1 ZNGKQGXJBGWXGJ-ARTQYDKTSA-N 0.000 description 1
- CQYBNXGHMBNGCG-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydro-1h-indol-1-ium-2-carboxylate Chemical class C1CCCC2NC(C(=O)O)CC21 CQYBNXGHMBNGCG-UHFFFAOYSA-N 0.000 description 1
- WUZOUJIQTKVXPF-JBAGZYDGSA-N 2-(2-amino-1-carboxypropyl)-1-[(2s)-2-aminopropanoyl]-3,4-dihydro-1h-isoquinoline-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)[C@H](C)N)N(C(C(N)C)C(O)=O)C(C(O)=O)CC2=C1 WUZOUJIQTKVXPF-JBAGZYDGSA-N 0.000 description 1
- LIRWCOQICAXRJT-UHFFFAOYSA-N 2-(2-oxopropanoyl)-3,4-dihydro-1h-isoquinoline-3-carboxylic acid Chemical compound C1=CC=C2CC(C(O)=O)N(C(=O)C(=O)C)CC2=C1 LIRWCOQICAXRJT-UHFFFAOYSA-N 0.000 description 1
- IHIXKLZIBVDPLV-DIOLFPMVSA-N 2-(5-amino-1-carboxypentyl)-1-[(2s)-2-aminopropanoyl]-3,4-dihydro-1h-isoquinoline-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)[C@@H](N)C)N(C(CCCCN)C(O)=O)C(C(O)=O)CC2=C1 IHIXKLZIBVDPLV-DIOLFPMVSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- MGDZOQNTLSBULE-LCOVJITISA-N 2-[1-[(2S)-2-aminopropanoyl]-3-[(2-methylpropan-2-yl)oxycarbonyl]-3,4-dihydro-1H-isoquinolin-2-yl]-4-phenylbutanoic acid Chemical compound C(C)(C)(C)OC(=O)C1N(C(C2=CC=CC=C2C1)C([C@@H](N)C)=O)C(CCC1=CC=CC=C1)C(=O)O MGDZOQNTLSBULE-LCOVJITISA-N 0.000 description 1
- IFVNXXLNXBKHOB-XQXASTNHSA-N 2-[5-amino-1-carboxy-6-[(2-methylpropan-2-yl)oxy]-6-oxohexyl]-1-[(2s)-2-aminopropanoyl]-3,4-dihydro-1h-isoquinoline-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)[C@@H](N)C)N(C(CCCC(N)C(=O)OC(C)(C)C)C(O)=O)C(C(O)=O)CC2=C1 IFVNXXLNXBKHOB-XQXASTNHSA-N 0.000 description 1
- SIBIINRIEGKULC-XQDFYDKTSA-N 2-[[(2s)-1-[3-[(2-methylpropan-2-yl)oxycarbonyl]-1,2,3,4-tetrahydroisoquinolin-1-yl]-1-oxopropan-2-yl]amino]-3-phenylsulfanylpropanoic acid Chemical compound N([C@@H](C)C(=O)C1C2=CC=CC=C2CC(N1)C(=O)OC(C)(C)C)C(C(O)=O)CSC1=CC=CC=C1 SIBIINRIEGKULC-XQDFYDKTSA-N 0.000 description 1
- XYUBQWNJDIAEES-UHFFFAOYSA-N 2-azaniumyl-3-phenylsulfanylpropanoate Chemical compound OC(=O)C(N)CSC1=CC=CC=C1 XYUBQWNJDIAEES-UHFFFAOYSA-N 0.000 description 1
- YWVQGUBCAUFBCP-UHFFFAOYSA-N 2-phenylmethoxycarbonyl-3,4-dihydro-1h-isoquinoline-3-carboxylic acid Chemical compound OC(=O)C1CC2=CC=CC=C2CN1C(=O)OCC1=CC=CC=C1 YWVQGUBCAUFBCP-UHFFFAOYSA-N 0.000 description 1
- ZSYMMQSHFBERCN-UHFFFAOYSA-N 3,3-diaminobutanoic acid Chemical compound CC(N)(N)CC(O)=O ZSYMMQSHFBERCN-UHFFFAOYSA-N 0.000 description 1
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 1
- 102000005862 Angiotensin II Human genes 0.000 description 1
- 101800000734 Angiotensin-1 Proteins 0.000 description 1
- 102400000344 Angiotensin-1 Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- CRBCPOILZDEEGD-DIOLFPMVSA-N C(=O)(OCC)C(CCN)N1C(C2=CC=CC=C2CC1C(=O)O)C([C@@H](N)C)=O Chemical compound C(=O)(OCC)C(CCN)N1C(C2=CC=CC=C2CC1C(=O)O)C([C@@H](N)C)=O CRBCPOILZDEEGD-DIOLFPMVSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 241001122767 Theaceae Species 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 229940124572 antihypotensive agent Drugs 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- JYJCXXFNEVFGGO-QGLTVNCISA-N butyl 1-[(2s)-2-aminopropanoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylate Chemical compound C1=CC=C2C(C(=O)[C@H](C)N)NC(C(=O)OCCCC)CC2=C1 