ES2219762T3 - Bifenil isoxazolil sulfonamidas sustituidas. - Google Patents
Bifenil isoxazolil sulfonamidas sustituidas.Info
- Publication number
- ES2219762T3 ES2219762T3 ES97915055T ES97915055T ES2219762T3 ES 2219762 T3 ES2219762 T3 ES 2219762T3 ES 97915055 T ES97915055 T ES 97915055T ES 97915055 T ES97915055 T ES 97915055T ES 2219762 T3 ES2219762 T3 ES 2219762T3
- Authority
- ES
- Spain
- Prior art keywords
- dimethyl
- oxazolyl
- isoxazolyl
- biphenyl
- methyl
- 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.)
- Expired - Lifetime
Links
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- 150000003456 sulfonamides Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 349
- -1 cycloalkenylalkyl Chemical group 0.000 claims abstract description 201
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 59
- 125000003118 aryl group Chemical group 0.000 claims abstract description 30
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 23
- 239000001257 hydrogen Substances 0.000 claims abstract description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 21
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 20
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 19
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 17
- 125000004450 alkenylene group Chemical group 0.000 claims abstract description 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 13
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 13
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- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims abstract description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 10
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 9
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 9
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
- 239000002253 acid Substances 0.000 claims description 72
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 58
- 150000003839 salts Chemical class 0.000 claims description 42
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
- 238000011282 treatment Methods 0.000 claims description 39
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 35
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 31
- 235000010290 biphenyl Nutrition 0.000 claims description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
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- 125000005843 halogen group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
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- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical group 0.000 claims description 10
- SBXDENYROQKXBE-UHFFFAOYSA-N 2-phenylbenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1C1=CC=CC=C1 SBXDENYROQKXBE-UHFFFAOYSA-N 0.000 claims description 9
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- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 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 claims description 7
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- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 7
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
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- IJIMQIGNXVGSDW-UHFFFAOYSA-N 2-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)benzoic acid Chemical compound CC1=NOC(NS(=O)(=O)C=2C(=CC=CC=2)C=2C(=CC(=CC=2)C=2OC=CN=2)C(O)=O)=C1C IJIMQIGNXVGSDW-UHFFFAOYSA-N 0.000 claims description 4
