SK278095B6 - Peptide derivatives, method of its production and their use - Google Patents

Peptide derivatives, method of its production and their use Download PDF

Info

Publication number: SK278095B6
Authority: SK; Slovakia
Prior art keywords: mmol; trifluoro; product; solution; methanol
Prior art date: 1985-01-22

Application number

SK395-86A

Other languages

English (en)

Slovak (sk)

Inventor

Scott H Bergeson

Philip D Edwards

John A Schwartz

Andrew Shaw

Mark Morris Stein

Diane A Trainor

Richard A Wildonger

Donald J Wolanin

Original Assignee

Ici America Inc

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.)

1985-01-22

Filing date

1986-01-20

Publication date

1995-12-06

1985-01-22 Priority claimed from GB858501523A external-priority patent/GB8501523D0/en

1985-01-22 Priority claimed from GB858501524A external-priority patent/GB8501524D0/en

1985-01-22 Priority claimed from GB858501522A external-priority patent/GB8501522D0/en

1986-01-20 Application filed by Ici America Inc filed Critical Ici America Inc

1995-12-06 Publication of SK278095B6 publication Critical patent/SK278095B6/sk

Links

238000000034 method Methods 0.000 title claims abstract description 140
108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 17
238000004519 manufacturing process Methods 0.000 title claims description 4
150000001875 compounds Chemical class 0.000 claims abstract description 246
238000006243 chemical reaction Methods 0.000 claims abstract description 53
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 31
150000003839 salts Chemical class 0.000 claims abstract description 17
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 4
-1 phenylsulfonylamino Chemical group 0.000 claims description 480
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 408
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 90
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 53
125000004432 carbon atom Chemical group C* 0.000 claims description 50
239000002904 solvent Substances 0.000 claims description 41
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 36
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 36
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 20
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 18
125000000217 alkyl group Chemical group 0.000 claims description 17
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
150000003254 radicals Chemical class 0.000 claims description 14
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 11
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 10
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 8
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 8
239000004480 active ingredient Substances 0.000 claims description 7
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 6
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 6
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
125000005476 oxopyrrolidinyl group Chemical group 0.000 claims description 4
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
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229910052736 halogen Inorganic materials 0.000 claims description 2
125000002757 morpholinyl group Chemical group 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
229940124530 sulfonamide Drugs 0.000 claims description 2
150000003456 sulfonamides Chemical class 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 1
150000002367 halogens Chemical class 0.000 claims 1
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231100000252 nontoxic Toxicity 0.000 claims 1
230000003000 nontoxic effect Effects 0.000 claims 1
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239000001257 hydrogen Substances 0.000 abstract description 11
230000003647 oxidation Effects 0.000 abstract description 6
238000007254 oxidation reaction Methods 0.000 abstract description 6
230000004048 modification Effects 0.000 abstract description 2
238000012986 modification Methods 0.000 abstract description 2
125000004122 cyclic group Chemical group 0.000 abstract 1
239000008177 pharmaceutical agent Substances 0.000 abstract 1
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239000000047 product Substances 0.000 description 290
239000000243 solution Substances 0.000 description 279
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 228
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 223
238000003818 flash chromatography Methods 0.000 description 149
239000000203 mixture Substances 0.000 description 144
238000004809 thin layer chromatography Methods 0.000 description 135
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 131
229910052757 nitrogen Inorganic materials 0.000 description 128
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 126
238000004128 high performance liquid chromatography Methods 0.000 description 115
229910002091 carbon monoxide Inorganic materials 0.000 description 114
239000000741 silica gel Substances 0.000 description 107
229910002027 silica gel Inorganic materials 0.000 description 107
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 101
239000011541 reaction mixture Substances 0.000 description 101
229910052799 carbon Inorganic materials 0.000 description 96
238000000746 purification Methods 0.000 description 86
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 81
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 81
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IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 80
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 80
239000000463 material Substances 0.000 description 78
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 75
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 74
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 67
229910052938 sodium sulfate Inorganic materials 0.000 description 66
235000011152 sodium sulphate Nutrition 0.000 description 66
239000012267 brine Substances 0.000 description 63
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 63
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 60
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 60
239000012043 crude product Substances 0.000 description 60
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 56
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 49
239000007787 solid Substances 0.000 description 49
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
238000004458 analytical method Methods 0.000 description 46
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 45
238000001914 filtration Methods 0.000 description 44
238000003756 stirring Methods 0.000 description 44
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 40
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 40
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238000010828 elution Methods 0.000 description 34
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 31
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 30
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229920006395 saturated elastomer Polymers 0.000 description 28
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DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 27
229910000030 sodium bicarbonate Inorganic materials 0.000 description 26
235000017557 sodium bicarbonate Nutrition 0.000 description 26
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
239000003480 eluent Substances 0.000 description 24
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125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 21
101000851058 Homo sapiens Neutrophil elastase Proteins 0.000 description 20
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102100033174 Neutrophil elastase Human genes 0.000 description 19
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239000000843 powder Substances 0.000 description 19
239000011780 sodium chloride Substances 0.000 description 19
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NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 11
