DK166586C - Spirocycliske aminosyrederivater samt deres fysiologisk acceptable salte, fremgangsmaade til deres fremstilling, deres anvendelse som laegemiddel samt laegemidler indeholdende dem - Google Patents

Spirocycliske aminosyrederivater samt deres fysiologisk acceptable salte, fremgangsmaade til deres fremstilling, deres anvendelse som laegemiddel samt laegemidler indeholdende dem Download PDF

Info

Publication number: DK166586C
Authority: DK; Denmark
Prior art keywords: formula; compound; hydrogen; amino acid; optionally
Prior art date: 1983-01-12

Application number

DK011984A

Other languages

Danish (da)

English (en)

Other versions

DK11984A (da

DK11984D0 (da

DK166586B (da

Inventor

Rainer Henning

Hansjoerg Urbach

Volker Teetz

Reinhard Becker

Original Assignee

Hoechst Ag

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.)

1983-01-12

Filing date

1984-01-11

Publication date

1993-11-08

1984-01-11 Application filed by Hoechst Ag filed Critical Hoechst Ag

1984-01-11 Publication of DK11984D0 publication Critical patent/DK11984D0/da

1984-07-13 Publication of DK11984A publication Critical patent/DK11984A/da

1993-06-14 Publication of DK166586B publication Critical patent/DK166586B/da

1993-11-08 Application granted granted Critical

1993-11-08 Publication of DK166586C publication Critical patent/DK166586C/da

Links

238000000034 method Methods 0.000 title claims abstract description 26
150000003862 amino acid derivatives Chemical class 0.000 title claims abstract description 16
238000002360 preparation method Methods 0.000 title claims abstract description 10
150000003839 salts Chemical class 0.000 title claims description 18
239000003814 drug Substances 0.000 title claims 6
239000001257 hydrogen Substances 0.000 claims abstract description 32
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 32
125000000217 alkyl group Chemical group 0.000 claims abstract description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
150000002431 hydrogen Chemical class 0.000 claims abstract description 12
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
239000001301 oxygen Substances 0.000 claims abstract description 6
229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
150000001875 compounds Chemical class 0.000 claims description 106
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
125000004432 carbon atom Chemical group C* 0.000 claims description 7
230000002378 acidificating effect Effects 0.000 claims description 6
150000002148 esters Chemical class 0.000 claims description 6
239000002934 diuretic Substances 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
239000002262 Schiff base Substances 0.000 claims description 3
150000004753 Schiff bases Chemical class 0.000 claims description 3
230000001882 diuretic effect Effects 0.000 claims description 3
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 3
125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims description 2
229940079593 drug Drugs 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 1
-1 nitro, amino Chemical group 0.000 abstract description 22
150000001413 amino acids Chemical class 0.000 abstract description 7
229910052736 halogen Inorganic materials 0.000 abstract description 3
150000002367 halogens Chemical group 0.000 abstract description 3
239000003795 chemical substances by application Substances 0.000 abstract description 2
125000003342 alkenyl group Chemical group 0.000 abstract 3
125000003710 aryl alkyl group Chemical group 0.000 abstract 3
125000003118 aryl group Chemical group 0.000 abstract 3
125000003545 alkoxy group Chemical group 0.000 abstract 2
125000000753 cycloalkyl group Chemical group 0.000 abstract 2
125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 2
125000004442 acylamino group Chemical group 0.000 abstract 1
125000003282 alkyl amino group Chemical group 0.000 abstract 1
150000001370 alpha-amino acid derivatives Chemical class 0.000 abstract 1
235000008206 alpha-amino acids Nutrition 0.000 abstract 1
235000001014 amino acid Nutrition 0.000 abstract 1
125000006196 aroyl alkyl group Chemical group 0.000 abstract 1
150000005840 aryl radicals Chemical class 0.000 abstract 1
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 abstract 1
125000000392 cycloalkenyl group Chemical group 0.000 abstract 1
125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract 1
125000004663 dialkyl amino group Chemical group 0.000 abstract 1
239000000543 intermediate Substances 0.000 abstract 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
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239000000243 solution Substances 0.000 description 22
238000005160 1H NMR spectroscopy Methods 0.000 description 21
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 20
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238000005481 NMR spectroscopy Methods 0.000 description 18
239000002904 solvent Substances 0.000 description 17
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239000000741 silica gel Substances 0.000 description 15
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239000000203 mixture Substances 0.000 description 12
239000002253 acid Substances 0.000 description 11
YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
238000003756 stirring Methods 0.000 description 8
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
239000002585 base Substances 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 6
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
238000001819 mass spectrum Methods 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
238000007792 addition Methods 0.000 description 5
125000004122 cyclic group Chemical group 0.000 description 5
239000003921 oil Substances 0.000 description 5
235000019198 oils Nutrition 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 4
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 4
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 4
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UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