- QUGYWVIGHQDGMZ-UHFFFAOYSA-N 3,4-dimethyl-5-[2-[3-(2-methylpropoxymethyl)-4-phenylphenyl]-2h-1,3-oxazol-3-yl]-1,2-oxazole Chemical compound CC(C)COCC1=CC(C2N(C=CO2)C2=C(C(C)=NO2)C)=CC=C1C1=CC=CC=C1 QUGYWVIGHQDGMZ-UHFFFAOYSA-N 0.000 claims description 4
- IOHFJLOGXVKAOM-UHFFFAOYSA-N 3,4-dimethyl-5-[2-[[5-(1,3-oxazol-2-yl)-2-phenylphenyl]methyl]-2H-1,3-oxazol-3-yl]-1,2-oxazole Chemical compound CC1=NOC(=C1C)N1C(OC=C1)CC1=C(C=CC(=C1)C=1OC=CN=1)C1=CC=CC=C1 IOHFJLOGXVKAOM-UHFFFAOYSA-N 0.000 claims description 4
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 4
- OGTMPFUUALINIA-UHFFFAOYSA-N CC1=NOC(=C1C)N1C(OC=C1)C1=C(C=CC(=C1)C=1OC=CN=1)C1=CC=CC=C1 Chemical compound CC1=NOC(=C1C)N1C(OC=C1)C1=C(C=CC(=C1)C=1OC=CN=1)C1=CC=CC=C1 OGTMPFUUALINIA-UHFFFAOYSA-N 0.000 claims description 4
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- UZHZLWTWVKBXPA-UHFFFAOYSA-N N-[[5-[3-(3,4-dimethyl-1,2-oxazol-5-yl)-2H-1,3-oxazol-2-yl]-2-phenylphenyl]methyl]-2,2,2-trifluoroethanamine Chemical compound CC1=NOC(=C1C)N1C(OC=C1)C1=CC(=C(C=C1)C1=CC=CC=C1)CNCC(F)(F)F UZHZLWTWVKBXPA-UHFFFAOYSA-N 0.000 claims description 4
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- 229930002534 steroid glycoside Natural products 0.000 claims description 4
- OFYXRJHKRXHKCX-UHFFFAOYSA-N 1-[[5-[3-(3,4-dimethyl-1,2-oxazol-5-yl)-2H-1,3-oxazol-2-yl]-2-phenylphenyl]methyl]-3,3-dimethylpyrrolidin-2-one Chemical compound CC1=NOC(=C1C)N1C(OC=C1)C1=CC(=C(C=C1)C1=CC=CC=C1)CN1C(C(CC1)(C)C)=O OFYXRJHKRXHKCX-UHFFFAOYSA-N 0.000 claims description 3
- USGSDZWGPOECAK-UHFFFAOYSA-N 2-[5-[3-(3,4-dimethyl-1,2-oxazol-5-yl)-2H-1,3-oxazol-2-yl]-2-phenylphenyl]acetonitrile Chemical compound C(#N)CC1=C(C=CC(=C1)C1OC=CN1C1=C(C(=NO1)C)C)C1=CC=CC=C1 USGSDZWGPOECAK-UHFFFAOYSA-N 0.000 claims description 3
- NHUAKBYOEOQWMK-UHFFFAOYSA-N 2-[5-[3-(3,4-dimethyl-1,2-oxazol-5-yl)-2H-1,3-oxazol-2-yl]-2-phenylphenyl]propan-2-ol Chemical compound CC1=NOC(=C1C)N1C(OC=C1)C1=CC(=C(C=C1)C1=CC=CC=C1)C(C)(C)O NHUAKBYOEOQWMK-UHFFFAOYSA-N 0.000 claims description 3
- XLXYCNANNDJFJP-UHFFFAOYSA-N 3,4-dimethyl-5-[2-[3-(2-methylpropylsulfonylmethyl)-4-phenylphenyl]-2H-1,3-oxazol-3-yl]-1,2-oxazole Chemical compound CC1=NOC(=C1C)N1C(OC=C1)C1=CC(=C(C=C1)C1=CC=CC=C1)CS(=O)(=O)CC(C)C XLXYCNANNDJFJP-UHFFFAOYSA-N 0.000 claims description 3
- SYIZJIXUYQRLBB-UHFFFAOYSA-N 3,4-dimethyl-5-[2-[3-(phenoxymethyl)-4-phenylphenyl]-2H-1,3-oxazol-3-yl]-1,2-oxazole Chemical compound CC1=NOC(=C1C)N1C(OC=C1)C1=CC(=C(C=C1)C1=CC=CC=C1)COC1=CC=CC=C1 SYIZJIXUYQRLBB-UHFFFAOYSA-N 0.000 claims description 3
- ZWOVJDPAUFBPTM-UHFFFAOYSA-N 3,4-dimethyl-5-[2-[4-phenyl-3-(2-propan-2-yl-1,3-oxazol-4-yl)phenyl]-2H-1,3-oxazol-3-yl]-1,2-oxazole Chemical compound CC1=NOC(=C1C)N1C(OC=C1)C1=CC(=C(C=C1)C1=CC=CC=C1)C=1N=C(OC=1)C(C)C ZWOVJDPAUFBPTM-UHFFFAOYSA-N 0.000 claims description 3
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- UBDLLYCOQZVOED-UHFFFAOYSA-N 3,4-dimethyl-5-[5-methyl-2-(4-phenylphenyl)-2H-1,3-oxazol-3-yl]-1,2-oxazole Chemical compound CC1=NOC(=C1C)N1C(OC(=C1)C)C1=CC=C(C=C1)C1=CC=CC=C1 UBDLLYCOQZVOED-UHFFFAOYSA-N 0.000 claims description 3