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238000000926 separation method Methods 0.000 description 9
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238000002360 preparation method Methods 0.000 description 5
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238000011067 equilibration Methods 0.000 description 1
239000006167 equilibration buffer Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
HXVGHXDQGUPUKY-UHFFFAOYSA-N ethyl 2-isocyanatobenzoate Chemical compound CCOC(=O)C1=CC=CC=C1N=C=O HXVGHXDQGUPUKY-UHFFFAOYSA-N 0.000 description 1
BFFNUXPWJPYBJG-UHFFFAOYSA-N ethyl 4-(4-carbamoylphenoxy)butanoate Chemical compound CCOC(=O)CCCOC1=CC=C(C(N)=O)C=C1 BFFNUXPWJPYBJG-UHFFFAOYSA-N 0.000 description 1
XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 1
BHYVHYPBRYOMGC-UHFFFAOYSA-N ethyl 4-formylbenzoate Chemical compound CCOC(=O)C1=CC=C(C=O)C=C1 BHYVHYPBRYOMGC-UHFFFAOYSA-N 0.000 description 1
MLOJHUCMCKBDLV-UHFFFAOYSA-N ethyl 4-isothiocyanatobenzoate Chemical compound CCOC(=O)C1=CC=C(N=C=S)C=C1 MLOJHUCMCKBDLV-UHFFFAOYSA-N 0.000 description 1
235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
239000011888 foil Substances 0.000 description 1
210000000540 fraction c Anatomy 0.000 description 1
238000004508 fractional distillation Methods 0.000 description 1
239000000295 fuel oil Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000000499 gel Substances 0.000 description 1
229960002989 glutamic acid Drugs 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
235000004554 glutamine Nutrition 0.000 description 1
230000005484 gravity Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
238000011141 high resolution liquid chromatography Methods 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 description 1
230000000415 inactivating effect Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
230000010354 integration Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000001282 iso-butane Substances 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
229960000310 isoleucine Drugs 0.000 description 1
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical class OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
235000018977 lysine Nutrition 0.000 description 1
239000012528 membrane Substances 0.000 description 1
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
PCZIAHHJBQNSLD-UHFFFAOYSA-N methanol;oxolane;toluene Chemical compound OC.C1CCOC1.CC1=CC=CC=C1 PCZIAHHJBQNSLD-UHFFFAOYSA-N 0.000 description 1
KDXZREBVGAGZHS-UHFFFAOYSA-M methohexital sodium Chemical compound [Na+].CCC#CC(C)C1(CC=C)C(=O)N=C([O-])N(C)C1=O KDXZREBVGAGZHS-UHFFFAOYSA-M 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
HQEIPVHJHZTMDP-JEDNCBNOSA-N methyl (2s)-pyrrolidine-2-carboxylate;hydrochloride Chemical compound Cl.COC(=O)[C@@H]1CCCN1 HQEIPVHJHZTMDP-JEDNCBNOSA-N 0.000 description 1
ZOYZUQWERCKOQE-UHFFFAOYSA-N methyl 12-(2-carboxyoxy-5-nitrophenyl)dodecanoate Chemical compound COC(=O)CCCCCCCCCCCC1=C(C=CC(=C1)[N+](=O)[O-])OC(=O)O ZOYZUQWERCKOQE-UHFFFAOYSA-N 0.000 description 1
WVYBBOXJKXXXOY-UHFFFAOYSA-N methyl 12-hydroxydodecanoate Chemical compound COC(=O)CCCCCCCCCCCO WVYBBOXJKXXXOY-UHFFFAOYSA-N 0.000 description 1
CSTFJAKYMFPIJV-UHFFFAOYSA-N methyl 2-(4-carbamoylphenoxy)acetate Chemical compound COC(=O)COC1=CC=C(C(N)=O)C=C1 CSTFJAKYMFPIJV-UHFFFAOYSA-N 0.000 description 1
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
QQVNCBCBFNWLJX-KCHLEUMXSA-N n-[(2s)-1-[[(2s)-1-[[(2s)-5-(diaminomethylideneamino)-1-(4-nitroanilino)-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]benzamide Chemical compound C([C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)C=1C=CC=CC=1)C1=CC=CC=C1 QQVNCBCBFNWLJX-KCHLEUMXSA-N 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-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
NSNPSJGHTQIXDO-UHFFFAOYSA-N naphthalene-1-carbonyl chloride Chemical compound C1=CC=C2C(C(=O)Cl)=CC=CC2=C1 NSNPSJGHTQIXDO-UHFFFAOYSA-N 0.000 description 1
DASJFYAPNPUBGG-UHFFFAOYSA-N naphthalene-1-sulfonyl chloride Chemical compound C1=CC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 DASJFYAPNPUBGG-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
125000004971 nitroalkyl group Chemical group 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000006201 parenteral dosage form Substances 0.000 description 1
239000008188 pellet Substances 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
229960005190 phenylalanine Drugs 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
239000012286 potassium permanganate Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000004237 preparative chromatography Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
238000005204 segregation Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
210000003802 sputum Anatomy 0.000 description 1
208000024794 sputum Diseases 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
229940014800 succinic anhydride Drugs 0.000 description 1
YALHCTUQSQRCSX-UHFFFAOYSA-N sulfane sulfuric acid Chemical compound S.OS(O)(=O)=O YALHCTUQSQRCSX-UHFFFAOYSA-N 0.000 description 1
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
230000008961 swelling Effects 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
XJJBXZIKXFOMLP-ZETCQYMHSA-N tert-butyl (2s)-pyrrolidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCCN1 XJJBXZIKXFOMLP-ZETCQYMHSA-N 0.000 description 1
ZHOGHVKKTOPFMY-UHFFFAOYSA-N tert-butyl 4-[(4-chlorophenyl)sulfonylcarbamoyl]benzoate Chemical compound C1=CC(C(=O)OC(C)(C)C)=CC=C1C(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 ZHOGHVKKTOPFMY-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
235000008521 threonine Nutrition 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-N trans-cinnamic acid Chemical compound OC(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-N 0.000 description 1
WRTMQOHKMFDUKX-UHFFFAOYSA-N triiodide Chemical compound I[I-]I WRTMQOHKMFDUKX-UHFFFAOYSA-N 0.000 description 1
229910052722 tritium Inorganic materials 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
235000002374 tyrosine Nutrition 0.000 description 1
238000000108 ultra-filtration Methods 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
150000003673 urethanes Chemical class 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
229960004295 valine Drugs 0.000 description 1
239000004474 valine Substances 0.000 description 1
238000005303 weighing Methods 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
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/13—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups
- C07C205/26—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups and being further substituted by halogen atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/01—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms
- C07C205/02—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms of a saturated carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/39—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups
- C07C205/42—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups having nitro groups or esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C205/43—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups having nitro groups or esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
- 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
- C07K5/0819—Tripeptides with the first amino acid being acidic
- 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
- C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
- 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)
Genetics & Genomics (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Molecular Biology (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Pulmonology (AREA)
Pain & Pain Management (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Rheumatology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Plural Heterocyclic Compounds (AREA)
Pyrrole Compounds (AREA)
Pyridine Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

