US 5,691,373 AGranted

Nonpeptide endothelin antagonists I

AssigneeWarner-Lambert Company

InventorsKent Alan Berryman, Annette Marian Doherty, Jeremy John Edmunds, William Chester Patt, Mark Stephen Plummer, Joseph Thomas Repine

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Abstract

Novel nonpeptide antagonists of endothelin I are described, as well as methods for the preparation and pharmaceutical compositions of the same, which are useful in treating elevated levels of endothelin, acute and chronic renal failure, hypertension, myocardial infarction, myocardial ischemia, cerebral vasospasm, cerebral ischemia, cerebral infarction, cirrhosis, septic shock, congestive heart failure, endotoxic shock, subarachnoid hemorrhage, arrhythmias, asthma, preeclampsia, atherosclerotic disorders including Raynaud's disease and restenosis, angina, cancer, pulmonary hypertension, ischemic disease, gastric mucosal damage, hemorrhagic shock, ischemic bowel disease, stroke, benign prosthatic hyperplasia (BPH), and diabetes.

Claims10

Dependent claims

A compound of formula ##STR461## or a tautomeric open chain keto-acid form thereof or a pharmaceutically acceptable salt thereof wherein

R.sub.1 is cycloalkyl substituted or unsubstituted of from 3 to 12 carbon atoms,
phenyl substituted with from 1 to 5 substituents, naphthyl unsubstituted or substituted with from 1 to 5 substituents, or
heteroaryl unsubstituted or substituted with from 1 to 5 substituents;
R.sub.2 is alkyl substituted or unsubstituted straight,
or branched of from 1 to 12 carbon atoms,
cycloalkyl substituted or unsubstituted of from 3 to 12 carbon atoms,
aryl which is unsubstituted or substituted with from 1 to 5 substituents,
heteroaryl which is unsubstituted or substituted with from 1 to 3 substituents;
R.sub.3 is alkyl substituted or unsubstituted straight, or
branched, of from 1 to 12 carbon atoms,
cycloalkyl substituted or unsubstituted of from 3 to 12 carbon atoms,
aryl which is unsubstituted or substituted with from 1 to 5 substituents,
heteroaryl which is unsubstituted or substituted with from 1 to 3 substituents;
R.sub.4 is hydroxy or OR.sub.5,
SR.sub.5, wherein R.sub.5 is alkyl or substituted alkyl of from 1 to 7 carbon atoms, or
(CH.sub.2).sub.n OR.sub.5 wherein n is an integer of from 1 to 3;
X is O or S;
with the proviso that when R.sub.1 is monosubstituted phenyl and the substituent is p-methoxy, R.sub.3 is not unsubstituted phenyl, monosubstituted phenyl, or mesityl and with the further proviso when R.sub.2 is alkyl substituted, the substituent is not oxygen at the .alpha.-position to the furanone ring;
and with the proviso that any of R.sub.1 through R.sub.4 are heterocyclic containing.

16 more elements

A compound selected from the group:

