IL101633A - History of dipeptide transformed by phosphono / biarril, their preparation and pharmaceutical preparations containing them - Google Patents
History of dipeptide transformed by phosphono / biarril, their preparation and pharmaceutical preparations containing themInfo
- Publication number
- IL101633A IL101633A IL10163392A IL10163392A IL101633A IL 101633 A IL101633 A IL 101633A IL 10163392 A IL10163392 A IL 10163392A IL 10163392 A IL10163392 A IL 10163392A IL 101633 A IL101633 A IL 101633A
- Authority
- IL
- Israel
- Prior art keywords
- pharmaceutically acceptable
- propionyl
- acceptable salt
- biphenylyl
- phosphonomethylamino
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 19
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 title claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 12
- 108010016626 Dipeptides Proteins 0.000 title abstract description 5
- 125000005841 biaryl group Chemical group 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 157
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 124
- -1 6-tetrahydronaphthyl Chemical group 0.000 claims abstract description 118
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 67
- 101100295738 Gallus gallus COR3 gene Proteins 0.000 claims abstract description 53
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 46
- 238000000034 method Methods 0.000 claims abstract description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 44
- 239000001257 hydrogen Substances 0.000 claims abstract description 44
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 42
- 150000002148 esters Chemical class 0.000 claims abstract description 35
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 32
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 31
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 29
- 150000002367 halogens Chemical class 0.000 claims abstract description 29
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 23
- 102000003729 Neprilysin Human genes 0.000 claims abstract description 20
- 108090000028 Neprilysin Proteins 0.000 claims abstract description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 18
- 150000001408 amides Chemical class 0.000 claims abstract description 17
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 16
- 125000005236 alkanoylamino group Chemical group 0.000 claims abstract description 12
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 12
- 125000002541 furyl group Chemical group 0.000 claims abstract description 12
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 12
- 125000003118 aryl group Chemical group 0.000 claims abstract description 11
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 10
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 10
- 125000001424 substituent group Chemical group 0.000 claims abstract description 10
- 125000005042 acyloxymethyl group Chemical group 0.000 claims abstract description 9
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
- 125000004956 cyclohexylene group Chemical group 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 163
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 57
- 239000000203 mixture Substances 0.000 claims description 37
- 239000002253 acid Substances 0.000 claims description 31
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 21