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- BPRJCJVCGXSMEB-UHFFFAOYSA-N n-[[2-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-n-methyl-1,3-benzodioxole-5-carboxamide Chemical compound C=1C=C2OCOC2=CC=1C(=O)N(C)CC1=CC(C=2OC=CN=2)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C BPRJCJVCGXSMEB-UHFFFAOYSA-N 0.000 claims 1
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- WZSYJAUQVWBRAC-UHFFFAOYSA-N n-[[2-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-n-methyl-2-(2,4,6-trimethylphenyl)acetamide Chemical compound CC=1C=C(C)C=C(C)C=1CC(=O)N(C)CC1=CC(C=2OC=CN=2)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C WZSYJAUQVWBRAC-UHFFFAOYSA-N 0.000 claims 1
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- YRQIVEIVRAWSIB-UHFFFAOYSA-N n-[[2-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-n-methyl-2-pyridin-2-ylacetamide Chemical compound C=1C=CC=NC=1CC(=O)N(C)CC1=CC(C=2OC=CN=2)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C YRQIVEIVRAWSIB-UHFFFAOYSA-N 0.000 claims 1
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- MKIQWEDQDMTJMS-UHFFFAOYSA-N n-[[2-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-n-methyl-4-phenylbutanamide Chemical compound C=1C=CC=CC=1CCCC(=O)N(C)CC1=CC(C=2OC=CN=2)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C MKIQWEDQDMTJMS-UHFFFAOYSA-N 0.000 claims 1
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- CAPYHDUFQNQXNZ-UHFFFAOYSA-N n-[[2-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-n-methylnaphthalene-1-carboxamide Chemical compound C=1C=CC2=CC=CC=C2C=1C(=O)N(C)CC1=CC(C=2OC=CN=2)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C CAPYHDUFQNQXNZ-UHFFFAOYSA-N 0.000 claims 1
- WXYCKWKKERRICY-UHFFFAOYSA-N n-[[2-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-n-methyloxolane-2-carboxamide Chemical compound C1CCOC1C(=O)N(C)CC1=CC(C=2OC=CN=2)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C WXYCKWKKERRICY-UHFFFAOYSA-N 0.000 claims 1
- LDUHHKKKMDLMKC-UHFFFAOYSA-N n-[[2-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-n-methylpyrazine-2-carboxamide Chemical compound C=1N=CC=NC=1C(=O)N(C)CC1=CC(C=2OC=CN=2)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C LDUHHKKKMDLMKC-UHFFFAOYSA-N 0.000 claims 1
- NPVXQIZTHBJVMG-UHFFFAOYSA-N n-[[2-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-n-methylpyridine-2-carboxamide Chemical compound C=1C=CC=NC=1C(=O)N(C)CC1=CC(C=2OC=CN=2)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C NPVXQIZTHBJVMG-UHFFFAOYSA-N 0.000 claims 1
- VXTCEHYJEGIMBC-UHFFFAOYSA-N n-[[2-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-n-methylpyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)N(C)CC1=CC(C=2OC=CN=2)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C VXTCEHYJEGIMBC-UHFFFAOYSA-N 0.000 claims 1
- SWEWDMZULVGCQX-UHFFFAOYSA-N n-[[2-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-n-methylpyridine-4-carboxamide Chemical compound C=1C=NC=CC=1C(=O)N(C)CC1=CC(C=2OC=CN=2)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C SWEWDMZULVGCQX-UHFFFAOYSA-N 0.000 claims 1
- YNJMUZRZFZRORD-UHFFFAOYSA-N n-[[2-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-n-methylthiadiazole-4-carboxamide Chemical compound C=1SN=NC=1C(=O)N(C)CC1=CC(C=2OC=CN=2)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C YNJMUZRZFZRORD-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
