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US 5,491,172 AGranted
N-acyl sulfamic acid esters (or thioesters), N-acyl sulfonamides, and N-sulfonyl carbamic acid esters (or thioesters) as hypercholesterolemic agents
AssigneeWarner-Lambert Company
InventorsHelen T. Lee, Joseph A. Picard, Drago R. Sliskovic, Wendell Wierenga
Life of this patent
Estimating the term…
Abstract
The present invention is directed to compounds useful for the regulation of cholesterol of Formula I, methods for using them and pharmaceutical compositions thereof, ##STR1## wherein X and Y are oxygen, sulfur, or (CR'R").sub.n wherein n is 1 to 4; R is hydrogen, alkyl, or benzyl; R.sub.1 and R.sub.2 are phenyl, substituted phenyl, naphthyl, substituted naphthyl, an aralkyl group, an alkyl chain, adamantyl, or a cycloalkyl group.
Claims17
A compound of the formula
- or a pharmaceutically acceptable salt thereof wherein:
- X is oxygen;
- Y is (CR'R").sub.n wherein n is an integer of from 1 to 4 and R' and R" are each independently hydrogen, alkyl, alkoxy, halogen, hydroxy, acyloxy, cycloalkyl, phenyl optionally substituted or R' and R" together form a spirocycloalkyl or a carbonyl;
- R is hydrogen, a straight or branched alkyl of from 1 to 8 carbon atoms or benzyl;
- R.sub.1 and R.sub.2 are each independently selected from
- (a) phenyl or phenoxy each of which is unsubstituted or is substituted with 1 to 5 substituents selected from
- phenyl,
- an alkyl group having from 1 to 6 carbon atoms and which is straight or branched,
- an alkoxy group having from 1 to 6 carbon atoms and which is straight or branched;
- phenoxy,
- hydroxy,
- fluorine,
- chlorine,
- bromine,
- nitro,
- trifluoromethyl,
- --COOH,
- --COOalkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched,
- --(CH.sub.2).sub.p NR.sub.3 R.sub.4 wherein p is zero or one, and each of R.sub.3 and R.sub.4 is selected from hydrogen or a straight or branched alkyl group having 1 to 4 carbon atoms;
- (b) 1- or 2-naphthyl unsubstituted or substituted with from 1 to 3 substituents selected from
- phenyl,
- an alkyl group having from 1 to 6 carbon atoms and which is straight or branched,
- an alkoxy group having from 1 to 6 carbon atoms and which is straight or branched;
- hydroxy,
- phenoxy,
- fluorine,
- chlorine,
- bromine,
- nitro,
- trifluoromethyl,
- --COOH,
- --COOalkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched,
- --(CH.sub.2).sub.p NR.sub.3 R.sub.4 wherein p, R.sub.3 and R.sub.4 have the meanings defined above;
- (c) arylalkyl;
- (d) a straight or branched alkyl chain having from 1 to 20 carbon atoms and which is saturated or contains from 1 to 3 double bonds;
- or
- (e) adamantyl or a cycloalkyl group wherein the cycloalkyl moiety has from 3 to 6 carbon atoms.
34 more elements
A pharmaceutical composition for regulating plasma cholesterol concentrations comprising an effective amount of a compound of formula ##STR7## or a pharmaceutically acceptable salt thereof wherein:
- X is oxygen;
- Y is (CR'R").sub.n wherein n is an integer of from 1 to 4 and R' and R" are each independently hydrogen, alkyl, alkoxy, halogen, hydroxy, acyloxy, cycloalkyl, phenyl optionally substituted or R' and R" together form a spirocycloalkyl or a carbonyl;
- R is hydrogen, a straight or branched alkyl of from 1 to 8 carbon atoms or benzyl;
- R.sub.1 and R.sub.2 are each independently selected from
- (a) phenyl or phenoxy each of which is unsubstituted or is substituted with 1 to 5 substituents selected from
- phenyl,
- an alkyl group having from 1 to 6 carbon atoms and which is straight or branched,
- an alkoxy group having from 1 to 6 carbon atoms and which is straight or branched;
- phenoxy,
- hydroxy,
- fluorine,
- chlorine,
- bromine
- nitro,
- trifluoromethyl,
- --COOH,
- --COOalkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched,
- --(CH.sub.2).sub.p NR.sub.3 R.sub.4 wherein p is zero or one, and each of R.sub.3 and R.sub.4 is selected from hydrogen or a straight or branched alkyl group having 1 to 4 carbon atoms;
- (b) 1- or 2-naphthyl unsubstituted or substituted with from 1 to 3 substituents selected from
- phenyl,
- an alkyl group having from 1 to 6 carbon atoms and which is straight or branched,
- an alkoxy group having from 1 to 6 carbon atoms and which is straight or branched;
- hydroxy,
- phenoxy,
- fluorine,
- chlorine,
- bromine,
- nitro,
- trifluoromethyl,
- --COOH,
- --COOalkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched,
- --(CH.sub.2).sub.p NR.sub.3 R.sub.4 wherein p, R.sub.3 and R.sub.4 have the meanings defined above;
- (c) arylalkyl;
- (d) a straight or branched alkyl chain having from 1 to 20 carbon atoms and which is saturated or contains from 1 to 3 double bonds;
- or
- (e) adamantyl or a cycloalkyl group wherein the cycloalkyl moiety has from 3 to 6 carbon atoms and a pharmaceutically acceptable carrier.