JYJCXXFNEVFGGO-QGLTVNCISA-N 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- STPXIOGYOLJXMZ-UHFFFAOYSA-N ethyl 2-oxo-4-phenylbutanoate Chemical compound CCOC(=O)C(=O)CCC1=CC=CC=C1 STPXIOGYOLJXMZ-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000003977 halocarboxylic acids Chemical class 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- QNRXNRGSOJZINA-UHFFFAOYSA-N indoline-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)CC2=C1 QNRXNRGSOJZINA-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- TYRGLVWXHJRKMT-QMMMGPOBSA-N n-benzyloxycarbonyl-l-serine-betalactone Chemical compound OC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 TYRGLVWXHJRKMT-QMMMGPOBSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- CQYBNXGHMBNGCG-RNJXMRFFSA-N octahydroindole-2-carboxylic acid Chemical compound C1CCC[C@H]2N[C@H](C(=O)O)C[C@@H]21 CQYBNXGHMBNGCG-RNJXMRFFSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- KVCGISUBCHHTDD-UHFFFAOYSA-M sodium;4-methylbenzenesulfonate Chemical compound [Na+].CC1=CC=C(S([O-])(=O)=O)C=C1 KVCGISUBCHHTDD-UHFFFAOYSA-M 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000005622 tetraalkylammonium hydroxides Chemical class 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000563 toxic property Toxicity 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—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
- 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
- C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
- C07K5/0222—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2 with the first amino acid being heterocyclic, e.g. Pro, Trp
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Furan Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19803032709 DE3032709A1 (de) | 1980-08-30 | 1980-08-30 | Aminosaeurederivate, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung |
| DE3032709 | 1980-08-30 | ||
| DE3118191 | 1981-05-08 | ||
| DE19813118191 DE3118191A1 (de) | 1981-05-08 | 1981-05-08 | Aminosaeurederivate, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK383581A DK383581A (da) | 1982-03-01 |
| DK169382B1 true DK169382B1 (da) | 1994-10-17 |
Family
ID=25787513
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK383581A DK169382B1 (da) | 1980-08-30 | 1981-08-28 | Analogifremgangsmåde til fremstilling af alanylderivater af isoquinolinderivater |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US5158959A (fr) |
| EP (2) | EP0046953B1 (fr) |
| JP (3) | JPS5777672A (fr) |
| KR (3) | KR850001269B1 (fr) |
| AR (2) | AR240949A1 (fr) |
| AU (2) | AU599151B2 (fr) |
| CS (1) | CS409491A3 (fr) |
| DE (2) | DE3177311D1 (fr) |
| DK (1) | DK169382B1 (fr) |
| ES (3) | ES504955A0 (fr) |
| FI (1) | FI90072C (fr) |
| GR (1) | GR75331B (fr) |
| HU (1) | HU189531B (fr) |
| IE (1) | IE67438B1 (fr) |
| NO (1) | NO812933L (fr) |
| NZ (1) | NZ198195A (fr) |
| PH (1) | PH16812A (fr) |
| PT (1) | PT73584B (fr) |
Families Citing this family (90)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2503155A2 (fr) * | 1980-10-02 | 1982-10-08 | Science Union & Cie | Nouveaux imino diacides substitues, leurs procedes de preparation et leur emploi comme inhibiteur d'enzyme |