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239000012043 crude product Substances 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
239000012071 phase Substances 0.000 description 4
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238000004566 IR spectroscopy Methods 0.000 description 3
RKOTXQYWCBGZLP-UHFFFAOYSA-N N-[(2,4-difluorophenyl)methyl]-2-ethyl-9-hydroxy-3-methoxy-1,8-dioxospiro[3H-pyrido[1,2-a]pyrazine-4,3'-oxolane]-7-carboxamide Chemical compound CCN1C(OC)C2(CCOC2)N2C=C(C(=O)NCC3=C(F)C=C(F)C=C3)C(=O)C(O)=C2C1=O RKOTXQYWCBGZLP-UHFFFAOYSA-N 0.000 description 3
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KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000001816 cooling Methods 0.000 description 3
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
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HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
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238000006683 Mannich reaction Methods 0.000 description 2
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125000002619 bicyclic group Chemical group 0.000 description 2
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239000003638 chemical reducing agent Substances 0.000 description 2
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238000000605 extraction Methods 0.000 description 2
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WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
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FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
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206010020772 Hypertension Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
238000006845 Michael addition reaction Methods 0.000 description 1
238000006957 Michael reaction Methods 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
241000700159 Rattus Species 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
235000019486 Sunflower oil Nutrition 0.000 description 1
BHXMDLROFMLUJY-UHFFFAOYSA-N [2-(1,3-dioxolan-2-yl)-1-methyl-2-bicyclo[2.2.2]octanyl]methanamine Chemical compound NCC1(C2(CCC(C1)CC2)C)C1OCCO1 BHXMDLROFMLUJY-UHFFFAOYSA-N 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
238000010306 acid treatment Methods 0.000 description 1
239000000654 additive Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
125000000539 amino acid group Chemical group 0.000 description 1
229910021529 ammonia Inorganic materials 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
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
239000010775 animal oil Substances 0.000 description 1
239000002220 antihypertensive agent Substances 0.000 description 1
229940030600 antihypertensive agent Drugs 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
SIFLTZSFMCAHNE-UHFFFAOYSA-N benzyl spiro[bicyclo[2.2.1]heptane-3,4'-pyrrolidine]-2'-carboxylate;hydrochloride Chemical compound Cl.C1C2(C3CCC(C3)C2)CNC1C(=O)OCC1=CC=CC=C1 SIFLTZSFMCAHNE-UHFFFAOYSA-N 0.000 description 1
GAHKEUUHTHVKEA-UHFFFAOYSA-N bicyclo(2.2.1)heptane-2-carbonitrile Chemical compound C1CC2C(C#N)CC1C2 GAHKEUUHTHVKEA-UHFFFAOYSA-N 0.000 description 1
FNWILXGSWPUHIE-UHFFFAOYSA-N bicyclo[2.2.2]octane-3-carbonitrile Chemical compound C1CC2C(C#N)CC1CC2 FNWILXGSWPUHIE-UHFFFAOYSA-N 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
230000004531 blood pressure lowering effect Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
229920001429 chelating resin Polymers 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
238000006482 condensation reaction Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
229940030606 diuretics Drugs 0.000 description 1
239000008298 dragée Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 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
ACXLBHHUHSJENU-UHFFFAOYSA-N ethyl 4-oxo-4-phenylbut-2-enoate Chemical compound CCOC(=O)C=CC(=O)C1=CC=CC=C1 ACXLBHHUHSJENU-UHFFFAOYSA-N 0.000 description 1
DBPFRRFGLYGEJI-UHFFFAOYSA-N ethyl glyoxylate Chemical compound CCOC(=O)C=O DBPFRRFGLYGEJI-UHFFFAOYSA-N 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
AHNJTQYTRPXLLG-UHFFFAOYSA-N lithium;diethylazanide Chemical compound [Li+].CC[N-]CC AHNJTQYTRPXLLG-UHFFFAOYSA-N 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
235000014380 magnesium carbonate Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
239000000178 monomer Substances 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000002504 physiological saline solution 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
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
229910000343 potassium bisulfate Inorganic materials 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 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
239000010970 precious metal Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000000047 product Substances 0.000 description 1
ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical compound CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Chemical group CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
230000007017 scission Effects 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 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
239000011780 sodium chloride Substances 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
DPRWTIWKLYJXRM-UHFFFAOYSA-N spiro[bicyclo[2.2.1]heptane-3,4'-pyrrolidine]-2'-carbonitrile Chemical compound C1NC(C#N)CC21C(C1)CCC1C2 DPRWTIWKLYJXRM-UHFFFAOYSA-N 0.000 description 1
DFZCJECNCPSDKZ-UHFFFAOYSA-N spiro[bicyclo[2.2.1]heptane-3,4'-pyrrolidine]-2'-carboxylic acid Chemical compound C1NC(C(=O)O)CC21C(C1)CCC1C2 DFZCJECNCPSDKZ-UHFFFAOYSA-N 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000002600 sunflower oil Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000563 toxic property Toxicity 0.000 description 1
230000001960 triggered effect Effects 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
230000007306 turnover Effects 0.000 description 1
230000000304 vasodilatating effect Effects 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1

