NO892564L - Nye typer korte renin-inhibitorer. - Google Patents
Nye typer korte renin-inhibitorer.Info
- Publication number
- NO892564L NO892564L NO89892564A NO892564A NO892564L NO 892564 L NO892564 L NO 892564L NO 89892564 A NO89892564 A NO 89892564A NO 892564 A NO892564 A NO 892564A NO 892564 L NO892564 L NO 892564L
- Authority
- NO
- Norway
- Prior art keywords
- cha
- carbon atoms
- production
- starting materials
- ala
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title description 5
- 238000004140 cleaning Methods 0.000 title 1
- 125000004432 carbon atom Chemical group C* 0.000 claims description 43
- 238000000034 method Methods 0.000 claims description 38
- 238000004519 manufacturing process Methods 0.000 claims description 34
- 150000001875 compounds Chemical class 0.000 claims description 28
- 239000007858 starting material Substances 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- -1 nitro, hydroxy Chemical group 0.000 claims description 14
- 150000001413 amino acids Chemical class 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 238000010647 peptide synthesis reaction Methods 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000004001 thioalkyl group Chemical group 0.000 claims description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 238000005160 1H NMR spectroscopy Methods 0.000 description 28
- 239000000243 solution Substances 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 206010020772 Hypertension Diseases 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 238000003786 synthesis reaction Methods 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
- 102000004881 Angiotensinogen Human genes 0.000 description 4
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 4
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 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 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 239000002461 renin inhibitor Substances 0.000 description 4
- 229940086526 renin-inhibitors Drugs 0.000 description 4
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 3
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 101800000734 Angiotensin-1 Proteins 0.000 description 3
- 102400000344 Angiotensin-1 Human genes 0.000 description 3
- 108090001067 Angiotensinogen Proteins 0.000 description 3
- 206010007559 Cardiac failure congestive Diseases 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010019280 Heart failures Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 108090000783 Renin Proteins 0.000 description 3
- 102100028255 Renin Human genes 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- SNDPXSYFESPGGJ-UHFFFAOYSA-N 2-aminopentanoic acid Chemical group CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 2
- RBLAOGBEJPHFHW-UHFFFAOYSA-N 2-benzyl-3-phenylpropanoic acid Chemical compound C=1C=CC=CC=1CC(C(=O)O)CC1=CC=CC=C1 RBLAOGBEJPHFHW-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 150000003862 amino acid derivatives Chemical class 0.000 description 2