| DE3177311D1 (de) * | 1980-08-30 | 1994-06-09 | Hoechst Ag | Aminosäurederivate, Verfahren zu ihrer Herstellung, diese enthaltende Mittel und deren Verwendung. |
| US4344949A (en) * | 1980-10-03 | 1982-08-17 | Warner-Lambert Company | Substituted acyl derivatives of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids |
| ZA817261B (en) * | 1980-10-23 | 1982-09-29 | Schering Corp | Carboxyalkyl dipeptides,processes for their production and pharmaceutical compositions containing them |
| DE19575012I2 (de) * | 1980-10-23 | 2002-01-24 | Schering Corp | Carboxyalkyl-Dipeptide Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel |
| US4479963A (en) * | 1981-02-17 | 1984-10-30 | Ciba-Geigy Corporation | 1-Carboxyalkanoylindoline-2-carboxylic acids |
| US4532342A (en) * | 1981-02-20 | 1985-07-30 | Warner-Lambert Company | N-substituted amino acids as intermediates in the preparation of acyl derivatives of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids |
| IN156096B (fr) * | 1981-03-19 | 1985-05-11 | Usv Pharma Corp | |
| JPS5833430A (ja) * | 1981-03-25 | 1983-02-26 | Showa Denko Kk | 吹込成形金型 |
| EP0065301A1 (fr) * | 1981-05-18 | 1982-11-24 | Merck & Co. Inc. | Dérivés des acides isoquinoléine-carboxyliques, leur procédé de préparation et compositions pharmaceutiques qui les contiennent |
| SU1327787A3 (ru) * | 1981-11-05 | 1987-07-30 | Хехст Аг (Фирма) | Способ получени цис,эндо-2-азабицикло-/3,3,0/-октан-3-карбоновых кислот или их кислотно-аддитивных солей |
| DE3226768A1 (de) * | 1981-11-05 | 1983-05-26 | Hoechst Ag, 6230 Frankfurt | Derivate der cis, endo-2-azabicyclo-(3.3.0)-octan-3-carbonsaeure, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung |
| EP0079522B1 (fr) * | 1981-11-09 | 1986-05-07 | Merck & Co. Inc. | Agents antihypertendus N-carboxyméthyl(amidino)-lysyl-prolines |
| GR78413B (fr) * | 1981-12-29 | 1984-09-27 | Hoechst Ag | |
| DE3227055A1 (de) * | 1982-07-20 | 1984-01-26 | Hoechst Ag, 6230 Frankfurt | Neue derivate der 2-aza-bicyclo(2.2.2)octan-3-carbonsaeure, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie 2-aza-bicyclo(2.2.2)octan-3-carbonsaeure als zwischenstufe und verfahren zu deren herstellung |
| US4500713A (en) * | 1982-09-23 | 1985-02-19 | Usv Pharmaceutical Corporation | Therapeutic dipeptides |
| DE3302125A1 (de) * | 1983-01-22 | 1984-07-26 | Boehringer Ingelheim KG, 6507 Ingelheim | Aminosaeure-derivate, verfahren zu ihrer herstellung und verwendung |
| US5175306A (en) * | 1983-01-31 | 1992-12-29 | Hoechst Aktiengesellschaft | Process for the resolution of racemates of optically active bicyclic imino-α-carboxylic esters |
| DE3303344A1 (de) | 1983-02-02 | 1984-08-02 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung von n-alkylierten aminosaeuren und deren estern |
| DK156484A (da) * | 1983-03-16 | 1984-09-17 | Usv Pharma Corp | Aminosyrederivater |
| DE3315464A1 (de) * | 1983-04-28 | 1984-10-31 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung von n-alkylierten dipeptiden und deren estern |
| FR2546886B2 (fr) * | 1983-06-06 | 1986-05-16 | Adir | Derives d'acides isoindoledicarboxyliques, leur preparation et compositions pharmaceutiques les contenant |
| DE3333455A1 (de) * | 1983-09-16 | 1985-04-11 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung n-alkylierter dipeptide und deren estern |