- C07D231/42—Benzene-sulfonamido pyrazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US60397596A | 1996-02-20 | 1996-02-20 | |
| US603975 | 1996-02-20 | ||
| US75471596A | 1996-11-21 | 1996-11-21 | |
| US754715 | 1996-11-21 | ||
| US799616 | 1997-02-13 | ||
| US08/799,616 US5846990A (en) | 1995-07-24 | 1997-02-13 | Substituted biphenyl isoxazole sulfonamides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2219762T3 true ES2219762T3 (es) | 2004-12-01 |
Family
ID=27416891
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES97915055T Expired - Lifetime ES2219762T3 (es) | 1996-02-20 | 1997-02-20 | Bifenil isoxazolil sulfonamidas sustituidas. |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US5846990A (https=) |
| EP (1) | EP0921800B1 (https=) |
| JP (1) | JP2002500619A (https=) |
| AT (1) | ATE264324T1 (https=) |
| AU (1) | AU720458B2 (https=) |
| CA (1) | CA2240043A1 (https=) |
| DE (1) | DE69728673T2 (https=) |
| ES (1) | ES2219762T3 (https=) |
| WO (1) | WO1997029748A1 (https=) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6541498B2 (en) | 1993-05-20 | 2003-04-01 | Texas Biotechnology | Benzenesulfonamides and the use thereof to modulate the activity of endothelin |
| JPH09124620A (ja) | 1995-10-11 | 1997-05-13 | Bristol Myers Squibb Co | 置換ビフェニルスルホンアミドエンドセリン拮抗剤 |
| EP0904077A4 (en) * | 1996-02-20 | 1999-12-22 | Bristol Myers Squibb Co | PROCESSES FOR THE PRODUCTION OF BIPHENYL ISOXAZOLE SULFAMIDES |
| TW536540B (en) * | 1997-01-30 | 2003-06-11 | Bristol Myers Squibb Co | Endothelin antagonists: N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide and N-(4,5-dimethyl-3-isoxazolyl)-2'-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4'-(2-oxazolyl)[1,1'-biphe |
| AP9901643A0 (en) | 1997-04-28 | 1999-10-02 | Texas Biotechnology Corp | Sulfonamides for treatment of endothelin-mediated disorders. |
| AU742506B2 (en) * | 1997-10-17 | 2002-01-03 | Eurogene Limited | The use of inhibitors of the renin-angiotensin system |
| DE19813354A1 (de) * | 1998-03-26 | 1999-09-30 | Bayer Ag | Arylphenylsubstituierte cyclische Ketoenole |
| US6638937B2 (en) | 1998-07-06 | 2003-10-28 | Bristol-Myers Squibb Co. | Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists |
| WO2000001389A1 (en) * | 1998-07-06 | 2000-01-13 | Bristol-Myers Squibb Co. | Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists |
| TW526202B (en) | 1998-11-27 | 2003-04-01 | Shionogi & Amp Co | Broad spectrum cephem having benzo[4,5-b]pyridium methyl group of antibiotic activity |
| IL144708A0 (en) * | 1999-03-19 | 2002-06-30 | Bristol Myers Squibb Co | Methods for the preparation of biphenyl isoxazole sulfonamide derivatives |
| DE60030764T2 (de) * | 1999-12-15 | 2007-09-13 | Bristol-Myers Squibb Co. | Biphenyl - sulfonamide als duale angiotensin - endothelin - rezeptor - antagonisten |
| HUP0203935A3 (en) | 1999-12-31 | 2006-02-28 | Encysive Pharmaceuticals Inc H | Sulfonamides and derivatives thereof that modulate the activity of endothelin, pharmaceutical compositions containing them and their use |
| JP2004501083A (ja) | 2000-04-18 | 2004-01-15 | アゴーロン・ファーマシューティカルズ・インコーポレイテッド | プロテインキナーゼを阻害するためのピラゾール |
| US6639082B2 (en) | 2000-10-17 | 2003-10-28 | Bristol-Myers Squibb Company | Methods for the preparation of biphenyl isoxazole sulfonamides |