- 229910052701 rubidium Inorganic materials 0.000 claims description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- 230000008569 process Effects 0.000 claims description 15
- 125000003282 alkyl amino group Chemical group 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 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 claims description 12
- 229910052705 radium Inorganic materials 0.000 claims description 12
- 239000011734 sodium Substances 0.000 claims description 12
- JTQWXNZXTRVPHN-LJAQVGFWSA-N 3-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)NCCC(=O)O)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 JTQWXNZXTRVPHN-LJAQVGFWSA-N 0.000 claims description 11
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 11
- 229940002612 prodrug Drugs 0.000 claims description 11
- 239000000651 prodrug Substances 0.000 claims description 11
- 229910052708 sodium Inorganic materials 0.000 claims description 11
- 125000002837 carbocyclic group Chemical group 0.000 claims description 10
- 150000005690 diesters Chemical class 0.000 claims description 9
- 125000006239 protecting group Chemical group 0.000 claims description 9
- 125000002704 decyl group Chemical group [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])* 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 8
- 230000003287 optical effect Effects 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 6
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 5
- UQBLGLVSPFTLIG-DMVZSUBZSA-N [[(2s)-1-[(4-ethoxycarbonylcyclohexyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C1CC(C(=O)OCC)CCC1NC(=O)[C@@H](NCP(O)(=O)OC=1C=CC=CC=1)CC1=CC=C(C=2C=CC=CC=2)C=C1 UQBLGLVSPFTLIG-DMVZSUBZSA-N 0.000 claims description 5
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000000524 functional group Chemical group 0.000 claims description 5
- 125000004955 1,4-cyclohexylene group Chemical group [H]C1([H])C([H])([H])C([H])([*:1])C([H])([H])C([H])([H])C1([H])[*:2] 0.000 claims description 4
- MVRLTBIHUWUGAR-KRWDZBQOSA-N 3-[[(2s)-3-(4-phenylphenyl)-2-(phosphonomethylamino)propanoyl]amino]propanoic acid Chemical compound C1=CC(C[C@@H](C(=O)NCCC(=O)O)NCP(O)(O)=O)=CC=C1C1=CC=CC=C1 MVRLTBIHUWUGAR-KRWDZBQOSA-N 0.000 claims description 4
- UUISNSYMVJLWRI-NDEPHWFRSA-N [[(2S)-1-[(3-ethoxy-3-oxopropyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-(4-propan-2-ylphenoxy)phosphinic acid Chemical compound C(C)(C)C1=CC=C(C=C1)OP(=O)(O)CN[C@H](C(=O)NCCC(=O)OCC)CC1=CC=C(C=C1)C1=CC=CC=C1 UUISNSYMVJLWRI-NDEPHWFRSA-N 0.000 claims description 4
- MNOUSNXSLUCSCK-SANMLTNESA-N [[(2S)-1-[(3-ethoxy-3-oxopropyl)amino]-3-[4-(4-methylphenyl)phenyl]-1-oxopropan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C1(=CC=CC=C1)OP(=O)(O)CN[C@H](C(=O)NCCC(=O)OCC)CC1=CC=C(C=C1)C1=CC=C(C=C1)C MNOUSNXSLUCSCK-SANMLTNESA-N 0.000 claims description 4
- 229960003767 alanine Drugs 0.000 claims description 4
- WDXHEDSUUDLQKV-BHVANESWSA-N benzyl 3-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]propanoate Chemical compound C([C@@H](C(=O)NCCC(=O)OCC=1C=CC=CC=1)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 WDXHEDSUUDLQKV-BHVANESWSA-N 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- GTTBQSNGUYHPNK-UHFFFAOYSA-N hydroxymethylphosphonic acid Chemical class OCP(O)(O)=O GTTBQSNGUYHPNK-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- IQSVRHNNAPSJHM-MHZLTWQESA-N (3,4-dimethylphenoxy)-[[[(2S)-1-[(3-ethoxy-3-oxopropyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl]phosphinic acid Chemical compound C([C@@H](C(=O)NCCC(=O)OCC)NCP(O)(=O)OC=1C=C(C)C(C)=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 IQSVRHNNAPSJHM-MHZLTWQESA-N 0.000 claims description 2