(.+-.)-3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-4(phenylmethyl)-5-(2-pro penyloxy)-2 (5H)-furanone,
acetaldehyde, 4-(1,3-benzodioxol-5-yl)-2-(4-chlorophenyl)-2,5-dihydro-5-oxo-3-(phenylm ethyl)-2-furanyl!oxo!-, (.+-.)-,
2(5H)-furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-5-(2,3-dihydroxypropoxy)-4-(ph enylmethyl)-, (.+-.)-,
acetic acid, 4-(1,3-benzodioxol-5-yl)-2-(4-chlorophenyl)-2,5-dihydro-3-(phenylmethyl) -5-oxo-2-furanyl!oxy!-, (.+-.)-,
2(5H)-furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-5-(3-hydroxyphenyl)methoxy!-4 -(phenylmethyl)-, (.+-.)-,
2(5H)-furanone, 3-(1,3-benzodioxol-5-yl)-5-hydroxy-5-(4-methylphenyl)-4-(phenylmethyl)-,
2(5H)-furanone, 3-(1,3-benzodioxol-5-yl)-5-hydroxy-5-phenyl-4-(phenylmethyl)-,
2(5H)-furanone, 3-(1,3-benzodioxol-5-yl)-5-hydroxy-5-phenyl-4-(2-thienylmethyl)-,
2(5H)-furanone, 3-(1,3-benzodioxol-5-yl)-5-hydroxy-5-phenyl-4-(3-thienylmethyl)-,
2(5H)-furanone, 5-(4-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-hydroxy-4-(pheny lmethyl)-,
2(5H)-furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-5-hydroxy-4-(2-thienylmethyl)-
2(5H)-furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-5-hydroxy-4-(1-naphthalenylmet hyl)-, (.+-.)-,
2(5H)-furanone, 4-(1,3-benzodioxol-5-ylmethyl)-5-(4-chlorophenyl)-5-hydroxy-3-4-(1-methyl ethyl)- phenyl!-, (.+-.)-,
2(5H)-furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-5-hydroxy-4-(2-naphthalenylmet hyl)-, (.+-.)-,
2(5H)-furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-5-hydroxy-4-4-(1-methylethyl )- phenyl!methyl!-, (.+-.)-,
2(5H)-furanone, 3-(1,3-benzodioxol-5-yl)-4-(1,3-benzodioxol-5-ylmethyl)-5-(4-chlorophenyl) -5-hydroxy-, (.+-.)-,
2(5H)-Furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-5-hydroxy-4-(3-thienylmethyl)-
2(5H)-Furanone, 4-(1,3-benzodioxol-5-ylmethyl)-5-(4-chlorophenyl)-3-4-(dimethyl-amino)phe nyl!-5-hydroxy-, (.+-.)-,
2(5H)-Furanone, 4-(1,3-benzodioxol-5-ylmethyl)-5-(4-chlorophenyl)-3-(3,4-dimethoxy-phenyl) -5-hydroxy, (.+-.)-,
2(5H)-Furanone, 4-(1,3-benzodioxol-5-ylmethyl)-5-(4-chlorophenyl)-3-(3,4-dichloro-phenyl)- 5-hydroxy-, (.+-.)-,
2(5H)-Furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-4-(phenylmethyl)-5-propoxy-, (.+-.)-,
2(5H)-Furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-4-(3-chlorophenyl)methyl!-5-h ydroxy,
3-Benzo1,3!dioxol-5-yl-4-(4-chlorobenzyl)-5-hydroxy-5-(4-methoxyphenyl)-5H -furan-2-one,
3Benzo1,3!dioxol-5-yl-4-(4-bromobenzyl)-5-hydroxy-5-(4-methoxy-phenyl)-5H- furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(4-benzyloxy-benzyl)-5-hydroxy-5-(4-methoxyphenyl )-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxyphenyl)-4-(4-trifluoromethylb enzyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-ethyl-5-hydroxy-5-(4-methoxyphenyl)-5H-furan-2-on e,
3-Benzo1,3!dioxol-5-yl-4-benzyl-5-(2,6-difluorophenyl)-5-hydroxy-5H-furan- 2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxyphenyl)-4-pyridin-3-ylmethyl- 5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4-isoquinolin-4-ylmethyl-5-(4-methoxyphen yl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-biphenyl-4-ylmethyl-5-hydroxy-5-(4-methoxyphenyl) -5H-furan-2-one,