- 150000001414 amino alcohols Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
- BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 description 1
- YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical compound O.O.O.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 YKFCISHFRZHKHY-NGQGLHOPSA-N 0.000 description 1
- RWPNRIDPFQODSJ-YFKPBYRVSA-N (2s)-2-amino-3-propan-2-yloxypropanoic acid Chemical compound CC(C)OC[C@H](N)C(O)=O RWPNRIDPFQODSJ-YFKPBYRVSA-N 0.000 description 1
- XGUXJMWPVJQIHI-YFKPBYRVSA-N (2s)-2-azaniumyl-3-cyclopropylpropanoate Chemical compound [O-]C(=O)[C@@H]([NH3+])CC1CC1 XGUXJMWPVJQIHI-YFKPBYRVSA-N 0.000 description 1
- PYUGLDKNALSSCS-UHFFFAOYSA-N (3-bromo-5-phenylpentyl)benzene Chemical compound C=1C=CC=CC=1CCC(Br)CCC1=CC=CC=C1 PYUGLDKNALSSCS-UHFFFAOYSA-N 0.000 description 1
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- PVHUJELLJLJGLN-INIZCTEOSA-N (S)-nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-INIZCTEOSA-N 0.000 description 1
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- LRHRHAWNXCGABU-UHFFFAOYSA-N 2-(cyclopentylazaniumyl)acetate Chemical compound OC(=O)CNC1CCCC1 LRHRHAWNXCGABU-UHFFFAOYSA-N 0.000 description 1
- WTOFYLAWDLQMBZ-UHFFFAOYSA-N 2-azaniumyl-3-thiophen-2-ylpropanoate Chemical group OC(=O)C(N)CC1=CC=CS1 WTOFYLAWDLQMBZ-UHFFFAOYSA-N 0.000 description 1
- KTZZIDWVKLDWBF-UHFFFAOYSA-N 2-azaniumyl-5,5,5-trifluoropentanoate Chemical group OC(=O)C(N)CCC(F)(F)F KTZZIDWVKLDWBF-UHFFFAOYSA-N 0.000 description 1
- VZYWYSRYMDGIMU-UHFFFAOYSA-N 2-benzyl-3-(4-hydroxyphenyl)propanoic acid Chemical compound C=1C=C(O)C=CC=1CC(C(=O)O)CC1=CC=CC=C1 VZYWYSRYMDGIMU-UHFFFAOYSA-N 0.000 description 1
- FREBZBMFAFFYKV-UHFFFAOYSA-N 2-benzyl-3-cyclohexylpropanoic acid Chemical compound C=1C=CC=CC=1CC(C(=O)O)CC1CCCCC1 FREBZBMFAFFYKV-UHFFFAOYSA-N 0.000 description 1
- GRTNKYWVTQFOKD-UHFFFAOYSA-N 2-benzyl-3-naphthalen-1-ylpropanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CC(C(=O)O)CC1=CC=CC=C1 GRTNKYWVTQFOKD-UHFFFAOYSA-N 0.000 description 1
- SDZBKSYBUWANHI-UHFFFAOYSA-N 2-benzyl-3-pyridin-4-ylpropanoic acid Chemical compound C=1C=NC=CC=1CC(C(=O)O)CC1=CC=CC=C1 SDZBKSYBUWANHI-UHFFFAOYSA-N 0.000 description 1
- JIVPVXMEBJLZRO-CQSZACIVSA-N 2-chloro-5-[(1r)-1-hydroxy-3-oxo-2h-isoindol-1-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC([C@@]2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-CQSZACIVSA-N 0.000 description 1
- SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 description 1
- WBJWXIQDBDZMAW-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carbonyl chloride Chemical compound C1=CC=CC2=C(C(Cl)=O)C(O)=CC=C21 WBJWXIQDBDZMAW-UHFFFAOYSA-N 0.000 description 1
- BZQGAPWJKAYCHR-UHFFFAOYSA-N 3,3-diphenylpropanoic acid Chemical compound C=1C=CC=CC=1C(CC(=O)O)C1=CC=CC=C1 BZQGAPWJKAYCHR-UHFFFAOYSA-N 0.000 description 1
- PXRXCDUFQVKJDR-UHFFFAOYSA-N 3-(2,3-dichlorophenyl)-2-[(2,3-dichlorophenyl)methyl]propanoic acid Chemical compound ClC1=C(CC(C(=O)O)CC2=C(C(=CC=C2)Cl)Cl)C=CC=C1Cl PXRXCDUFQVKJDR-UHFFFAOYSA-N 0.000 description 1