| US8168616B1 (en) | 2000-11-17 | 2012-05-01 | Novartis Ag | Combination comprising a renin inhibitor and an angiotensin receptor inhibitor for hypertension |
| CA2438868A1 (en) * | 2001-02-20 | 2002-09-19 | Valentin K. Gribkoff | Modulators of kcnq potassium channels and use thereof in treating migraine and mechanistically related diseases |
| WO2003055482A1 (en) * | 2001-12-21 | 2003-07-10 | Novo Nordisk A/S | Amide derivatives as gk activators |
| US7338969B2 (en) | 2002-03-08 | 2008-03-04 | Quonova, Llc | Modulation of pathogenicity |
| US7335779B2 (en) * | 2002-03-08 | 2008-02-26 | Quonova, Llc | Modulation of pathogenicity |
| BR0312023A (pt) * | 2002-06-27 | 2005-03-22 | Novo Nordisk As | Composto, composto ativador da glicose cinase, método para evitar a hipoglicemia, uso de um composto, e, composição farmacêutica |
| EP1551403B1 (en) * | 2002-10-10 | 2009-04-29 | Arena Pharmaceuticals, Inc. | 5-substituted 2h-pyrazone-3-carboxylic acid derivatives as antilipolytic agents for the treatment of metabolic-related disorders such as dyslipidemia |
| GB0225548D0 (en) | 2002-11-01 | 2002-12-11 | Glaxo Group Ltd | Compounds |
| US7273866B2 (en) * | 2002-12-20 | 2007-09-25 | Bristol-Myers Squibb Company | 2-aryl thiazole derivatives as KCNQ modulators |
| US6933308B2 (en) * | 2002-12-20 | 2005-08-23 | Bristol-Myers Squibb Company | Aminoalkyl thiazole derivatives as KCNQ modulators |
| US20070197492A1 (en) * | 2003-05-06 | 2007-08-23 | Aldo Ammendola | Modulation of Pathogenicity |
| CA2528834A1 (en) * | 2003-06-13 | 2005-02-10 | Arena Pharmaceuticals, Inc. | 5-substituted 2h-pyrazole-3-carboxylic acid derivatives as agonists for the nicotinic acid receptor rup25 for the treatment of dyslipidemia and related diseases |
| BRPI0412003A (pt) * | 2003-07-02 | 2006-08-15 | Sugen Inc | arilmetil triazol e imidazopirazinas como inibidores de c-met |
| DE10337497A1 (de) | 2003-08-14 | 2005-03-10 | Bayer Cropscience Ag | 4-Biphenylsubstituierte-Pyrazolidin-3,5-dion-Derivate |
| JP4834840B2 (ja) * | 2004-01-06 | 2011-12-14 | ノヴォ ノルディスク アー/エス | ヘテロアリール尿素およびグルコキナーゼ活性化剤としてのその使用 |
| US7854924B2 (en) * | 2004-03-30 | 2010-12-21 | Relypsa, Inc. | Methods and compositions for treatment of ion imbalances |
| BRPI0509331B8 (pt) * | 2004-03-30 | 2021-05-25 | Ilypsa Inc | uso de uma composição de ligação de sódio |
| ES2282062T1 (es) | 2004-06-04 | 2007-10-16 | Teva Pharmaceutical Industries Ltd. | Composicion farmaceutica que contiene irbesartan. |
| DOP2005000123A (es) * | 2004-07-02 | 2011-07-15 | Merck Sharp & Dohme | Inhibidores de cetp |
| FR2874015B1 (fr) * | 2004-08-05 | 2006-09-15 | Sanofi Synthelabo | Derives de n-(1h-indolyl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
| FR2880625B1 (fr) * | 2005-01-07 | 2007-03-09 | Sanofi Aventis Sa | Derives de n-(heteroaryl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
| ES2382815T3 (es) * | 2005-07-08 | 2012-06-13 | Novo Nordisk A/S | Dicicloalquilcarbamoil ureas como activadores de glucoquinasa |
| US7582769B2 (en) * | 2005-07-08 | 2009-09-01 | Novo Nordisk A/S | Dicycloalkyl urea glucokinase activators |
| US7884210B2 (en) | 2005-07-14 | 2011-02-08 | Novo Nordisk A/S | Ureido-thiazole glucokinase activators |