2(5H)-Furanone, 3-(1,3-benzodioxol-5-yl)-5-hydroxy-4-(4-isoquinolinyl)-5-(4-methoxy-phenyl )-, (.+-.)-, monohydrochloride,
2(5H)-Furanone, 3-(1,3-benzodioxol-5-yl)-5-hydroxy-5-(4-methoxyphenyl)-4-(3-pyridinyl-meth yl)-, (.+-.)-, monohydrochloride,
2-Butenoic acid, 2-(1,3-benzodioxol-5-yl)-3-(4-methoxy-4-methylphenyl)methyl!-4-(4-methoxy phenyl)-4-oxo-, (Z)-, ion(1-) compd. with 2-hydroxy-N,N,N-trimethylethanaminium (1:1),
2-Butenoic acid, 2-(1,3-benzodioxol-5-yl)-4-(4-methoxyphenyl)-4-oxo-3-4-trifluoromethyl)p henyl!methyl!-, (Z)-, ion(1-) compd. with 2-hydroxy-N,N,N-trimethylethanaminium (1:1),
4'-Benzyl-5'-hydroxy-5'-(4-methoxyphenyl)-5'H-2,3'!bifuranyl-2-one,
4-Benzyl-5-hydroxy-5(4-methoxyphenyl)-3-thiophen-2-yl-5H-furan-2-one,
4-Benzyl-5-hydroxy-5-(4-methoxyphenyl)-5H-3,3'!bifuranyl-2-one,
3Benzo1,3!dioxol-5-yl-4-benzyl-5-(3,4-dimethoxyphenyl)-5-hydroxy-5H-furan- 2-one,
3Benzo1,3!dioxol-5-yl-4-benzyl-5-(3,4-dichlorophenyl)-5-hydroxy-5H-furan-2 -one,
4-(4-Benzo1,3!dioxol-5-yl-3-benzyl-2-hydroxy-5-oxo-2,5-dihydrofuran-2-yl) benzoic acid methyl ester,
4-4Benzo1,3!dioxol-5-yl-3-benzyl-2-hydroxy-5-oxo -2,5-dihydrofuran-2-yl) benzoic acid,
3-Benzo1,3!dioxol-5-yl-4-benzyl-5-hydroxy-5-(4-isopropoxyphenyl)-5H-furan- 2-one,
3Benzo1,3!dioxol-5-yl-4-benzyl-5-(4-benzyloxyphenyl)-5-hydroxy-5H-furan-2- one,
3Benzo1,3!dioxol-5-yl-4-benzyl-5-(3,4-dimethylphenyl)-5-hydroxy-5H-furan-2 -one,
3Benzo1,3!dioxol-5-yl-4-benzyl-5-hydroxy-5-o-tolyl-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-benzyl-5-hydroxy-5-(3-methoxyphenyl)-5H-furan-2-o ne,
3-Benzo1,3!dioxol-5-yl-4-benzyl-5-methoxy-5-(4-methoxyphenyl)-5H-furan-2-o ne,
3-Benzo1,3!dioxol-5-yl-4-benzyl-5-hydroxy-5-m-tolyl-5H-furan-2-one,
3Benzo1,3!dioxol-5-yl-4-benzyl-5-(3-chlorophenyl)-5-hydroxy-5H-furan-2-one
3,5-Bis-benzo1,3!dioxol-5-yl-4-benzyl-5-hydroxy-5H-furan-2-one,
3Benzo1,3!dioxol-5-yl-4-benzyl-5-hydroxy-5-(2-methoxyphenyl)-5H-furan-2-on e,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxyphenyl)-4-naphthalen -1-ylmethyl-5H-furan-2-one,
3Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxyphenyl)-4-(2-phenoxybenzyl-5H- furan-2-one,
3Benzo1,3!dioxol-5-yl-4-benzyl-5-(4-ethylphenyl)-5-hydroxy-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-benzyl-5-hydroxy-5-(4-methylsulfanylphenyl)-5H-fu ran-2-one,
4-4-benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxyphenyl)-5-oxo-2,5-dihydrof uran-3-ylmethyl!benzoic acid,
1,3-Benzodioxol-5-acetic acid, .alpha.-2-(4-carboxyphenyl)methyl!-2-(4-methoxybenzoyl)ethylidene!-, disodium salt,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxyphenyl)-4-(3,4,5-trimethoxy-b enzyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(2-chlorobenzyl-5-hydroxy-5-(4-methoxyphenyl)-5H- furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxyphenyl)-4-(2-methylbenzyl)-5H -furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4-(2-methoxybenzyl)-5-(4-methoxyphenyl)-5 H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4,5-bis-(4-methoxyphenyl)-5H-furan-2-one,
3-4-Benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxy-phenyl)-5-oxo-2,5-dihydro -furan-3-ylmethyl!-benzoic acid,
{4-4Benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxy-phenyl)-5-oxo-2,5-dihydro -furan-3-ylmethyl!-phenyl}-acetic acid,