- YEPZOYCLNPHLRE-MHZLTWQESA-N (4-acetamidophenoxy)-[[[(2S)-1-[(3-ethoxy-3-oxopropyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl]phosphinic acid Chemical compound C(C)(=O)NC1=CC=C(C=C1)OP(=O)(O)CN[C@H](C(=O)NCCC(=O)OCC)CC1=CC=C(C=C1)C1=CC=CC=C1 YEPZOYCLNPHLRE-MHZLTWQESA-N 0.000 claims description 2
- DHCDIFCDUYITKF-LHEWISCISA-N 2,3-dihydro-1h-inden-5-yl 3-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]propanoate Chemical compound C([C@@H](C(=O)NCCC(=O)OC=1C=C2CCCC2=CC=1)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 DHCDIFCDUYITKF-LHEWISCISA-N 0.000 claims description 2
- MFCBQBHMDPFEHT-NDEPHWFRSA-N 2-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]acetic acid Chemical compound C([C@@H](C(=O)NCC(=O)O)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 MFCBQBHMDPFEHT-NDEPHWFRSA-N 0.000 claims description 2
- RCGSYJNOCWJPHN-UHFFFAOYSA-N 2-[[3-(4-phenylphenyl)-2-(phosphonomethylamino)propanoyl]amino]acetic acid Chemical compound C1=CC(CC(C(=O)NCC(=O)O)NCP(O)(O)=O)=CC=C1C1=CC=CC=C1 RCGSYJNOCWJPHN-UHFFFAOYSA-N 0.000 claims description 2
- NCFHYHJBBXCKNL-XIFFEERXSA-N 3-[[(2s)-2-[bis(3,5-dimethylphenoxy)phosphorylmethylamino]-3-(4-phenylphenyl)propanoyl]amino]propanoic acid Chemical compound CC1=CC(C)=CC(OP(=O)(CN[C@@H](CC=2C=CC(=CC=2)C=2C=CC=CC=2)C(=O)NCCC(O)=O)OC=2C=C(C)C=C(C)C=2)=C1 NCFHYHJBBXCKNL-XIFFEERXSA-N 0.000 claims description 2
- PQDGRRSQMPARMF-HKBQPEDESA-N 3-[[(2s)-2-[bis(4-methylphenoxy)phosphorylmethylamino]-3-(4-phenylphenyl)propanoyl]amino]propanoic acid Chemical compound C1=CC(C)=CC=C1OP(=O)(OC=1C=CC(C)=CC=1)CN[C@H](C(=O)NCCC(O)=O)CC1=CC=C(C=2C=CC=CC=2)C=C1 PQDGRRSQMPARMF-HKBQPEDESA-N 0.000 claims description 2
- RMTSQBXDRRSABG-DHUJRADRSA-N 3-[[(2s)-2-[bis(4-propylphenoxy)phosphorylmethylamino]-3-(4-phenylphenyl)propanoyl]amino]propanoic acid Chemical compound C1=CC(CCC)=CC=C1OP(=O)(OC=1C=CC(CCC)=CC=1)CN[C@H](C(=O)NCCC(O)=O)CC1=CC=C(C=2C=CC=CC=2)C=C1 RMTSQBXDRRSABG-DHUJRADRSA-N 0.000 claims description 2
- XWWOVHXDWDESFU-UHFFFAOYSA-N 3-[[3-[4-(4-chlorophenyl)phenyl]-2-(phosphonomethylamino)propanoyl]amino]propanoic acid Chemical compound C1=CC(CC(C(=O)NCCC(=O)O)NCP(O)(O)=O)=CC=C1C1=CC=C(Cl)C=C1 XWWOVHXDWDESFU-UHFFFAOYSA-N 0.000 claims description 2
- PEYZSBTXPKKOQO-UHFFFAOYSA-N 3-[[3-[4-(4-fluorophenyl)phenyl]-2-(phosphonomethylamino)propanoyl]amino]propanoic acid Chemical compound C1=CC(CC(C(=O)NCCC(=O)O)NCP(O)(O)=O)=CC=C1C1=CC=C(F)C=C1 PEYZSBTXPKKOQO-UHFFFAOYSA-N 0.000 claims description 2
- TXVBIXDCBBXVGM-UHFFFAOYSA-N 3-[[3-[4-(4-methylphenyl)phenyl]-2-(phosphonomethylamino)propanoyl]amino]propanoic acid Chemical compound C1=CC(C)=CC=C1C1=CC=C(CC(NCP(O)(O)=O)C(=O)NCCC(O)=O)C=C1 TXVBIXDCBBXVGM-UHFFFAOYSA-N 0.000 claims description 2
- ZQJJZDCJRCZVAZ-XIFFEERXSA-N 4-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC(=O)[C@@H](NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)CC1=CC=C(C=2C=CC=CC=2)C=C1 ZQJJZDCJRCZVAZ-XIFFEERXSA-N 0.000 claims description 2
- JDKUZYYBXRCCFM-NRFANRHFSA-N 4-[[(2s)-3-(4-phenylphenyl)-2-(phosphonomethylamino)propanoyl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC(=O)[C@@H](NCP(O)(O)=O)CC1=CC=C(C=2C=CC=CC=2)C=C1 JDKUZYYBXRCCFM-NRFANRHFSA-N 0.000 claims description 2