| DE3333454A1 (de) * | 1983-09-16 | 1985-04-11 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung von n-alkylierten dipeptiden und deren estern |
| DE3408923A1 (de) * | 1984-03-12 | 1985-09-26 | Hoechst Ag, 6230 Frankfurt | Carboxyalkyldipeptidderivate, verfahren zu deren herstellung, diese enthaltende mittel und deren verwendung |
| DE3410732A1 (de) * | 1984-03-23 | 1985-09-26 | Hoechst Ag, 6230 Frankfurt | Methode zur behandlung des glaukoms |
| US5684016A (en) * | 1984-04-12 | 1997-11-04 | Hoechst Aktiengesellschaft | Method of treating cardiac insufficiency |
| DE3413710A1 (de) * | 1984-04-12 | 1985-10-24 | Hoechst Ag, 6230 Frankfurt | Verfahren zur behandlung der herzinsuffizienz |
| DE3431541A1 (de) * | 1984-08-28 | 1986-03-06 | Hoechst Ag, 6230 Frankfurt | Cis,endo-2-azabicycloalkan-3-carbonsaeure-derivate, verfahren zu deren herstellung, deren verwendung sowie zwischenprodukte bei deren herstellung |
| GB8422165D0 (en) * | 1984-09-01 | 1984-10-03 | Wellcome Found | Compounds |
| EP0187037A3 (fr) * | 1984-12-21 | 1988-03-23 | Takeda Chemical Industries, Ltd. | Dérivés de pipéridine, leur production et emploi |
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-
1981
- 1981-08-22 DE DE3177311T patent/DE3177311D1/de not_active Expired - Lifetime
- 1981-08-22 EP EP81106535A patent/EP0046953B1/fr not_active Expired
- 1981-08-22 DE DE8181106535T patent/DE3177130D1/de not_active Expired - Lifetime
- 1981-08-22 EP EP88102408A patent/EP0278530A3/fr not_active Ceased
- 1981-08-25 ES ES504955A patent/ES504955A0/es active Granted
- 1981-08-27 FI FI812652A patent/FI90072C/fi not_active IP Right Cessation
- 1981-08-27 PT PT73584A patent/PT73584B/pt unknown
- 1981-08-27 HU HU812478A patent/HU189531B/hu unknown
- 1981-08-28 DK DK383581A patent/DK169382B1/da active
- 1981-08-28 NO NO812933A patent/NO812933L/no unknown
- 1981-08-28 JP JP56134401A patent/JPS5777672A/ja active Pending
- 1981-08-28 AR AR286576A patent/AR240949A1/es active
- 1981-08-28 KR KR1019810003193A patent/KR850001269B1/ko active
- 1981-08-28 GR GR65886A patent/GR75331B/el unknown
- 1981-08-28 IE IE198681A patent/IE67438B1/en not_active IP Right Cessation
- 1981-08-28 PH PH26117A patent/PH16812A/en unknown
- 1981-08-28 NZ NZ198195A patent/NZ198195A/en unknown
- 1981-09-18 ES ES505604A patent/ES8301214A1/es not_active Expired
- 1981-09-18 ES ES505605A patent/ES8301215A1/es not_active Expired
-
1982
- 1982-06-29 AR AR28982682A patent/AR240702A1/es active
-
1983
- 1983-12-27 US US06/565,900 patent/US5158959A/en not_active Expired - Lifetime
-
1984
- 1984-09-27 KR KR1019840005957A patent/KR850001270B1/ko not_active IP Right Cessation
- 1984-09-27 KR KR1019840006028A patent/KR850001288B1/ko not_active IP Right Cessation
-
1987
- 1987-10-01 AU AU79284/87A patent/AU599151B2/en not_active Expired
-
1988
- 1988-08-25 JP JP63209625A patent/JPH0678355B2/ja not_active Expired - Lifetime
-
1989
- 1989-06-20 AU AU36625/89A patent/AU627741B2/en not_active Expired
-
1991
- 1991-03-18 JP JP3077208A patent/JPH07121955B2/ja not_active Expired - Lifetime
- 1991-12-27 CS CS914094A patent/CS409491A3/cs unknown
-
1994
- 1994-03-09 US US08/208,443 patent/US5401766A/en not_active Expired - Lifetime
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