{3-4Benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxy-phenyl)-5-oxo-2,5-dihydro -furan-3-ylmethyl!-phenyl}-acetic acid,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4-(4-methoxy-3,5-dimethyl-benzyl)-5-(4-me thoxy-phenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(3,5-dimethyl-4-isoproxy-benzyl)-5-hydroxy-5-(4-m ethoxy-phenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(6,6-dimethylbicyclo3.1.1!hept-2-en-2-ylmethyl)- 5-hydroxy-5-(4-methoxy-phenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxy-phenyl)-4-(2-phenoxy-benzyl) -5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(2-cyclohexylethyl)-5-hydroxy-5-(4-methoxy-phenyl )-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(2-allyloxy-4-methoxyphenyl)-4-benzyl-5 H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(2-cyclohexyl-2-phenyl-ethyl)-5-hydroxy-5-(4-meth oxy-phenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-cycloheptylmethyl-5-hydroxy-5-(4-methoxy-phenyl)- 5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxy-phenyl)-4-pentyl-5H-furan-2- one,
2-(4-Benzo1,3!dioxol-5-yl-3-benzyl-2-hydroxy-5-oxo-2,5-dihydro-furan-2-yl )-5-methoxy-phenoxy!-acetic acid,
{2-4-Benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxy-phenyl)-5-oxo-2,5-dihydr o-furan-3-ylmethyl!-5-methoxy-phenoxy}-acetic acid,
2-Butenoic acid, 2-(1,3-benzodioxol-5-yl)-4-4-(1H-imidazol-1-yl)phenyl!4-oxo-3-(phenyl-met hyl)-,
2-Benzo1,3!dioxol-5-yl-4-(4-methoxy-phenyl)-3-4-(2-morpholin-4-yl-ethylca rbamoyl)-benzyl!-4-oxo-but-2-enoic acid,
Benzamide, 4-4-(1,3-benzodioxol-5-yl)-2,5-dihydro-2-hydroxy-2-(4-methoxyphenyl)-5-o xo-3-furanyl!methyl!-N-2-(4-morpholinyl)ethyl!-, monohydrochloride, (.+-.)-,
{4-4Benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxy-phenyl)-5-oxo-2,5-dihydro -furan-3-ylmethyl!-2,6-dimethoxy-phenoxy}-acetic acid,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxy-3-methyl-phenyl)-4-(3-methox y-4-octyloxy-benzyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(4-cyclohexyloxy-3-methyl-benzyl)-5-hydroxy-5-(4- methoxy-phenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxy-phenyl)-4-(1,2,3,4-tetrahydr o-naphthalen-1-ylmethyl)-5H-furan-2-one,
3-4Benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxy-phenyl)-5-oxo-2,5-dihydro- furan-3-ylmethyl!-cyclohexanecarboxylic acid,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4-(4-isopropyl-benzyl)-5-(4-methoxy-pheny l)-5H-furan-2-one,
2(5H)-Furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-4-(4-chlorophenyl)methyl!-5-h ydroxy-,
2(5H)-Furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-5-hydroxy-4-(4-methoxyphenyl) methyl!-,
2(5H)-Furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-5-hydroxy-4-(4-methylphenyl)m ethyl!-,
2(5H)-Furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-5-hydroxy-4-(3-methylphenyl)m ethyl!-,
2(5H)-Furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-5-hydroxy-4-(3-methoxyphenyl) methyl!-,
2(5H)-Furanone, 3-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-5-hydroxy-4-(1-methyl-1H-indo l-3-yl)methyl!, (.+-.)-,
3-Benzo1,3!dioxol-5-yl-4-(3,5-dimethyl-4-octyloxy-benzyl)-5-hydroxy-5-(4-m ethoxy-phenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(3,5-dimethoxybenzyl)-5-methoxy-5-(4-methoxypheny l)-5H-furan-2-one.