- YCAYWUROMGUTCF-UHFFFAOYSA-N 4-[[3-(4-phenylphenyl)-2-(phosphonomethylamino)propanoyl]amino]cyclohexane-1-carboxylic acid Chemical compound C1CC(C(=O)O)CCC1NC(=O)C(NCP(O)(O)=O)CC1=CC=C(C=2C=CC=CC=2)C=C1 YCAYWUROMGUTCF-UHFFFAOYSA-N 0.000 claims description 2
- NWHYZBREGJOASX-UHFFFAOYSA-N 7-[[3-(4-phenylphenyl)-2-(phosphonomethylamino)propanoyl]amino]heptanoic acid Chemical compound C1=CC(CC(C(=O)NCCCCCCC(=O)O)NCP(O)(O)=O)=CC=C1C1=CC=CC=C1 NWHYZBREGJOASX-UHFFFAOYSA-N 0.000 claims description 2
- WWTNQTLNGVQJNP-UHFFFAOYSA-N C(C(C)C)(=O)OCC(P(=O)(O)O)(NC(C(=O)NCCC(=O)OCC)CC1=CC=C(C=C1)C1=CC=CC=C1)COC(C(C)C)=O Chemical compound C(C(C)C)(=O)OCC(P(=O)(O)O)(NC(C(=O)NCCC(=O)OCC)CC1=CC=C(C=C1)C1=CC=CC=C1)COC(C(C)C)=O WWTNQTLNGVQJNP-UHFFFAOYSA-N 0.000 claims description 2
- FPHSLIJVXMWQJC-NDEPHWFRSA-N C([C@@H](C(=O)NCCC(=O)OCC)N(CP(O)(O)=O)C=1C=C2CCCC2=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 Chemical compound C([C@@H](C(=O)NCCC(=O)OCC)N(CP(O)(O)=O)C=1C=C2CCCC2=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 FPHSLIJVXMWQJC-NDEPHWFRSA-N 0.000 claims description 2
- XEUJBBIFTMMOCB-HKBQPEDESA-N COC1=CC=C(C=C1)OP(=O)(O)CN[C@H](C(=O)NCCC(=O)OCC1=CC=CC=C1)CC1=CC=C(C=C1)C1=CC=CC=C1 Chemical compound COC1=CC=C(C=C1)OP(=O)(O)CN[C@H](C(=O)NCCC(=O)OCC1=CC=CC=C1)CC1=CC=C(C=C1)C1=CC=CC=C1 XEUJBBIFTMMOCB-HKBQPEDESA-N 0.000 claims description 2
- 239000004471 Glycine Substances 0.000 claims description 2
- POAXRLIGJNLEFJ-SANMLTNESA-N [[(2S)-1-[(3-ethoxy-3-oxopropyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-(4-methylphenoxy)phosphinic acid Chemical compound CC1=CC=C(C=C1)OP(=O)(O)CN[C@H](C(=O)NCCC(=O)OCC)CC1=CC=C(C=C1)C1=CC=CC=C1 POAXRLIGJNLEFJ-SANMLTNESA-N 0.000 claims description 2
- LQVMIFLUPJGXKP-NDEPHWFRSA-N [[(2S)-1-[(3-ethoxy-3-oxopropyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-(4-propylphenoxy)phosphinic acid Chemical compound C(CC)C1=CC=C(C=C1)OP(=O)(O)CN[C@H](C(=O)NCCC(=O)OCC)CC1=CC=C(C=C1)C1=CC=CC=C1 LQVMIFLUPJGXKP-NDEPHWFRSA-N 0.000 claims description 2
- JUSLIBLEBQFXHK-NDEPHWFRSA-N [[(2s)-1-(4-methoxycarbonylanilino)-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C1=CC(C(=O)OC)=CC=C1NC(=O)[C@@H](NCP(O)(=O)OC=1C=CC=CC=1)CC1=CC=C(C=2C=CC=CC=2)C=C1 JUSLIBLEBQFXHK-NDEPHWFRSA-N 0.000 claims description 2
- UWJVDOOSSQISRC-VWLOTQADSA-N [[(2s)-1-[(3-ethoxy-3-oxopropyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C([C@@H](C(=O)NCCC(=O)OCC)NCP(O)(=O)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 UWJVDOOSSQISRC-VWLOTQADSA-N 0.000 claims description 2
- DGTMRKJUYSNQHH-DEOSSOPVSA-N [[(2s)-1-[(3-methoxy-3-oxopropyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C([C@@H](C(=O)NCCC(=O)OC)NCP(O)(=O)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 DGTMRKJUYSNQHH-DEOSSOPVSA-N 0.000 claims description 2
- NCKZGTCKSANCNX-SANMLTNESA-N [[(2s)-1-[(4-ethoxy-4-oxobutyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C([C@@H](C(=O)NCCCC(=O)OCC)NCP(O)(=O)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 NCKZGTCKSANCNX-SANMLTNESA-N 0.000 claims description 2
- XEYDGCVRBXPKTF-LJAQVGFWSA-N [[(2s)-1-[(7-ethoxy-7-oxoheptyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C([C@@H](C(=O)NCCCCCCC(=O)OCC)NCP(O)(=O)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 XEYDGCVRBXPKTF-LJAQVGFWSA-N 0.000 claims description 2