33 more elements
A method of treating hypercholesterolemia comprising adminsitering to a patient a therapeutically effective amount of a compound of formula ##STR8## or a pharmaceutically acceptable salt thereof wherein:
- X is oxygen;
- Y is (CR'R").sub.n wherein n is an integer of from 1 to 4 and R' and R" are each independently hydrogen, alkyl, alkoxy, halogen, hydroxy, acyloxy, cycloalkyl, phenyl optionally substituted or R' and R" together form a spirocycloalkyl or a carbonyl;
- R is hydrogen, a straight or branched alkyl of from 1 to 8 carbon atoms or benzyl;
- R.sub.1 and R.sub.2 are each independently selected from
- (a) phenyl or phenoxy each of which is unsubstituted or is substituted with 1 to 5 substituents selected from
- phenyl,
- an alkyl group having from 1 to 6 carbon atoms and which is straight or branched,
- an alkoxy group having 1 to 6 carbon atoms and which is straight or branched;
- phenoxy,
- hydroxy,
- fluorine,
- chlorine,
- bromine,
- nitro,
- trifluoromethyl,
- --COOH,
- --COOalkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched,
- --(CH.sub.2).sub.p NR.sub.3 R.sub.4 wherein p is zero or one, and each of R.sub.3 and R.sub.4 is selected from hydrogen or a straight or branched alkyl group having 1 to 4 carbon atoms;
- (b) 1- or 2-naphthyl unsubstituted or substituted with from 1 to 3 substituents selected from
- phenyl,
- an alkyl group having from 1 to 6 carbon atoms and which is straight or branched,
- an alkoxy group having from 1 to 6 carbon atoms and which is straight or branched;
- hydroxy,
- phenoxy,
- fluorine,
- chlorine,
- bromine,
- nitro,
- trifluoromethyl,
- --COOH,
- --COOalkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched,
- --(CH.sub.2).sub.p NR.sub.3 R.sub.4 wherein p, R.sub.3 and R.sub.4 have the meanings defined above;
- (c) arylalkyl;
- (d) a straight or branched alkyl chain having from 1 to 20 carbon atoms and which is saturated or contains from 1 to 3 double bonds;
- or
- (e) adamantyl or a cyclcoalkyl group having wherein the cycloalkyl moiety has from 3 to 6 carbon atoms.
33 more elements
A method of treating atherosclerosis comprising adminsitering to a patient a therapeutically effective amount of a compound of formula ##STR9## or a pharmaceutically acceptable salt thereof wherein:
- X is oxygen;
- Y is (CR'R").sub.n wherein n is an integer of from 1 to 4 and R' and R" are each independently hydrogen, alkyl, alkoxy, halogen, hydroxy, acyloxy, cycloalkyl, phenyl optionally substituted or R' and R" together form a spirocycloalkyl or a carbonyl;
- R is hydrogen, a straight or branched alkyl of from 1 to 8 carbon atoms or benzyl;
- R.sub.1 and R.sub.2 are each independently selected from
- (a) phenyl or phenoxy each of which is unsubstituted or is substituted with 1 to 5 substituents selected from
- phenyl,
- an alkyl group having from 1 to 6 carbon atoms and which is straight or branched,
- an alkoxy group having from 1 to 6 carbon atoms and which is straight or branched;
- phenoxy,
- hydroxy,
- fluorine,
- chlorine,
- bromine,
- nitro,
- trifluoromethyl,
- --COOH,
- --COOalkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched,
- --(CH.sub.2).sub.p NR.sub.3 R.sub.4 wherein p is zero or one, and each of R.sub.3 and R.sub.4 is selected from hydrogen or a straight or branched alkyl group having 1 to 4 carbon atoms;
- (b) 1- or 2-naphthyl unsubstituted or substituted with from 1 to 3 substituents selected from
- phenyl,
- an alkyl group having from 1 to 6 carbon atoms and which is straight or branched,
- an alkoxy group having from 1 to 6 carbon atoms and which is straight or branched,
- hydroxy,
- phenoxy,
- fluorine,
- chlorine,
- bromine,
- nitro,
- trifluoromethyl,
- --COOH,
- --COOalkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched,
- --(CH.sub.2).sub.p NR.sub.3 R.sub.4 wherein p, R.sub.3 and R.sub.4 have the meanings defined above;
- (c) arylalkyl;
- (d) a straight or branched alkyl chain having from 1 to 20 carbon atoms and which is saturated or contains from 1 to 3 double bonds;
- or
- (e) adamantyl or a cycloalkyl group wherein the cycloalkyl moiety has from 3 to 6 carbon atoms.
33 more elements
A compound named sulfamic acid[[2,4,6-tris(1-methylethyl)phenyl]acetyl-2,6-bis(1-methylethyl)phenyl ester.
Dependencies are inferred from the claim text.