91 more elements

A compound named:

2(5H)-Furanone, 3-(1,3-benzodioxol-5-yl)-5-hydroxy-5-(4-methoxyphenyl)-4-(phenylmethyl)-,
3-Benzo1,3!dioxol-5-yl-4-(3-chlorobenzyl)-5-hydroxy-5-(4-methoxyphenyl)-5H -furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxyphenyl)-4-(4-methylbenzyl)-5H -furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4-(4-methoxybenzyl)-5-(4-methoxyphenyl)-5 H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(4-tert-butylbenzyl)-5-hydroxy-5-(4-methoxyphenyl )-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxyphenyl)-4-(3-trifluoromethylb enzyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4-(isopropoxybenzyl)-5-(4-methoxyphenyl)- 5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(4-dimethylaminobenzyl)-5-hydroxy-5-(4-methoxylph enyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-benzo1,3!dioxol-5-ylmethyl-5-hydroxy-5-(4-methox yphenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4-(4-methoxy-3-methylbenzyl)-5-(4-methoxy phenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxyphenyl)-4-(3-methylbenzyl)-5H -furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(3-chloro-4-methoxybenzyl)-5-hydroxy-5-(4-methoxy phenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(4-butoxybenzyl)-5-hydroxy-5-(4-methoxyphenyl)-5H -furan-2-one,
3-(3,5-Dimethoxyphenyl)-5-hydroxy-5-(4-methoxyphenyl)-4-pyridin-3-ylmethyl- 5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxyphenyl)-4-(3-propoxybenzyl)-5 H-furan-2-one,
4-(3-Allyloxy-4-methoxy-enzyl)-3-benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-metho xyphenyl)-5H-furan-2-one,
2(5H )-Furanone, 3-(3,5-dimethoxyphenyl)-5-hydroxy-5-(4-methoxyphenyl)-4-(3-pyridinyl-methy l)-, (.+-.)-, monohydrochloride,
2-Butenoic acid, 2-(1,3-benzodioxol-5-yl)-4-(4-methoxyphenyl)-4-oxo-3-(phenylmethyl)-, (Z)-, ion(1-) compound with 2-hydroxy-N,N,N-triethanaminium (1:1),
3-Benzo1,3!dioxol-5-yl-4-cyclohexylmethyl-5-hydroxy-5-(4-methoxyphenyl)-5H -furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4-(4-methanesulfonylbenzyl)-5-(4-methoxyp henyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-benzyl-5-(2,4-dimethoxyphenyl)-5-hydroxy-5H-furan -2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4-(4-methoxy-2,5-dimethylbenzyl)-5-(4-met hoxy-phenyl)-5H-furan-2-one,
2-Butenoic acid, 2-(1,3-benzodioxol-5-yl)-4-(4-methoxyphenyl)-4-oxo-3-(3-propoxyphenyl)-me thyl!-, (Z)-, ion(1-) compound with 2-hydroxy-N,N,N-trimethylethanaminium (1:1),
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4-(4-methoxy-2,3-dimethylbenzyl)-5-(4-met hoxy-phenyl)-5H-furan-2-one,
4-(3-Allyloxy-4-methoxybenzyl)-3-benzo1,3!dioxol-5-yl-5-(2,4-dimethoxyphen yl)-5-hydroxy-5H-furan-2-one,