- UTHFQNVANYBPJU-YTTGMZPUSA-N [[(2s)-1-[[3-(2,3-dihydro-1h-inden-5-yloxy)-3-oxopropyl]amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C([C@H](NCP(=O)(O)OC=1C=CC=CC=1)C(=O)NCCC(=O)OC=1C=C2CCCC2=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 UTHFQNVANYBPJU-YTTGMZPUSA-N 0.000 claims description 2
- YKKZHAROJOALLS-NDEPHWFRSA-N [[(2s)-1-[[3-[2-(diethylamino)-2-oxoethoxy]-3-oxopropyl]amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C([C@@H](C(=O)NCCC(=O)OCC(=O)N(CC)CC)NCP(O)(=O)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 YKKZHAROJOALLS-NDEPHWFRSA-N 0.000 claims description 2
- HHDKPTVOIUHECP-PMERELPUSA-N [[(2s)-1-oxo-1-[(3-oxo-3-phenylmethoxypropyl)amino]-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C([C@H](NCP(=O)(O)OC=1C=CC=CC=1)C(=O)NCCC(=O)OCC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 HHDKPTVOIUHECP-PMERELPUSA-N 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 230000002452 interceptive effect Effects 0.000 claims description 2
- 150000005691 triesters Chemical class 0.000 claims description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 2
- JTQWXNZXTRVPHN-GDLZYMKVSA-N 3-[[(2r)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]propanoic acid Chemical compound C([C@H](C(=O)NCCC(=O)O)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 JTQWXNZXTRVPHN-GDLZYMKVSA-N 0.000 claims 1
- ZXOPQUSBNQPMNQ-PMERELPUSA-N 3-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-[4-(4-methylphenyl)phenyl]propanoyl]amino]propanoic acid Chemical compound C1=CC(C)=CC=C1C(C=C1)=CC=C1C[C@@H](C(=O)NCCC(O)=O)NCP(=O)(OC=1C=CC=CC=1)OC1=CC=CC=C1 ZXOPQUSBNQPMNQ-PMERELPUSA-N 0.000 claims 1
- BPKFIWFJWKLOGF-SANMLTNESA-N 3-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-[4-(furan-2-yl)phenyl]propanoyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)NCCC(=O)O)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CO1 BPKFIWFJWKLOGF-SANMLTNESA-N 0.000 claims 1
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- 235000011852 gelatine desserts Nutrition 0.000 description 1
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical class OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 1
- XDDAORKBJWWYJS-UHFFFAOYSA-N glyphosate Chemical compound OC(=O)CNCP(O)(O)=O XDDAORKBJWWYJS-UHFFFAOYSA-N 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- PELJISAVHGXLAL-UHFFFAOYSA-N iodomethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCI PELJISAVHGXLAL-UHFFFAOYSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 210000000231 kidney cortex Anatomy 0.000 description 1
- DWKPPFQULDPWHX-VKHMYHEASA-N l-alanyl ester Chemical compound COC(=O)[C@H](C)N DWKPPFQULDPWHX-VKHMYHEASA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000005291 magnetic effect Effects 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- RFKMCNOHBTXSMU-UHFFFAOYSA-N methoxyflurane Chemical compound COC(F)(F)C(Cl)Cl RFKMCNOHBTXSMU-UHFFFAOYSA-N 0.000 description 1
- 229960002455 methoxyflurane Drugs 0.000 description 1
- RYYDMSMPNITDHP-RSAXXLAASA-N methyl (2s)-2-amino-3-(4-phenylphenyl)propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=CC=C1 RYYDMSMPNITDHP-RSAXXLAASA-N 0.000 description 1
- YLPJWJSNTYILCW-YDALLXLXSA-N methyl (2s)-2-amino-3-(4-thiophen-2-ylphenyl)propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=CS1 YLPJWJSNTYILCW-YDALLXLXSA-N 0.000 description 1