SK395-86A 1985-01-22 1986-01-20 Peptide derivatives, method of its production and their use SK278095B6 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB858501523A GB8501523D0 (en)	1985-01-22	1985-01-22	Tripeptide derivatives
GB858501524A GB8501524D0 (en)	1985-01-22	1985-01-22	Tetrapeptide derivatives
GB858501522A GB8501522D0 (en)	1985-01-22	1985-01-22	Dipeptide derivatives

Publications (1)

Publication Number	Publication Date
SK278095B6 true SK278095B6 (en)	1995-12-06

Family

ID=27262565

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK395-86A SK278095B6 (en)	1985-01-22	1986-01-20	Peptide derivatives, method of its production and their use

Country Status (25)

Country	Link
US (2)	US4910190A (es)
EP (1)	EP0189305B1 (es)
JP (2)	JPH0759591B2 (es)
KR (1)	KR910002689B1 (es)
CN (1)	CN1027640C (es)
AU (1)	AU594658B2 (es)
CA (1)	CA1341023C (es)
CZ (1)	CZ278063B6 (es)
DE (1)	DE3686172T2 (es)
DK (1)	DK172736B1 (es)
ES (3)	ES8706169A1 (es)
FI (1)	FI84171C (es)
GB (1)	GB8600263D0 (es)
GR (1)	GR860169B (es)
HK (1)	HK18097A (es)
HU (1)	HU206370B (es)
IE (1)	IE58957B1 (es)
IL (1)	IL77680A (es)
NO (1)	NO169493C (es)
PH (1)	PH26575A (es)
PL (1)	PL150268B1 (es)
PT (1)	PT81887B (es)
SK (1)	SK278095B6 (es)
UA (1)	UA39093C2 (es)
ZW (1)	ZW1486A1 (es)