Benzoic acid, 3-4-(1,3-benzodioxol-5-yl)-2,5-dihydro-2-hydroxy-2-(4-methoxyphenyl)-5-o xo-3-furanyl!methyl!-, methyl ester,
2(5H)-Furanone, 3-(1,3-benzodioxol-5-yl)-5-hydroxy-5-(4-methoxy-3-methylphenyl)-4-(phenylm ethyl)-, (.+-.)-,
{4-4-Benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxy-phenyl)-5-oxo-2,5-dihydr o-furan-3-ylmethyl!-phenyl}-acetic acid methyl ester,
{3-4-Benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxy-phenyl)-5-oxo-2,5-dihydr o-furan-3-ylmethyl!-phenyl}-acetic acid methyl ester,
4-Benzyl-5-hydroxy-3-(7-methoxy-benzo1,3!-dioxol-5-yl)-5-(4-methoxy-phenyl )-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(3,5-dimethoxybenzyl)-5-hydroxy-5-(4-methoxy-phen yl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(3,4-dimethoxy-benzyl)-5-hydroxy-5-(4-methoxy-phe nyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxyphenyl)-4-(2,3,4-trimethoxy-b enzyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxyphenyl)-4-(2,4,5-trimethoxy-b enzyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(2,5-dimethoxybenzyl)-5-hydroxy-5-(4-methoxy-phen yl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(2,3-dimethoxybenzyl)-5-hydroxy-5-(4-methoxy-phen yl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(4-benzyloxy-3-methoxybenzyl)-5-hydroxy-5-(4-meth oxy-phenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-cyclopentylmethyl-5-hydroxy-5-(4-methoxy-phenyl)- 5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-cyclohex-3-enyl-methyl-5-hydroxy-5-(4-methoxy-phe nyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(2-cyclopentyl-2-phenyl-ethyl)-5-hydroxy-5-(4-met hoxy-phenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-2-(benzo1,3!-dioxol-5-yloxy)-benzyl!-5-hydroxy- 5-(4-methoxyphenyl)-5H-furan-2-one,
4-(2-Allyloxy-4-methoxy-benzyl)-3-benzo1,3!-dioxol-5-yl-5-hydroxy-5-(4-met hoxy-phenyl)-5H-furan-2-one,
Sodium 2-benzo1,3!dioxol-5-yl-3-benzyl-4-(4-methoxyphenyl)-4-oxobut-2-enoate,
1,3-Benzodioxol-5-acetic acid, .alpha.-2-(4-methoxyphenyl)-1-4-(1-methylethoxy)phenyl!methyl!-2-oxoeth ylene!-, (Z)-, choline salt,
Sodium 2-benzo1,3!dioxol-5-yl-3-benzyl-4-(4-methoxyphenyl)-4-oxobut-2-enoate,
Sodium 2-benzo1,3!dioxol-5-yl-3-(4-isopropoxybenzyl)-4-(4-methoxy-phenyl)-4-oxob ut-2-enoate,
5-Hydroxy-3-(7-methoxy-benzo1,3!dioxol-5-yl)-5-(4-methoxy-phenyl)-4-(3,4,5 -trimethoxybenzyl)-5H-furan-2-one,
4-Benzyl-5-hydroxy-3-(7-methoxy-benzo1,3!-dioxol-5-yl)-5-(4-methoxy-3-meth yl-phenyl)-5H-furan-2-one,
5-Hydroxy-3-(7-methoxy-benzo1,3!dioxol-5-yl)-5-(4-methoxy-3-methyl-phenyl) -4-(3,4,5-trimethoxy-benzyl)-5H-furan-2-one,