| CA2624112A1 (en) * | 2005-09-30 | 2007-04-05 | Ilypsa, Inc. | Methods for preparing core-shell composites having cross-linked shells and core-shell composites resulting therefrom |
| GB2446077B (en) | 2005-09-30 | 2010-10-13 | Ilypsa Inc | Methods and compositions for selectively removing potassium ion from the gastrointestinal tract of a mammal |
| MX2008011227A (es) * | 2006-03-03 | 2009-02-10 | Torrent Pharmaceuticals Ltd | Receptores antagonistas de accion nueva y doble en los receptores at1 y eta. |
| WO2008084043A1 (en) * | 2007-01-09 | 2008-07-17 | Novo Nordisk A/S | Urea glucokinase activators |
| WO2008084044A1 (en) | 2007-01-11 | 2008-07-17 | Novo Nordisk A/S | Urea glucokinase activators |
| UY30892A1 (es) * | 2007-02-07 | 2008-09-02 | Smithkline Beckman Corp | Inhibidores de la actividad akt |
| MX389664B (es) * | 2008-08-22 | 2025-03-20 | Vifor Int Ltd | Polimeros reticulados de intercambio cationico, composiciones y su uso en el tratamiento de la hipercalcemia |
| US8337824B2 (en) | 2008-08-22 | 2012-12-25 | Relypsa, Inc. | Linear polyol stabilized polyfluoroacrylate compositions |
| US20100104527A1 (en) * | 2008-08-22 | 2010-04-29 | Relypsa, Inc. | Treating hyperkalemia with crosslinked cation exchange polymers of improved physical properties |
| US20140057953A1 (en) * | 2011-03-03 | 2014-02-27 | Rolf Hartmann | Biaryl derivatives as selective 17beta-hydroxysteroid dehydrogenase type 2 inhibitors |
| JP6475624B2 (ja) | 2012-10-08 | 2019-02-27 | レリプサ, インコーポレイテッド | 高血圧症及び高カリウム血症を治療するためのカリウム結合剤 |
| CN112040945A (zh) | 2018-06-12 | 2020-12-04 | Vtv治疗有限责任公司 | 葡萄糖激酶激活剂与胰岛素或胰岛素类似物组合的治疗用途 |
| US12391658B2 (en) | 2020-02-18 | 2025-08-19 | Vtv Therapeutics Llc | Sulfoxide and sulfone glucokinase activators and methods of use thereof |
| MX2024000518A (es) * | 2021-07-09 | 2024-01-31 | Vicore Pharma Ab | Nuevos compuestos selectivos de angiotensina ii. |
| WO2023224963A1 (en) * | 2022-05-16 | 2023-11-23 | Aria Pharmaceuticals, Inc. | Dual-acting angiotensin and endothelin receptor antagonists |
| CN115010621B (zh) * | 2022-07-21 | 2023-11-03 | 山东百启生物医药有限公司 | 一种4-溴-3-甲基苯甲腈的合成方法 |
| CN115677511B (zh) * | 2022-10-26 | 2024-06-21 | 南通华祥医药科技有限公司 | 一种2,2-二氟丙胺盐酸盐的合成方法 |
Family Cites Families (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB804036A (en) * | 1956-03-02 | 1958-11-05 | Hoffmann La Roche | A process for the manufacture of a sulphanilamide of the isoxazole series |
| DE1059459B (de) * | 1956-09-04 | 1959-06-18 | Shionogi & Co | Verfahren zur Herstellung des therapeutisch wertvollen 3-Sulfanilamido-5-methylisoxazols |
| US2888455A (en) * | 1956-09-04 | 1959-05-26 | Shionogi & Co | New sulfonamide and process for producing the same |
| CH364506A (de) * | 1956-09-04 | 1962-09-30 | Shionogi & Co | Verfahren zur Herstellung des therapeutisch wirksamen 3-Sulfanilamido-5-methyl-isoxazols |
| GB897440A (en) * | 1960-02-08 | 1962-05-30 | Shionogi & Co | Improvements in or relating to sulfonamides |
| GB1473433A (https=) * | 1975-10-09 | 1977-05-11 | Banyu Pharmaceutical Co Ltd Hi | |
| US4415496A (en) * | 1981-03-23 | 1983-11-15 | Merck & Co., Inc. | Bicyclic lactams |
| EP0076072B1 (en) * | 1981-09-24 | 1987-05-13 | BEECHAM - WUELFING GmbH & Co. KG | Sulphonamides |
| US4661479A (en) * | 1982-02-19 | 1987-04-28 | Merck And Co., Inc. | Bicyclic lactams as antihypertensives |