Classifications

- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- 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
- C07D209/56—Ring systems containing three or more rings
- C07D209/96—Spiro-condensed ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/28—Radicals substituted by nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/30—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
- 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)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Genetics & Genomics (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Pyrrole Compounds (AREA)

DK011984A 1983-01-12 1984-01-11 Spirocycliske aminosyrederivater samt deres fysiologisk acceptable salte, fremgangsmaade til deres fremstilling, deres anvendelse som laegemiddel samt laegemidler indeholdende dem DK166586C (da)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19833300774 DE3300774A1 (de)	1983-01-12	1983-01-12	Neue spirocyclische aminosaeuren, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie neue spirocyclische aminosaeuren als zwischenprodukte und verfahren zu deren herstellung
DE3300774		1983-01-12

Publications (4)

Publication Number	Publication Date
DK11984D0 DK11984D0 (da)	1984-01-11
DK11984A DK11984A (da)	1984-07-13
DK166586B DK166586B (da)	1993-06-14
DK166586C true DK166586C (da)	1993-11-08

Family

ID=6188100

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK011984A DK166586C (da)	1983-01-12	1984-01-11	Spirocycliske aminosyrederivater samt deres fysiologisk acceptable salte, fremgangsmaade til deres fremstilling, deres anvendelse som laegemiddel samt laegemidler indeholdende dem

Country Status (13)