{4-4-Benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxy-phenyl)-5-oxo-2,5-dihydr o-furan-3-ylmethyl!-2,6-dimethoxy-phenoxy}-acetic acid ethyl ester,
{5-4-Benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxy-phenyl)-5-oxo-2,5-dihydr o-furan-3-ylmethyl!-2,3-dimethoxy-phenoxy}-acetic acid ethyl ester,
{4-4-Benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxy-phenyl)-5-oxo-2,5-dihydr o-furan-3-ylmethyl!-2,3-dimethoxy-phenoxy}-acetic acid,
Sodium 2-benzo1,3!dioxol-5-yl-3-(4-methoxybenzoyl)-4-(4-methoxy-2,5-dimethylphen yl)-but-2-enoate,
Sodium 3-benzyl-2-(7-methoxybenzo1,3!dioxol-5-yl)-4-(4-methoxyphenyl)-4-oxobut-2 -enoate,
Sodium 2-(7-methoxybenzo-1,3!dioxol-5-yl)-3-(4-methoxy-3-methylbenzoyl-4-(3,4,5- trimethoxy-phenyl)-but-2-enoate,
Sodium 2-(7-methoxybenzo-1,3!dioxol-5-yl)-4-(4-methoxyphenyl)-4-oxo-3-(3,4,5-tri methoxy-benzyl)-but-2-enoate,
Sodium 2-Benzo1,3!dioxol-5-yl-3-cyclohexylmethyl-4-(4-methoxy-phenyl)-4-oxo-but- 2-enoate,
Sodium 2-Benzo1,3!dioxol-5-yl-3-(4-methoxybenzyl)-4-(4-methoxy-phenyl)-4-oxo-but -2-enoate,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-5-(4-methoxy-3-methyl-phenyl)-4-(3,4,5-tr imethoxy-benzyl)-5H-furan-2-one,
N -{4-4-Benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxy-3-methyl-phenyl)-5-oxo -2,5-dihydro-furan-3-ylmethyl!-phenyl}-acetamide,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4-(4-isopropoxy-3-methoxy-benzyl)-5-(4-me thoxy-3-methyl-phenyl)-5H-furan-2-one,
3Benzo1,3!dioxol-5-yl-5-hydroxy-4-(4-isopropoxy-3-methyl-benzyl)-5-(4-meth oxy-3-methyl-phenyl)-5H-furan-2-one,
3-4-Benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxy-phenyl)-5-oxo-2,5-dihydro -furan-3-ylmethyl!-cyclohexanecarboxylic acid methyl ester,
3-Benzo1,3!dioxol-5-yl-4-cyclopropylmethyl-5-hydroxy-5-(4-methoxy-phenyl)- 5H-furan-2-one,
1,3-Benzodioxol-5-acetic acid, .alpha.-1-3-(methoxycarbonyl)phenyl!methyl!-2-(4-methoxy-phenyl)-2-oxoe thylene!-, monopotassium salt,
1,3-Benzodioxole-5-acetic acid, .alpha.-1-(4-methoxybenzoyl)-2-(2-methoxyphenyl)ethylidene!-, monosodium salt, (Z)-,
4-Cyclohexylmethyl-5-hydroxy-3-(7-methoxybenzo1,3!dioxol-5-yl)-5-(4-methox y-3-methyl-phenyl)-5H-furan-2-one,
4-Cyclohexylmethyl-5-hydroxy-3-(7-methoxybenzo1,3!dioxol-5-yl)-5-(4-methox y-phenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4-(4-iodobenzyl)-5-(4-methoxy-phenyl)-5H- furan-2-one,
3Benzo1,3!dioxol-5-yl-4-(3,5-dimethoxy-4-pentyloxy-benzyl)-5-hydroxy-5-(4- methoxy-phenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(4-butoxy-3,5-dimethoxybenzyl)-5-hydroxy-5-(4-met hoxy-phenyl)-5H-furan-2-one,
3Benzo1,3!dioxol-5-yl-4-(3-benzyloxy-4,5-dimethoxy-benzyl)-5-hydroxy-5-(4- methoxy-phenyl)-5H-furan-2-one,