| EP0194548A3 (de) * | 1985-03-12 | 1988-08-17 | Dr. Karl Thomae GmbH | Neue Sulfonylaminoäthylverbindungen, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| US5464853A (en) * | 1993-05-20 | 1995-11-07 | Immunopharmaceutics, Inc. | N-(5-isoxazolyl)biphenylsulfonamides, N-(3-isoxazolyl)biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin |
| US5591761A (en) * | 1993-05-20 | 1997-01-07 | Texas Biotechnology Corporation | Thiophenyl-, furyl-and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin |
| US5594021A (en) * | 1993-05-20 | 1997-01-14 | Texas Biotechnology Corporation | Thienyl-, furyl- and pyrrolyl sulfonamides and derivatives thereof that modulate the activity of endothelin |
| US5514691A (en) * | 1993-05-20 | 1996-05-07 | Immunopharmaceutics, Inc. | N-(4-halo-isoxazolyl)-sulfonamides and derivatives thereof that modulate the activity of endothelin |
| US5571821A (en) * | 1993-05-20 | 1996-11-05 | Texas Biotechnology Corporation | Sulfonamides and derivatives thereof that modulate the activity of endothelin |
| CA2005741C (en) * | 1988-12-26 | 1998-06-02 | Hiroyoshi Hidaka | Quinoline sulfonoamino compounds having vessel smooth muscle relaxation activity |
| US5082838A (en) * | 1989-06-21 | 1992-01-21 | Takeda Chemical Industries, Ltd. | Sulfur-containing fused pyrimidine derivatives, their production and use |
| IL97219A (en) * | 1990-02-19 | 1995-12-08 | Ciba Geigy Ag | Biphenyl substituted aliphatic amino compounds process for their preparation and pharmaceutical compositions containing them |
| CA2079343A1 (en) * | 1990-03-30 | 1991-10-01 | Eric E. Allen | Substituted pyrazoles, isoxazoles and isothiazoles |
| US5236928A (en) * | 1991-03-19 | 1993-08-17 | Merck & Co., Inc. | Imidazole derivatives bearing acidic functional groups at the 5-position, their compositions and methods of use as angiotensin II antagonists |
| TW270116B (https=) * | 1991-04-25 | 1996-02-11 | Hoffmann La Roche | |
| RU2086544C1 (ru) * | 1991-06-13 | 1997-08-10 | Хоффманн-Ля Рош АГ | Бензолсульфонамидные производные пиримидина или их соли, фармацевтическая композиция для лечения заболеваний, связанных с активностью эндотелина |
| UA44686C2 (uk) * | 1991-11-05 | 2002-03-15 | Смітклайн Бічем Корпорейшн | Похідні індану або індену як антагоністи ендотелінових рецепторів, фармацевтична композиція на їх основі, спосіб їх одержання та спосіб пригнічення ендотелінових рецепторів |
| SE9103397D0 (sv) * | 1991-11-18 | 1991-11-18 | Kabi Pharmacia Ab | Nya substituerade salicylsyror |
| TW224462B (https=) * | 1992-02-24 | 1994-06-01 | Squibb & Sons Inc | |
| US5378715A (en) * | 1992-02-24 | 1995-01-03 | Bristol-Myers Squibb Co. | Sulfonamide endothelin antagonists |
| TW215434B (https=) * | 1992-03-07 | 1993-11-01 | Hoechst Ag | |
| NZ247440A (en) * | 1992-05-06 | 1995-04-27 | Squibb & Sons Inc | Phenyl sulphonamide derivatives, preparation and pharmaceutical compositions thereof |
| US5514696A (en) * | 1992-05-06 | 1996-05-07 | Bristol-Myers Squibb Co. | Phenyl sulfonamide endothelin antagonists |
| WO1993023404A1 (en) * | 1992-05-19 | 1993-11-25 | Immunopharmaceutics, Inc. | Compounds that modulate endothelin activity |
| TW287160B (https=) * | 1992-12-10 | 1996-10-01 | Hoffmann La Roche | |