Country	Link
US (1)	US4620012A (ja)
EP (1)	EP0116276B1 (ja)
JP (1)	JPH0759590B2 (ja)
KR (1)	KR910003185B1 (ja)
AT (1)	ATE39931T1 (ja)
AU (1)	AU575308B2 (ja)
DE (2)	DE3300774A1 (ja)
DK (1)	DK166586C (ja)
ES (2)	ES528761A0 (ja)
GR (1)	GR79158B (ja)
IE (1)	IE56544B1 (ja)
PT (1)	PT77943B (ja)
ZA (1)	ZA84213B (ja)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
CA1341296C (en) *	1981-12-29	2001-09-25	Hansjorg Urbach	2-azabicycloalkane-3-carboxylic acid derivatives, processes for their preparation, agents containing these compounds and their use
US5175306A (en) *	1983-01-31	1992-12-29	Hoechst Aktiengesellschaft	Process for the resolution of racemates of optically active bicyclic imino-α-carboxylic esters
DE3333455A1 (de) *	1983-09-16	1985-04-11	Hoechst Ag, 6230 Frankfurt	Verfahren zur herstellung n-alkylierter dipeptide und deren estern
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
WO1986007064A1 (fr) *	1985-05-22	1986-12-04	Takeda Chemical Industries, Ltd.	Derives de piperidine
US5231080A (en) *	1985-10-15	1993-07-27	Hoechst Aktiengesellschaft	Method for the treatment of atherosclerosis, thrombosis, and peripheral vessel disease
DE3610391A1 (de) *	1986-03-27	1987-10-08	Hoechst Ag	Verbindungen mit nootroper wirkung, diese enthaltende mittel und deren verwendung bei der behandlung und prophylaxe cognitiver dysfunktionen
US5231084A (en) *	1986-03-27	1993-07-27	Hoechst Aktiengesellschaft	Compounds having a cognition adjuvant action, agents containing them, and the use thereof for the treatment and prophylaxis of cognitive dysfuncitons
CS277405B6 (en) *	1986-06-12	1993-03-17	Vyzk Ustav Farm Biochem Sp	Peptides with 1-amino-1-cycloalkane carboxylic acid
DE3633496A1 (de) *	1986-10-02	1988-04-14	Hoechst Ag	Kombination von angiotensin-converting-enzyme-hemmern mit calciumantagonisten sowie deren verwendung in arzneimitteln
DE3639879A1 (de) *	1986-11-21	1988-06-01	Hoechst Ag	Verfahren zur herstellung von mono-, bi- und tricyclischen aminosaeuren, zwischenprodukte dieses verfahrens sowie ein verfahren zu deren herstellung
DE3722007A1 (de) *	1987-07-03	1989-01-12	Hoechst Ag	Verfahren zur herstellung bicyclischer aminocarbonsaeuren, zwischenprodukte dieses verfahrens und deren verwendung
HU904967D0 (en) *	1988-04-22	1991-01-28	Hoechst Ag	Process for producing new azabicyclo(3.3.o)octane-3-carboxylic acid-octylesther derivatives
CN1131855C (zh) *	1997-12-16	2003-12-24	沃尼尔·朗伯公司	1－取代－1－氨基甲基－环烷衍生物(=加巴喷丁类似物)、其制备及其在治疗神经病方面的用途
CA2521364A1 (en) *	2003-04-15	2004-10-28	Warner-Lambert Company Llc	[c]-fused bicyclic proline derivatives and their use for treating arthritic conditions
WO2004092132A1 (en) *	2003-04-15	2004-10-28	Warner-Lambert Company Llc	[b]-fused bicyclic proline derivatives and their use for treating arthritic conditions
CN113372324A (zh) *	2021-06-18	2021-09-10	山东大学苏州研究院	一种通过碘化锂催化合成螺环类化合物的方法

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL58849A (en) *	1978-12-11	1983-03-31	Merck & Co Inc	Carboxyalkyl dipeptides and derivatives thereof,their preparation and pharmaceutical compositions containing them
ATE20469T1 (de) *	1980-10-23	1986-07-15	Schering Corp	Carboxyalkyl-dipeptide, verfahren zu ihrer herstellung und diese enthaltende arzneimittel.
DE3211397A1 (de) *	1982-03-27	1983-11-10	Hoechst Ag, 6230 Frankfurt	Spiro (4.(3+n))-2-aza-3-carbonsaeure-derivate, verfahren zu ihrer herstellung, diese enthaltende mittel und ihre verwendung