Families Citing this family (63)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5055450A (en) *	1985-01-22	1991-10-08	Ici Americas Inc.	Peptide derivatives
GB8600263D0 (en) *	1985-01-22	1986-02-12	Ici America Inc	Peptide derivatives
CA1341029C (en) *	1985-02-04	2000-06-20	Michael Kolb	Peptidase inhibitors
US5496927A (en) *	1985-02-04	1996-03-05	Merrell Pharmaceuticals Inc.	Peptidase inhibitors
ATE71934T1 (de) *	1985-06-07	1992-02-15	Ici America Inc	Selektionierte difluorverbindungen.
EP0276101A3 (en) *	1987-01-19	1989-11-23	Ici Americas Inc.	Substituted peptide derivatives
GB8809316D0 (en) *	1987-05-11	1988-05-25	Ici America Inc	Heterocyclic ketones
US5182263A (en) *	1988-04-25	1993-01-26	Hoffmann-La Roche Inc.	Analogs of tyrosine sulfate or tyrosine phosphate containing peptides
US5296608A (en) *	1988-04-25	1994-03-22	Hoffman-La Roche Inc.	Intermediates for analogs of tyrosine sulfate or tyrosine phosphate containing peptides
IL90872A0 (en) *	1988-07-08	1990-02-09	Smithkline Beckman Corp	Retroviral protease binding peptides
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GB8910547D0 (en) *	1989-05-08	1989-06-21	Ici America Inc	Substituted ketones
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1986
- 1986-01-07 GB GB868600263A patent/GB8600263D0/en active Pending
- 1986-01-20 DE DE8686300379T patent/DE3686172T2/de not_active Expired - Fee Related
- 1986-01-20 EP EP86300379A patent/EP0189305B1/en not_active Expired - Lifetime
- 1986-01-20 CZ CS86395A patent/CZ278063B6/cs not_active IP Right Cessation
- 1986-01-20 SK SK395-86A patent/SK278095B6/sk unknown
- 1986-01-21 UA UA4024099A patent/UA39093C2/uk unknown
- 1986-01-21 NO NO860190A patent/NO169493C/no not_active IP Right Cessation
- 1986-01-21 IE IE18086A patent/IE58957B1/en not_active IP Right Cessation
- 1986-01-21 PL PL1986257573A patent/PL150268B1/pl unknown
- 1986-01-21 ZW ZW14/86A patent/ZW1486A1/xx unknown
- 1986-01-21 FI FI860281A patent/FI84171C/fi not_active IP Right Cessation
- 1986-01-21 HU HU86276A patent/HU206370B/hu not_active IP Right Cessation
- 1986-01-21 DK DK198600308A patent/DK172736B1/da not_active IP Right Cessation
- 1986-01-21 GR GR860169A patent/GR860169B/el not_active IP Right Cessation
- 1986-01-22 JP JP61010328A patent/JPH0759591B2/ja not_active Expired - Fee Related
- 1986-01-22 IL IL77680A patent/IL77680A/xx not_active IP Right Cessation
- 1986-01-22 CA CA000500144A patent/CA1341023C/en not_active Expired - Fee Related
- 1986-01-22 ES ES551113A patent/ES8706169A1/es not_active Expired
- 1986-01-22 AU AU52623/86A patent/AU594658B2/en not_active Ceased
- 1986-01-22 CN CN86101066A patent/CN1027640C/zh not_active Expired - Lifetime
- 1986-01-22 KR KR1019860000375A patent/KR910002689B1/ko not_active Expired
- 1986-01-22 PT PT81887A patent/PT81887B/pt not_active IP Right Cessation
- 1986-09-01 ES ES557048A patent/ES8707551A1/es not_active Expired
1987
- 1987-01-20 US US07/005,538 patent/US4910190A/en not_active Expired - Lifetime
- 1987-01-30 ES ES557363A patent/ES8802526A1/es not_active Expired
1990
- 1990-04-27 PH PH33310A patent/PH26575A/en unknown
1992
- 1992-08-06 JP JP4210009A patent/JPH0680039B2/ja not_active Expired - Fee Related
1995
- 1995-06-06 US US08/467,333 patent/US5726158A/en not_active Expired - Fee Related
1997
- 1997-02-13 HK HK18097A patent/HK18097A/en not_active IP Right Cessation

