AU655252B2 - Phosphono/biaryl substituted dipeptide derivatives - Google Patents
Phosphono/biaryl substituted dipeptide derivatives Download PDFInfo
- Publication number
- AU655252B2 AU655252B2 AU15091/92A AU1509192A AU655252B2 AU 655252 B2 AU655252 B2 AU 655252B2 AU 15091/92 A AU15091/92 A AU 15091/92A AU 1509192 A AU1509192 A AU 1509192A AU 655252 B2 AU655252 B2 AU 655252B2
- Authority
- AU
- Australia
- Prior art keywords
- pharmaceutically acceptable
- propionyl
- acceptable salt
- biphenylyl
- phosphonomethylamino
- Prior art date
- Legal status (The legal status 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 status listed.)
- Ceased
Links
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 title claims description 15
- 108010016626 Dipeptides Proteins 0.000 title claims description 6
- 125000005841 biaryl group Chemical group 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims description 167
- 150000001875 compounds Chemical class 0.000 claims description 165
- -1 6-tetrahydronaphthyl Chemical group 0.000 claims description 160
- 125000000217 alkyl group Chemical group 0.000 claims description 134
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 84
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 77
- 238000000034 method Methods 0.000 claims description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims description 45
- 239000001257 hydrogen Substances 0.000 claims description 45
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 42
- 239000002253 acid Substances 0.000 claims description 41
- 150000002148 esters Chemical class 0.000 claims description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 37
- 239000000203 mixture Substances 0.000 claims description 36
- 125000003545 alkoxy group Chemical group 0.000 claims description 32
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 150000002367 halogens Chemical class 0.000 claims description 30
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 21
- 229910052701 rubidium Inorganic materials 0.000 claims description 20
- 239000011734 sodium Substances 0.000 claims description 20
- 102000003729 Neprilysin Human genes 0.000 claims description 19
- 108090000028 Neprilysin Proteins 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 19
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 150000001408 amides Chemical class 0.000 claims description 17
- 230000008569 process Effects 0.000 claims description 17
- 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 16
- 125000004423 acyloxy group Chemical group 0.000 claims description 16
- 125000002541 furyl group Chemical group 0.000 claims description 15
- 229910052708 sodium Inorganic materials 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 14
- 229910052705 radium Inorganic materials 0.000 claims description 14
- 125000001544 thienyl group Chemical group 0.000 claims description 14
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 239000012044 organic layer Substances 0.000 claims description 13
- 125000002947 alkylene group Chemical group 0.000 claims description 12
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 11
- 125000002837 carbocyclic group Chemical group 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
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 8
- 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
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 230000003287 optical effect Effects 0.000 claims description 8
- 229940086681 4-aminobenzoate Drugs 0.000 claims description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 230000005764 inhibitory process 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
- 125000004457 alkyl amino carbonyl group Chemical group 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
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
- 239000000969 carrier Substances 0.000 claims description 5
- 125000004956 cyclohexylene 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
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 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
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- PEHSSTUGJUBZBI-UHFFFAOYSA-N indan-5-ol Chemical compound OC1=CC=C2CCCC2=C1 PEHSSTUGJUBZBI-UHFFFAOYSA-N 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 4