- KKTLDYWAUDBIRU-UHFFFAOYSA-N 3-(2,3-dimethylphenyl)-2-[(2,3-dimethylphenyl)methyl]propanoic acid Chemical compound CC1=CC=CC(CC(CC=2C(=C(C)C=CC=2)C)C(O)=O)=C1C KKTLDYWAUDBIRU-UHFFFAOYSA-N 0.000 description 1
- NOVBESKEIIKZQM-UHFFFAOYSA-N 3-(4-chlorophenyl)-2-[(4-chlorophenyl)methyl]propanoic acid Chemical compound C=1C=C(Cl)C=CC=1CC(C(=O)O)CC1=CC=C(Cl)C=C1 NOVBESKEIIKZQM-UHFFFAOYSA-N 0.000 description 1
- KQVRRMYFHYSGDC-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-2-[(4-hydroxyphenyl)methyl]propanoic acid Chemical compound C=1C=C(O)C=CC=1CC(C(=O)O)CC1=CC=C(O)C=C1 KQVRRMYFHYSGDC-UHFFFAOYSA-N 0.000 description 1
- VAUHEFFHRZPKDO-UHFFFAOYSA-N 3-(4-methoxyphenyl)-2-[(4-methoxyphenyl)methyl]propanoic acid Chemical compound C1=CC(OC)=CC=C1CC(C(O)=O)CC1=CC=C(OC)C=C1 VAUHEFFHRZPKDO-UHFFFAOYSA-N 0.000 description 1
- DQOFLUAWSNDDKP-UHFFFAOYSA-N 3-(4-nitrophenyl)-2-[(4-nitrophenyl)methyl]propanoic acid Chemical compound C=1C=C([N+]([O-])=O)C=CC=1CC(C(=O)O)CC1=CC=C([N+]([O-])=O)C=C1 DQOFLUAWSNDDKP-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- BXRLWGXPSRYJDZ-VKHMYHEASA-N 3-cyano-L-alanine Chemical compound OC(=O)[C@@H](N)CC#N BXRLWGXPSRYJDZ-VKHMYHEASA-N 0.000 description 1
- HYWIEQGSJZPUNG-UHFFFAOYSA-N 3-cyclohexyl-2-(cyclohexylmethyl)propanoic acid Chemical compound C1CCCCC1CC(C(=O)O)CC1CCCCC1 HYWIEQGSJZPUNG-UHFFFAOYSA-N 0.000 description 1
- JDXQWYKOKYUQDN-UHFFFAOYSA-N 3-hydroxypyrrolidine-2,5-dione Chemical class OC1CC(=O)NC1=O JDXQWYKOKYUQDN-UHFFFAOYSA-N 0.000 description 1
- RMTCEQSLPGEKAH-UHFFFAOYSA-N 3-naphthalen-1-yl-2-(naphthalen-1-ylmethyl)propanoic acid Chemical compound C1=CC=C2C(CC(CC=3C4=CC=CC=C4C=CC=3)C(=O)O)=CC=CC2=C1 RMTCEQSLPGEKAH-UHFFFAOYSA-N 0.000 description 1
- VCQHSKUQMUWHHT-UHFFFAOYSA-N 3-thiophen-2-yl-2-(thiophen-2-ylmethyl)propanoic acid Chemical compound C=1C=CSC=1CC(C(=O)O)CC1=CC=CS1 VCQHSKUQMUWHHT-UHFFFAOYSA-N 0.000 description 1
- ZSDJHOFUWZAZOJ-UHFFFAOYSA-N 4-phenyl-2-(2-phenylethyl)butanoic acid Chemical compound C=1C=CC=CC=1CCC(C(=O)O)CCC1=CC=CC=C1 ZSDJHOFUWZAZOJ-UHFFFAOYSA-N 0.000 description 1
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
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- C07K—PEPTIDES
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- C07K7/04—Linear peptides containing only normal peptide links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C317/28—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Landscapes
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE8802428A SE8802428D0 (sv) | 1988-06-28 | 1988-06-28 | New compounds |
Publications (2)
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| NO892564D0 NO892564D0 (no) | 1989-06-21 |
| NO892564L true NO892564L (no) | 1989-12-29 |
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|---|---|---|---|
| NO89892564A NO892564L (no) | 1988-06-28 | 1989-06-21 | Nye typer korte renin-inhibitorer. |
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| EP (1) | EP0353211A1 (fi) |
| JP (1) | JPH0285245A (fi) |
| KR (1) | KR900000383A (fi) |
| CN (1) | CN1039028A (fi) |