4-(3-Alkyloxy-4,5-dimethoxy-benzyl)-3-benzo-1,3!dioxol-5-yl-5-hydroxy-5-(4 -methoxy-phenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-(2,4-dimethoxy-benzyl)-5-hydroxy-5-(4-methoxy-phe nyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4-(3-isopropoxy-4,5-dimethoxy-benzyl)-5-( 4-methoxy-phenyl)-5H-furan-2-one,
4-Cyclopentylmethyl-5-hydroxy-3-(7-methoxybenzo1,3!dioxol-5-yl)-5-(4-metho xy-3-methyl-phenyl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-4-2-cyclopentyl-2-(4-methoxyphenyl)-ethyl!-5-hydro xy-5-(4-methoxy-phenyl)-5H-furan-2-one,
5-Benzo1,3!dioxol-5-yl-4-cyclopentylmethyl-5-hydroxy-3-(7-methoxy-benzo1, 3!dioxyl-5-yl)-5H-furan-2-one,
5-Benzo1,3!dioxol-5-yl-4-cyclohexylmethyl-5-hydroxy-3-(7-methoxy-benzo1,3 !dioxol-5-yl)-5H-furan-2-one,
5-Benzo1,3!dioxol-5-yl-5-hydroxy-3-(7-methoxybenzo1,3!dioxol-5-yl)-4-4-m ethoxy-2-(2-methoxyethoxy)-benzyl!-5H-furan-2-one,
4-Cyclopentylmethyl-5-hydroxy-3-(7-methoxybenzo1,3!dioxol-5-yl)-5-(4-metho xy-phenyl)-5H-furan-2-one,
4-Cyclohexylmethyl-5-hydroxy-5-(7-methoxybenzo1,3!dioxol-5-yl)-3-(4-methox y-phenyl)-5H-furan-2-one,
4-Cyclohexylmethyl-5-(2,3-dihydro-benzo1,4!dioxin-6-yl)-5-hydroxy-3-(7-met hoxy-benzo1,3!-dioxol-5-yl)-5H-furan-2-one,
3-Benzo1,3!dioxol-5-yl-5-hydroxy-4-(3-methoxymethyl-benzyl)-5-(4-methoxy-p henyl)-5H-furan-2-one,
4-Cyclopentylmethyl-5-(2,3-dihydro-benzo1,4!dioxin-6-yl)-5-hydroxy-3-(7-me thoxy-benzo1,3!-dioxol-5-yl)-5H-furan-2-one, and
4-Cyclopentylmethyl-5-hydroxy-3,5-bis-(7-methoxybenzo1,3!dioxol-5-yl)-5H-f uran-2-one,
3-Benzo1,3!dioxol-5-yl-4-(3,4-dichlorobenzyl)-5-hydroxy-5-(4-methoxyphenyl )-5H-furan-2-one,
N-{4-4-Benzo1,3!dioxol-5-yl-2-hydroxy-2-(4-methoxyphenyl)-5-oxo-2,5-dihyd ro-furan-3-ylmethyl!-phenyl}-acetamide,
Sodium 2-Benzo1,3!dioxol-5-yl-4-(4-methoxyphenyl)-4-oxo-3-(3,4,5-trimethoxy-benz yl)-but-2-enoate,
Potassium 3-(4-Acetylamino-benzyl)-2-benzo1,3!-dioxol-5-yl-4-(4-methoxy-phenyl)-4-o xo-but-2-enoate,
Sodium 3-Benzyl-2-(7-methoxy-benzo1,3!dioxol-5-yl)-4-(4-methoxy-3-methyl-phenyl) -4-oxo-but-2-enoate,
Sodium 2-Benzo1,3!dioxol-5-yl-4-(4-methoxy-3-methyl-phenyl)-4-oxo-3-(3,4,5-trime thoxy-benzyl)-but-2-enoate.

89 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/384,083Filed 6 Feb 1995 · continuation in part
Priority: 19 Aug 1993
Granted: 25 Nov 1997
Term ends: Not estimatedThe source records don’t support an estimate.

Classification28 codes

C07D 405/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
A61P 3/08
Drugs for disorders of the metabolism: for glucose homeostasis
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/08
Drugs for disorders of the cardiovascular system: vasodilators for multiple indications