1983
- 1983-01-12 DE DE19833300774 patent/DE3300774A1/de not_active Withdrawn
1984
- 1984-01-09 DE DE8484100130T patent/DE3476067D1/de not_active Expired
- 1984-01-09 AT AT84100130T patent/ATE39931T1/de not_active IP Right Cessation
- 1984-01-09 EP EP84100130A patent/EP0116276B1/de not_active Expired
- 1984-01-10 GR GR73477A patent/GR79158B/el unknown
- 1984-01-10 KR KR1019840000070A patent/KR910003185B1/ko not_active Expired
- 1984-01-10 US US06/569,758 patent/US4620012A/en not_active Expired - Lifetime
- 1984-01-10 ES ES528761A patent/ES528761A0/es active Granted
- 1984-01-11 IE IE48/84A patent/IE56544B1/en not_active IP Right Cessation
- 1984-01-11 PT PT77943A patent/PT77943B/pt not_active IP Right Cessation
- 1984-01-11 ZA ZA84213A patent/ZA84213B/xx unknown
- 1984-01-11 DK DK011984A patent/DK166586C/da active
- 1984-01-11 JP JP59002113A patent/JPH0759590B2/ja not_active Expired - Lifetime
- 1984-01-11 AU AU23229/84A patent/AU575308B2/en not_active Ceased
- 1984-03-05 ES ES530290A patent/ES8500905A1/es not_active Expired

Also Published As

Publication number	Publication date
KR840007585A (ko)	1984-12-08
ES8406880A1 (es)	1984-09-01
US4620012A (en)	1986-10-28
ES530290A0 (es)	1984-11-01
DE3300774A1 (de)	1984-07-12
PT77943A (de)	1984-02-01
ES8500905A1 (es)	1984-11-01
EP0116276A2 (de)	1984-08-22
ATE39931T1 (de)	1989-01-15
AU575308B2 (en)	1988-07-28
JPS59134765A (ja)	1984-08-02
GR79158B (ja)	1984-10-02
DK11984A (da)	1984-07-13
IE56544B1 (en)	1991-08-28
DK11984D0 (da)	1984-01-11
DE3476067D1 (en)	1989-02-16
DK166586B (da)	1993-06-14
IE840048L (en)	1984-07-12
ZA84213B (en)	1984-08-29
PT77943B (de)	1986-05-30
AU2322984A (en)	1984-07-19
JPH0759590B2 (ja)	1995-06-28
ES528761A0 (es)	1984-09-01
KR910003185B1 (ko)	1991-05-22
EP0116276B1 (de)	1989-01-11
EP0116276A3 (en)	1985-11-27

Publication	Publication Date	Title
DK166586C (da)	1993-11-08	Spirocycliske aminosyrederivater samt deres fysiologisk acceptable salte, fremgangsmaade til deres fremstilling, deres anvendelse som laegemiddel samt laegemidler indeholdende dem
DK171256B1 (da)	1996-08-12	Analogifremgangsmåde til fremstilling af derivater af bicycliske aminosyrer eller fysiologisk acceptable salte deraf
FI81087B (fi)	1990-05-31	Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 1-acyl-2-azabicyklo/3.3.0/-3-karboxylsyror.
US4933361A (en)	1990-06-12	Derivatives of bicyclic aminoacids agents containing these compounds and their use
US4714708A (en)	1987-12-22	Derivatives of cis, endo-2-azabicyclo[5.3.0]decane-3-carboxylic acid, and their use for treating hypertension
KR910000255B1 (ko)	1991-01-23	트리사이클릭아미노산 유도체의 제조방법
HU193876B (en)	1987-12-28	Process for preparing cycloalkane /c/ pyrrol-1-carboxypeptides and pharmaceutics comprising the same
JPS5929686A (ja)	1984-02-16	２−アザビシクロ〔２．２．２〕オクタン−３−カルボン酸の新規な誘導体およびそれらの製造法
JPH0559105B2 (ja)	1993-08-30
KR910001438B1 (ko)	1991-03-07	광학적 활성 비시클릭 이미노-α-카복실산 에스테르 라세미체의 분할방법
EP0113880A2 (de)	1984-07-25	Neue 2-Azabicyclo(2.2.1)heptan-Derivate, Verfahren zu ihrer Herstellung, diese enthaltende Mittel und deren Verwendung sowie 2-Azabicyclo(2.2.1)heptan-Derivate als Zwischenprodukte und Verfahren zu deren Herstellung
US4920144A (en)	1990-04-24	Derivatives of bicyclic amino acids, agents containing them and their use as hypotensives