- NCIPTOKUHQWFBY-NTISSMGPSA-N methyl (2s)-2-amino-3-[4-(4-methylphenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(C)C=C1 NCIPTOKUHQWFBY-NTISSMGPSA-N 0.000 description 1
- NQIFXJSLCUJHBB-LBPRGKRZSA-N methyl (2s)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1=CC=C(O)C=C1 NQIFXJSLCUJHBB-LBPRGKRZSA-N 0.000 description 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- LZXXNPOYQCLXRS-UHFFFAOYSA-N methyl 4-aminobenzoate Chemical compound COC(=O)C1=CC=C(N)C=C1 LZXXNPOYQCLXRS-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 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
- 235000019426 modified starch Nutrition 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 150000002780 morpholines Chemical class 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
- 238000013059 nephrectomy Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000004717 pyruvic acids Chemical class 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229920000260 silastic Polymers 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- SLZHLQUFNFXTHB-UHFFFAOYSA-M sodium;5-butan-2-yl-5-ethyl-2-sulfanylidenepyrimidin-3-ide-4,6-dione Chemical compound [Na+].CCC(C)C1(CC)C([O-])=NC(=S)NC1=O SLZHLQUFNFXTHB-UHFFFAOYSA-M 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960005453 strychnine Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000005622 tetraalkylammonium hydroxides Chemical class 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 230000002883 vasorelaxation effect Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 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
- C07K5/06—Dipeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
- C07F9/655345—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
-
- 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
-
- 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)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/694,533 US5155100A (en) | 1991-05-01 | 1991-05-01 | Phosphono/biaryl substituted dipeptide derivatives |
Publications (2)
Publication Number | Publication Date |
---|---|
IL101633A0 IL101633A0 (en) | 1992-12-30 |
IL101633A true IL101633A (en) | 1996-03-31 |
Family
ID=24789228
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL10163392A IL101633A (en) | 1991-05-01 | 1992-04-17 | History of dipeptide transformed by phosphono / biarril, their preparation and pharmaceutical preparations containing them |
Country Status (15)
Country | Link |
---|---|
US (1) | US5155100A (xx) |
EP (1) | EP0511940A3 (xx) |
JP (1) | JPH05170792A (xx) |
KR (1) | KR920021578A (xx) |
AU (1) | AU655252B2 (xx) |
CA (1) | CA2067592A1 (xx) |
FI (1) | FI921884A (xx) |
HU (1) | HUT61032A (xx) |
IE (1) | IE921401A1 (xx) |
IL (1) | IL101633A (xx) |
MX (1) | MX9201953A (xx) |
NO (1) | NO921719L (xx) |
NZ (1) | NZ242546A (xx) |
TW (1) | TW208704B (xx) |
ZA (1) | ZA923164B (xx) |
Families Citing this family (57)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5177064A (en) * | 1990-07-13 | 1993-01-05 | University Of Florida | Targeted drug delivery via phosphonate derivatives |
US5294632A (en) * | 1991-05-01 | 1994-03-15 | Ciba-Geigy Corporation | Phosphono/biaryl substituted dipetide derivatives |
US5250522A (en) * | 1992-10-09 | 1993-10-05 | Ciba-Geigy Corporation | Phosphono/biaryl substituted amino acid derivatives |
JP3130938B2 (ja) * | 1991-10-22 | 2001-01-31 | オーストリア・タバクヴェルケ・アクチエンゲゼルシャフトヴォマー・オーシュターライヒッシェ・タバコレジー | シガレットフィルター |