| EP0617001B1 (en) * | 1993-03-19 | 2000-01-26 | Merck & Co. Inc. | Phenoxyphenylacetic acid derivatives |
| CA2121724A1 (en) * | 1993-04-21 | 1994-10-22 | Toshifumi Watanabe | Methods and compositions for the prophylactic and/or therapeutic treatment of organ hypofunction |
| TW394761B (en) * | 1993-06-28 | 2000-06-21 | Hoffmann La Roche | Novel Sulfonylamino Pyrimidines |
| DK0634175T3 (da) * | 1993-07-15 | 2001-04-30 | Hoffmann La Roche | Farmaceutisk kombination, der indeholder en hæmmer af renin-angiotensin-systemet og en endothelin-antagonist |
| US5965732A (en) * | 1993-08-30 | 1999-10-12 | Bristol-Myers Squibb Co. | Sulfonamide endothelin antagonists |
| GB9504854D0 (en) * | 1994-03-31 | 1995-04-26 | Zeneca Ltd | Nitrogen derivatives |
| GB9409618D0 (en) * | 1994-05-13 | 1994-07-06 | Zeneca Ltd | Pyridine derivatives |
| US5612359A (en) * | 1994-08-26 | 1997-03-18 | Bristol-Myers Squibb Company | Substituted biphenyl isoxazole sulfonamides |
| CA2168154A1 (en) * | 1995-02-06 | 1996-08-07 | Natesan Murugesan | Substituted biphenyl sulfonamide endothelin antagonists |
| DE19509950A1 (de) * | 1995-03-18 | 1996-09-19 | Merck Patent Gmbh | Endothelin-Rezeptor-Antagonisten |
| HUP9802034A3 (en) * | 1995-04-04 | 2000-04-28 | Encysive Pharmaceuticals Inc H | Thienyl-, furyl-, pyrrolyl- and biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin and use of the compounds |
| UA58494C2 (uk) * | 1995-06-07 | 2003-08-15 | Зенека Лімітед | Похідні n-гетероарилпіридинсульфонаміду, фармацевтична композиція, спосіб одержання та спосіб протидії впливам ендотеліну |
| GB9512697D0 (en) * | 1995-06-22 | 1995-08-23 | Zeneca Ltd | Heterocyclic compounds |
| EP0904077A4 (en) * | 1996-02-20 | 1999-12-22 | Bristol Myers Squibb Co | PROCESSES FOR THE PRODUCTION OF BIPHENYL ISOXAZOLE SULFAMIDES |
| TW536540B (en) * | 1997-01-30 | 2003-06-11 | Bristol Myers Squibb Co | Endothelin antagonists: N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide and N-(4,5-dimethyl-3-isoxazolyl)-2'-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4'-(2-oxazolyl)[1,1'-biphe |
-
1997
- 1997-02-13 US US08/799,616 patent/US5846990A/en not_active Expired - Lifetime
- 1997-02-20 DE DE69728673T patent/DE69728673T2/de not_active Expired - Fee Related
- 1997-02-20 EP EP97915055A patent/EP0921800B1/en not_active Expired - Lifetime
- 1997-02-20 WO PCT/US1997/003956 patent/WO1997029748A1/en not_active Ceased
- 1997-02-20 ES ES97915055T patent/ES2219762T3/es not_active Expired - Lifetime
- 1997-02-20 JP JP52962097A patent/JP2002500619A/ja not_active Ceased
- 1997-02-20 AT AT97915055T patent/ATE264324T1/de not_active IP Right Cessation
- 1997-02-20 CA CA002240043A patent/CA2240043A1/en not_active Abandoned
- 1997-02-20 AU AU22098/97A patent/AU720458B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP0921800B1 (en) | 2004-04-14 |
| AU720458B2 (en) | 2000-06-01 |
| JP2002500619A (ja) | 2002-01-08 |
| ATE264324T1 (de) | 2004-04-15 |
| WO1997029748A1 (en) | 1997-08-21 |
| EP0921800A4 (en) | 2000-12-06 |
| DE69728673T2 (de) | 2005-03-31 |
| DE69728673D1 (de) | 2004-05-19 |
| EP0921800A1 (en) | 1999-06-16 |
| US5846990A (en) | 1998-12-08 |
| AU2209897A (en) | 1997-09-02 |
| CA2240043A1 (en) | 1997-08-21 |
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