- RQKYHDHLEMEVDR-UHFFFAOYSA-N oxo-bis(phenylmethoxy)phosphanium Chemical compound C=1C=CC=CC=1CO[P+](=O)OCC1=CC=CC=C1 RQKYHDHLEMEVDR-UHFFFAOYSA-N 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 239000004305 biphenyl Substances 0.000 claims description 3
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 3
- GTTBQSNGUYHPNK-UHFFFAOYSA-N hydroxymethylphosphonic acid Chemical class OCP(O)(O)=O GTTBQSNGUYHPNK-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 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
- 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 description 2
- KFHKPFNUGLOSDB-LJAQVGFWSA-N 3-[[(2s)-3-[4-(4-chlorophenyl)phenyl]-2-(diphenoxyphosphorylmethylamino)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=C(Cl)C=C1 KFHKPFNUGLOSDB-LJAQVGFWSA-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
- OJBIOWNYEISPBN-UMSFTDKQSA-N [2-(diethylamino)-2-oxoethyl] 3-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]propanoate Chemical compound C([C@@H](C(=O)NCCC(=O)OCC(=O)N(CC)CC)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 OJBIOWNYEISPBN-UMSFTDKQSA-N 0.000 claims description 2
- YGYLYUIRSJSFJS-QMMMGPOBSA-N benzyl (2s)-2-aminopropanoate Chemical compound C[C@H](N)C(=O)OCC1=CC=CC=C1 YGYLYUIRSJSFJS-QMMMGPOBSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000002452 interceptive effect Effects 0.000 claims description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims 2
- 239000004471 Glycine Substances 0.000 claims 2
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- OLYNYZIEGHUIJI-HKBQPEDESA-N 3-[[(2s)-2-[bis(3-methoxyphenoxy)phosphorylmethylamino]-3-(4-phenylphenyl)propanoyl]amino]propanoic acid Chemical compound COC1=CC=CC(OP(=O)(CN[C@@H](CC=2C=CC(=CC=2)C=2C=CC=CC=2)C(=O)NCCC(O)=O)OC=2C=C(OC)C=CC=2)=C1 OLYNYZIEGHUIJI-HKBQPEDESA-N 0.000 claims 1
- SUDHZUVTDLPZRS-UHFFFAOYSA-N 3-[[3-(4-phenylphenyl)-2-(phosphonomethylamino)propanoyl]amino]propanoic acid;hydrobromide Chemical compound Br.C1=CC(CC(C(=O)NCCC(=O)O)NCP(O)(O)=O)=CC=C1C1=CC=CC=C1 SUDHZUVTDLPZRS-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- IYBXNSMBKTWFHQ-NXFUPXHFSA-N 4-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]cyclohexane-1-carboxylic acid Chemical compound C1CC(C(=O)O)CCC1NC(=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 IYBXNSMBKTWFHQ-NXFUPXHFSA-N 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- MEZULCFJPPZDTE-XIFFEERXSA-N 7-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]heptanoic acid Chemical compound C([C@@H](C(=O)NCCCCCCC(=O)O)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 MEZULCFJPPZDTE-XIFFEERXSA-N 0.000 claims 1
- 101150062005 CDK20 gene Proteins 0.000 claims 1
- 101100447646 Caenorhabditis elegans gars-1 gene Proteins 0.000 claims 1
- PBINYKMGYKHAQL-UHFFFAOYSA-N [[1-oxo-1-[[3-oxo-3-(pyridin-3-ylmethoxy)propyl]amino]-3-(4-phenylphenyl)propan-2-yl]amino]methylphosphonic acid;hydrochloride Chemical compound Cl.C=1C=CN=CC=1COC(=O)CCNC(=O)C(NCP(O)(=O)O)CC(C=C1)=CC=C1C1=CC=CC=C1 PBINYKMGYKHAQL-UHFFFAOYSA-N 0.000 claims 1
- 229960004050 aminobenzoic acid Drugs 0.000 claims 1
- 229960005190 phenylalanine Drugs 0.000 claims 1
- 235000013350 formula milk Nutrition 0.000 description 103
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 87
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 45
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 235000019439 ethyl acetate Nutrition 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 29
- 229940093499 ethyl acetate Drugs 0.000 description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- 239000007858 starting material Substances 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 150000002431 hydrogen Chemical class 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
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- 239000002585 base Substances 0.000 description 18
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- 235000015424 sodium Nutrition 0.000 description 14
- 150000007513 acids Chemical class 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 12
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
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- 206010020772 Hypertension Diseases 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
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- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