| AU (1) | AU3671189A (fi) |
| DD (1) | DD284027A5 (fi) |
| DK (1) | DK300989A (fi) |
| FI (1) | FI893118A (fi) |
| HU (1) | HUT51291A (fi) |
| NO (1) | NO892564L (fi) |
| PT (1) | PT90992A (fi) |
| SE (1) | SE8802428D0 (fi) |
| YU (1) | YU132789A (fi) |
| ZA (1) | ZA894544B (fi) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991009838A1 (en) * | 1989-12-22 | 1991-07-11 | Aktiebolaget Astra | New amides |
| US5317039A (en) * | 1992-07-20 | 1994-05-31 | G. D. Searle & Co. | Cyclopropyl-alanine aryl/alkylsulfide/sulfonyl-terminated amino-diol compounds for treatment of hypertension |
| US5314920A (en) * | 1992-07-20 | 1994-05-24 | G. D. Searle & Co. | Ethynyl-alanine aryl/alkylsulfonyl-terminated amino-diol compounds for treatment of hypertension |
| US8168616B1 (en) * | 2000-11-17 | 2012-05-01 | Novartis Ag | Combination comprising a renin inhibitor and an angiotensin receptor inhibitor for hypertension |
| KR20010088472A (ko) * | 2001-07-19 | 2001-09-28 | 이강섭 | 석재, 철, 콘크리트, 목재, 플라스틱 등 기존의 모든물건의 바탕에 자연적으로 대리석 무늬를 형성하는 공법 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4645759A (en) * | 1984-06-22 | 1987-02-24 | Abbott Laboratories | Renin inhibiting compounds |
| WO1987004349A1 (en) * | 1986-01-16 | 1987-07-30 | Joseph Dellaria | Peptide analogs |
| EP0321497A1 (en) * | 1986-09-30 | 1989-06-28 | The Upjohn Company | Renin inhibitory peptides having novel c-terminal moieties |
| SE8605573D0 (sv) * | 1986-12-29 | 1986-12-29 | Haessle Ab | Novel compounds |
-
1988
- 1988-06-28 SE SE8802428A patent/SE8802428D0/xx unknown
-
1989
- 1989-06-14 ZA ZA894544A patent/ZA894544B/xx unknown
- 1989-06-19 DK DK300989A patent/DK300989A/da unknown
- 1989-06-20 EP EP89850205A patent/EP0353211A1/en not_active Withdrawn
- 1989-06-21 NO NO89892564A patent/NO892564L/no unknown
- 1989-06-22 AU AU36711/89A patent/AU3671189A/en not_active Abandoned
- 1989-06-27 PT PT90992A patent/PT90992A/pt not_active Application Discontinuation
- 1989-06-27 DD DD89330012A patent/DD284027A5/de not_active IP Right Cessation
- 1989-06-27 FI FI893118A patent/FI893118A/fi not_active Application Discontinuation
- 1989-06-27 KR KR1019890008878A patent/KR900000383A/ko not_active Application Discontinuation
- 1989-06-27 JP JP1162851A patent/JPH0285245A/ja active Pending
- 1989-06-27 HU HU893239A patent/HUT51291A/hu unknown
- 1989-06-28 YU YU132789A patent/YU132789A/sh unknown
- 1989-06-28 CN CN89104514A patent/CN1039028A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DK300989A (da) | 1989-12-29 |
| KR900000383A (ko) | 1990-01-30 |
| FI893118A (fi) | 1989-12-29 |
| DK300989D0 (da) | 1989-06-19 |
| NO892564D0 (no) | 1989-06-21 |
| AU3671189A (en) | 1990-01-04 |
| CN1039028A (zh) | 1990-01-24 |
| JPH0285245A (ja) | 1990-03-26 |
| SE8802428D0 (sv) | 1988-06-28 |
| HUT51291A (en) | 1990-04-28 |
| PT90992A (pt) | 1989-12-29 |
| ZA894544B (en) | 1990-07-25 |
| YU132789A (sh) | 1992-09-07 |
| EP0353211A1 (en) | 1990-01-31 |
| DD284027A5 (de) | 1990-10-31 |
| FI893118A0 (fi) | 1989-06-27 |
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