US5273990A (en) * | 1992-09-03 | 1993-12-28 | Ciba-Geigy Corporation | Phosphono substituted tetrazole derivatives |
JPH05148277A (ja) * | 1991-11-05 | 1993-06-15 | Banyu Pharmaceut Co Ltd | アミノホスホン酸誘導体 |
IT1266570B1 (it) * | 1993-07-30 | 1997-01-09 | Zambon Spa | Derivati della propanammide n-eteroaril sostituiti utili nel trattamento delle malattie cardiovascolari |
WO1995013817A1 (en) * | 1993-11-18 | 1995-05-26 | Smithkline Beecham Corporation | Endothelin converting enzyme inhibitors |
IT1274673B (it) * | 1994-04-14 | 1997-07-24 | Zambon Spa | Derivati dell'acido fosfonico utili nel trattamento delle malattie car.iovascolari |
IT1270260B (it) * | 1994-06-21 | 1997-04-29 | Zambon Spa | Derivati dell'acido fosfonico ad attivita' inibitrice delle metallopeptidasi |
US5583123A (en) * | 1994-12-22 | 1996-12-10 | Ciba-Geigy Corporation | Certain tetrazole derivatives |
US5635103A (en) | 1995-01-20 | 1997-06-03 | The Procter & Gamble Company | Bleaching compositions and additives comprising bleach activators having alpha-modified lactam leaving-groups |
US5550119A (en) * | 1995-03-02 | 1996-08-27 | Ciba-Geigy Corporation | Phosphono substituted tetrazole derivatives as ECE inhibitors |
AU7211696A (en) * | 1995-09-27 | 1997-04-17 | Ciba-Geigy Ag | Treatment of chronic progressive renal failure |
JP3973748B2 (ja) * | 1998-01-14 | 2007-09-12 | 花王株式会社 | 発毛抑制剤 |
MXPA01009654A (es) * | 1999-03-29 | 2002-05-14 | Squibb Bristol Myers Co | Uso de inhibidores de la vasopeptidasa para tratar la angina de pecho. |
JP2007191446A (ja) * | 2006-01-20 | 2007-08-02 | Sumitomo Chemical Co Ltd | ビフェニルメチルヒダントイン化合物、その製造方法、及びそれを用いるビフェニルアラニン化合物の製造方法 |
WO2007083774A1 (ja) * | 2006-01-17 | 2007-07-26 | Sumitomo Chemical Company, Limited | ビフェニルメチルヒダントイン化合物、その製造方法、及びそれを用いるビフェニルアラニン化合物の製造方法 |
TW200838501A (en) * | 2007-02-02 | 2008-10-01 | Theravance Inc | Dual-acting antihypertensive agents |
JP2008260755A (ja) * | 2007-03-20 | 2008-10-30 | Sumitomo Chemical Co Ltd | L−ビフェニルアラニン化合物の塩の回収方法、およびそれを用いたビフェニルアラニンエステル化合物の回収方法 |
TWI448284B (zh) * | 2007-04-24 | 2014-08-11 | Theravance Inc | 雙效抗高血壓劑 |
TWI406850B (zh) * | 2007-06-05 | 2013-09-01 | Theravance Inc | 雙效苯并咪唑抗高血壓劑 |
WO2009035543A1 (en) | 2007-09-07 | 2009-03-19 | Theravance, Inc. | Dual-acting antihypertensive agents |
CA2705921A1 (en) | 2007-12-11 | 2009-06-18 | Theravance, Inc. | Dual-acting benzoimidazole derivatives and their use as antihypertensive agents |
US7989484B2 (en) | 2008-04-29 | 2011-08-02 | Theravance, Inc. | Dual-acting antihypertensive agents |
US7863309B2 (en) | 2008-07-24 | 2011-01-04 | Theravance, Inc. | Dual-acting antihypertensive agents |
JP5833000B2 (ja) | 2009-07-07 | 2015-12-16 | セラヴァンス バイオファーマ アール&ディー アイピー, エルエルシー | 二重に作用するピラゾール抗高血圧症薬 |
WO2011011232A1 (en) | 2009-07-22 | 2011-01-27 | Theravance, Inc. | Dual-acting oxazole antihypertensive agents |
US8481549B2 (en) | 2010-01-19 | 2013-07-09 | Theravance, Inc. | Dual-acting thiophene, pyrrole, thiazole and furan antihypertensive agents |
US8993631B2 (en) | 2010-11-16 | 2015-03-31 | Novartis Ag | Method of treating contrast-induced nephropathy |
JP5944921B2 (ja) | 2010-12-15 | 2016-07-05 | セラヴァンス バイオファーマ アール&ディー アイピー, エルエルシー | ネプリライシン阻害剤 |
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DE141930C (xx) * | 1900-01-01 | |||
US4053505A (en) * | 1976-01-05 | 1977-10-11 | Monsanto Company | Preparation of n-phosphonomethyl glycine |