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- 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 description 5
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- 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
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
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- 230000002883 vasorelaxation effect Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
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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)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/694,533 US5155100A (en) | 1991-05-01 | 1991-05-01 | Phosphono/biaryl substituted dipeptide derivatives |
| US694533 | 1991-05-01 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU1509192A AU1509192A (en) | 1992-11-05 |
| AU655252B2 true AU655252B2 (en) | 1994-12-08 |
Family
ID=24789228
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU15091/92A Ceased AU655252B2 (en) | 1991-05-01 | 1992-04-23 | Phosphono/biaryl substituted dipeptide derivatives |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US5155100A (forum.php) |
| EP (1) | EP0511940A3 (forum.php) |
| JP (1) | JPH05170792A (forum.php) |
| KR (1) | KR920021578A (forum.php) |
| AU (1) | AU655252B2 (forum.php) |
| CA (1) | CA2067592A1 (forum.php) |
| FI (1) | FI921884A7 (forum.php) |
| HU (1) | HUT61032A (forum.php) |
| IE (1) | IE921401A1 (forum.php) |
| IL (1) | IL101633A (forum.php) |
| MX (1) | MX9201953A (forum.php) |
| NO (1) | NO921719L (forum.php) |
| NZ (1) | NZ242546A (forum.php) |
| TW (1) | TW208704B (forum.php) |
| ZA (1) | ZA923164B (forum.php) |
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| JPH05148277A (ja) * | 1991-11-05 | 1993-06-15 | Banyu Pharmaceut Co Ltd | アミノホスホン酸誘導体 |
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| 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 |
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| CN113166204B (zh) | 2018-11-27 | 2025-01-28 | 诺华股份有限公司 | 作为治疗代谢障碍的蛋白质原转换酶枯草杆菌蛋白酶/kexin 9型（PCSK9）抑制剂的环状肽 |
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| AU609900B2 (en) * | 1987-11-14 | 1991-05-09 | Beecham Group Plc | Amino acid derivatives of phosphorus acids |
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| US4721726A (en) * | 1980-12-18 | 1988-01-26 | Schering Corporation | Substituted dipeptides as inhibitors of enkephalinases |
| 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 |
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| EP0225292A3 (en) * | 1985-12-06 | 1988-11-30 | Ciba-Geigy Ag | Certain n-substituted butyramide derivatives |
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1991
- 1991-05-01 US US07/694,533 patent/US5155100A/en not_active Expired - Fee Related
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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/FI921884A7/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 ZA ZA923164A patent/ZA923164B/xx unknown
- 1992-04-30 NO NO92921719A patent/NO921719L/no unknown
- 1992-04-30 KR KR1019920007343A patent/KR920021578A/ko not_active Ceased
- 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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| AU609900B2 (en) * | 1987-11-14 | 1991-05-09 | Beecham Group Plc | Amino acid derivatives of phosphorus acids |
| EP0401963A1 (en) * | 1989-04-13 | 1990-12-12 | Beecham Group p.l.c. | Phosphonopeptides with collagenase inhibiting activity |
| AU618669B2 (en) * | 1989-04-13 | 1992-01-02 | Beecham Group Plc | Novel substituted phosphonic acids and esters |
Also Published As
| Publication number | Publication date |
|---|---|
| US5155100A (en) | 1992-10-13 |
| JPH05170792A (ja) | 1993-07-09 |
| ZA923164B (en) | 1992-11-25 |
| NO921719L (no) | 1992-11-02 |
| CA2067592A1 (en) | 1992-11-02 |
| HU9201430D0 (en) | 1992-07-28 |
| NO921719D0 (no) | 1992-04-30 |
| KR920021578A (ko) | 1992-12-18 |
| IL101633A (en) | 1996-03-31 |
| NZ242546A (en) | 1994-08-26 |
| IE921401A1 (en) | 1992-11-04 |
| EP0511940A2 (en) | 1992-11-04 |
| FI921884A0 (fi) | 1992-04-27 |
| EP0511940A3 (en) | 1993-11-03 |
| FI921884A7 (fi) | 1992-11-02 |
| TW208704B (forum.php) | 1993-07-01 |
| MX9201953A (es) | 1992-11-01 |
| AU1509192A (en) | 1992-11-05 |
| IL101633A0 (en) | 1992-12-30 |
| HUT61032A (en) | 1992-11-30 |
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