Also Published As

Publication number	Publication date
CN1027640C (zh)	1995-02-15
ES557048A0 (es)	1987-08-01
GB8600263D0 (en)	1986-02-12
DK30886A (da)	1986-07-23
DK172736B1 (da)	1999-06-21
ES8802526A1 (es)	1988-07-01
PL150268B1 (en)	1990-05-31
EP0189305B1 (en)	1992-07-29
ES8707551A1 (es)	1987-08-01
PH26575A (en)	1992-08-19
IE860180L (en)	1986-07-22
KR910002689B1 (ko)	1991-05-03
FI860281A7 (fi)	1986-07-23
DE3686172T2 (de)	1993-01-14
JPH0759591B2 (ja)	1995-06-28
US4910190A (en)	1990-03-20
IE58957B1 (en)	1993-12-01
NO860190L (no)	1986-07-23
FI84171B (fi)	1991-07-15
HUT39464A (en)	1986-09-29
AU5262386A (en)	1986-07-31
PL257573A1 (en)	1987-03-23
PT81887A (en)	1986-02-01
HU206370B (en)	1992-10-28
NO169493C (no)	1992-07-01
PT81887B (pt)	1988-05-27
HK18097A (en)	1997-02-13
KR860005835A (ko)	1986-08-13
DK30886D0 (da)	1986-01-21
ZW1486A1 (en)	1987-09-30
ES8706169A1 (es)	1987-05-16
JPS61218518A (ja)	1986-09-29
FI84171C (fi)	1991-10-25
AU594658B2 (en)	1990-03-15
CN86101066A (zh)	1986-11-05
ES551113A0 (es)	1987-05-16
EP0189305A2 (en)	1986-07-30
UA39093C2 (uk)	2001-06-15
US5726158A (en)	1998-03-10
CA1341023C (en)	2000-06-13
JPH0680039B2 (ja)	1994-10-12
CZ278063B6 (en)	1993-08-11
GR860169B (en)	1986-05-15
IL77680A (en)	1990-12-23
ES557363A0 (es)	1988-07-01
CS39586A3 (en)	1992-01-15
FI860281A0 (fi)	1986-01-21
JPH05246984A (ja)	1993-09-24
EP0189305A3 (en)	1988-10-05
NO169493B (no)	1992-03-23
DE3686172D1 (de)	1992-09-03

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SK278095B6 (en)	1995-12-06	Peptide derivatives, method of its production and their use
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US5055450A (en)	1991-10-08	Peptide derivatives
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CA2056911C (en)	1998-09-22	Hiv protease inhibitors
EP0124317A2 (en)	1984-11-07	Proline derivatives
JPH06316594A (ja)	1994-11-15	カルボキシアルキルペプチド誘導体
EP0618221A2 (en)	1994-10-05	Heterocyclic inhibitors of farnesyl protein transferase
EP0132304A2 (en)	1985-01-30	Hydroxy substituted peptide compounds
SK105497A3 (en)	1997-12-10	Proline derivatives, preparation method thereof and pharmaceutical composition containing the same
KR0151783B1 (ko)	1998-10-15	신규의 프롤린 유도체
US5194588A (en)	1993-03-16	Aminoalcohol intermediates for peptide derivatives
FR2585708A1 (fr)	1987-02-06	Derives aminoalcools peptidiques inhibiteurs de la resine et des proteases acides, leur procede de preparation et leur application en therapeutique
US4552866A (en)	1985-11-12	Use of diamino alcohols as analgesic agents
US5242903A (en)	1993-09-07	Renin inhibitors
US4670541A (en)	1987-06-02	Use of diamino alcohols as analgesic agents
EP0762887B1 (en)	2001-09-26	Acylated enol derivatives as prodrugs of elastase inhibitors
JPH03500880A (ja)	1991-02-28	レニン阻害剤、その製造方法、その使用のための方法およびそれを含有する組成物
JPH06503315A (ja)	1994-04-14	シクロヘキシルスタチン型のレニン−抑制性ペプチド類、それらの製造方法および薬品中におけるそれらの使用
EP0353211A1 (en)	1990-01-31	New compounds
JP3409494B2 (ja)	2003-05-26	アザペプチド誘導体
FR2577931A1 (fr)	1986-08-29	Derives aminodiols peptidiques inhibiteurs de la renine et des proteases acides, leur procede de preparation et leur application en therapeutique
Digenis et al.	0	Peptide Elastase Inhibitors and Methods
HK1002112A (en)	1998-07-31	Heterocyclic inhibitors of farnesyl protein transferase