US4721726A (en) * | 1980-12-18 | 1988-01-26 | Schering Corporation | Substituted dipeptides as inhibitors of enkephalinases |
CY1406A (en) * | 1980-12-18 | 1988-04-22 | Schering Corp | Substituted dipeptides, processes for their preparation and pharmaceutical compositions containing them and their use in the inhibition of enkephalinase |
FR2518088B1 (fr) * | 1981-12-16 | 1987-11-27 | Roques Bernard | Nouveaux derives d'aminoacides, et leur application therapeutique |
AU569719B2 (en) * | 1983-01-28 | 1988-02-18 | Schering Corporation | Phosphorous compounds as inhibitors of enkephalinases |
US4939261A (en) * | 1984-06-08 | 1990-07-03 | Ciba-Geigy Corporation | N-substituted butyramide derivatives useful for treatment of conditions responsive to inhibition of enkephalinase |
EP0225292A3 (en) * | 1985-12-06 | 1988-11-30 | Ciba-Geigy Ag | Certain n-substituted butyramide derivatives |
US4749688A (en) * | 1986-06-20 | 1988-06-07 | Schering Corporation | Use of neutral metalloendopeptidase inhibitors in the treatment of hypertension |
CA1337400C (en) * | 1987-06-08 | 1995-10-24 | Norma G. Delaney | Inhibitors of neutral endopeptidase |
US4963539A (en) * | 1987-09-10 | 1990-10-16 | E. R. Squibb & Sons, Inc. | Phosphonate and phosphonamide endopeptidase inhibitors |
GB8726714D0 (en) * | 1987-11-14 | 1987-12-16 | Beecham Group Plc | Compounds |
EP0401963A1 (en) * | 1989-04-13 | 1990-12-12 | Beecham Group p.l.c. | Phosphonopeptides with collagenase inhibiting activity |
FR2652087B1 (fr) * | 1989-09-15 | 1993-10-15 | Bioprojet Ste Civile | Derives d'amino-acides, leur procede de preparation et leurs applications therapeutiques. |
-
1991
- 1991-05-01 US US07/694,533 patent/US5155100A/en not_active Expired - Fee Related
-
1992
- 1992-04-17 IL IL10163392A patent/IL101633A/en not_active IP Right Cessation
- 1992-04-22 EP EP19920810291 patent/EP0511940A3/en not_active Ceased
- 1992-04-23 AU AU15091/92A patent/AU655252B2/en not_active Ceased
- 1992-04-27 JP JP4107296A patent/JPH05170792A/ja active Pending
- 1992-04-27 FI FI921884A patent/FI921884A/fi not_active Application Discontinuation
- 1992-04-28 MX MX9201953A patent/MX9201953A/es unknown
- 1992-04-29 NZ NZ242546A patent/NZ242546A/en unknown
- 1992-04-29 HU HU9201430A patent/HUT61032A/hu unknown
- 1992-04-29 CA CA002067592A patent/CA2067592A1/en not_active Abandoned
- 1992-04-30 NO NO92921719A patent/NO921719L/no unknown
- 1992-04-30 KR KR1019920007343A patent/KR920021578A/ko not_active Application Discontinuation
- 1992-04-30 ZA ZA923164A patent/ZA923164B/xx unknown
- 1992-05-19 TW TW081103890A patent/TW208704B/zh active
- 1992-07-01 IE IE140192A patent/IE921401A1/en not_active Application Discontinuation
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ZA923164B (en) | 1992-11-25 |
NZ242546A (en) | 1994-08-26 |
EP0511940A2 (en) | 1992-11-04 |
US5155100A (en) | 1992-10-13 |
HU9201430D0 (en) | 1992-07-28 |
IL101633A0 (en) | 1992-12-30 |
FI921884A (fi) | 1992-11-02 |
FI921884A0 (fi) | 1992-04-27 |
AU1509192A (en) | 1992-11-05 |
EP0511940A3 (en) | 1993-11-03 |
NO921719D0 (no) | 1992-04-30 |
TW208704B (xx) | 1993-07-01 |
HUT61032A (en) | 1992-11-30 |
IE921401A1 (en) | 1992-11-04 |
NO921719L (no) | 1992-11-02 |
MX9201953A (es) | 1992-11-01 |
KR920021578A (ko) | 1992-12-18 |
JPH05170792A (ja) | 1993-07-09 |
CA2067592A1 (en) | 1992-11-02 |
AU655252B2 (en) | 1994-12-08 |
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