N-acyl sulfamic acid esters (or thioesters), N-acyl sulfonamides, and N-sulfonyl carbamic acid esters (or thioesters) as hypercholesterolemic agents

Claim 2

A compound of the formula or a pharmaceutically acceptable salt thereof wherein: X is oxygen; Y is (CR'R") 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 1 and R 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 2 ) p NR 3 R 4 wherein p is zero or one, and each of R 3 and R 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 2 ) p NR 3 R 4 wherein p, R 3 and R 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.

Claim 3

A compound of claim 1 wherein R 1 is phenyl.

Claim 4

A compound of claim 2 wherein R 1 is phenyl disubstituted in the 2,6-positions.

Claim 5

A compound of claim 1 wherein R 2 is phenyl.

Claim 6

A compound of claim 4 wherein R 2 is phenyl disubstituted in the 2,6-positions.

Claim 7

A compound of claim 1 wherein each of R 1 and R 2 is phenyl.

Claim 8

A compound of claim 6 wherein each phenyl is disubstituted in the 2,6-positions.

Claim 9

A compound of claim 1 wherein R 1 is phenyl disubstituted in the 2,6-positions and R 2 is phenyl trisubstituted in the 2,4,6-positions.

Claim 10

A compound of claim 1 wherein R 1 is 2,6-bis(1-methylethyl)phenyl and R 2 is 2,6-bis(1-methylethyl)phenyl or 2,4,6-tris(1-methylethyl)phenyl.

Claim 11

A compound of claim 1 wherein R 1 is phenyl or phenyl disubstituted in the 2,6-positions, wherein R 2 is phenyl or is phenyl disubstituted in the 2,6-positions, wherein each of R 1 and R 2 is phenyl, wherein each phenyl is disubstituted in the 2,6-position, wherein R 1 is phenyl disubstituted in the 2,6-positions and R 2 is phenyl trisubstituted in the 2,4,6-positions, wherein R 1 is 2,6-bis(1-methylethyl)phenyl and R 2 is 2,6-bis(1-methylethyl)phenyl or 2,4,6-tris(1-methylelthyl)phenyl, wherein one of R 1 and R 2 is the group ##STR6## wherein t is zero or 1 to 4; w is zero or 1 to 4 with the proviso that the sum of t and w is not greater than 5; R 5 and R 6 are each independently selected from hydrogen or alkyl having from 1 to 6 carbon atoms, or when R 5 is hydrogen, R 6 can be selected from the groups defined for R 7 ; and R 7 is phenyl or phenyl substituted with from 1 to 3 substituents selected from a straight or branched alkyl group having from 1 to 6 carbon atoms, straight or branched alkoxy group having from 1 to 6 carbon atoms, phenoxy, hydroxy, fluorine, chlorine, bromine, nitro, trifluoromethyl, --COOH, COOalkyl wherein alkyl has from 1 to 4 carbon atoms, or --(CH 2 ) p NR 3 R 4 wherein P, R 3 and R 4 have the meanings defined above.

Claim 12

A compound according to claim 1 wherein X is oxygen; Y is (CR'R") n wherein n is an integer of from 1 to 4 and R' and R" are each independently hydrogen, straight or branched alkyl of from 1 to 6 carbons, optionally substituted phenyl, halogen, hydroxy, alkoxy, acyloxy, cycloalkyl, or R' and R" taken together form a carbonyl or a spirocycloalkyl group of from 3 to 10 carbons; R is hydrogen; R 1 is phenyl optionally substituted, straight or branched alkyl of from 1 to 10 carbon atoms, cycloalkyl of from 3 to 10 carbon atoms; R 2 is phenyl optionally substituted, straight or branched alkyl of from 1 to 10 carbon atoms, cycloalkyl of from 3 to 8 carbon atoms, phenoxy optionally substituted.

Claim 13

A compound according to claim 1 wherein X is oxygen; Y is (CR'R") n wherein n is an integer of from 1 to 2; R is hydrogen; R 1 is optionally substituted phenyl; R 2 is optionally substituted phenyl or phenoxy, straight or branched alkyl of from 1 to 10 carbons, or cycloalkyl of from 3 to 10 carbons; R' and R" are each independently hydrogen, straight or branched alkyl of from 1 to 6 carbons, optionally substituted phenyl, halogen, hydroxy, alkoxy, acyloxy, cycloalkyl, or R' and R" taken together form a carbonyl or a spirocycloalkyl.

Claim 14

A compound of claim 1 selected from: Sulfamic acid (phenylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid[[2,6-bis(1-methylethyl)phenyl]acetyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [[2,4,6-tris(1-methylethyl)phenyl]acetyl-2,4,6-tris(1-methylethyl)phenyl ester, Sulfamic acid[[2,6-bis(1-methylethyl)phenyl]acetyl]-2,4,6-tris(1-methylethyl)phenyl ester, Sulfamic acid[adamantaneacetyl]-2,6-bis[1-methylethyl)phenyl ester, Sulfamic acid[[2,6-bis(1-methylethyl)phenyl]acetyl]-2,6-bis(1-methylethyl)phenyl ester-sodium salt, Sulfamic acid[[2,4,6-tris(1-methylethyl)phenyl]acetyl]-2,6-bis(1-methylethyl)phenyl ester-sodium salt, Sulfamic acid (decanoyl)-2,6-bis-(1-methylethyl)phenyl ester, Sulfamic acid (dodecanoyl)-2,6-bis-(1-methylethyl)phenyl ester,

Claim 15

6-Bis(1-methylethyl)-N-[[[2,4,6-tris(1-methylethyl)phenyl]methyl]sulfonyl]benzeneacetamide, 2,6-Bis(1-methylethyl)-N-[[[2,4,6-tris(1-methylethyl)phenyl]methyl]sulfonyl]benzeneacetamide-sodium salt. 2,6-Bis(1-methylethyl)phenyl[[[2,4,6-tris(1-methylethyl)phenyl]methyl]sulfonyl]carbamate, 2,6-Bis(1-methylethyl)phenyl[[[2,4,6-tris(1-methylethyl)phenyl]methyl]sulfonyl]carbamate-sodium salt, Sulfamic acid (1-oxo-3,3-diphenylpropyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2,6-dichlorophenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2,6-dichlorophenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid trans-[(2-phenylcyclopropyl)carbonyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2,5-dimethoxyphenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2,4,6-trimethoxyphenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2,4,6-trimethylphenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2-thiophenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [3-thiophenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2-methoxyphenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (oxophenylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2-trifluoromethylphenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (1-oxo-2-phenylpropyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (cyclopentylphenylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (cyclohexylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (diphenylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (triphenylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [(1l-phenylcyclopentyl)carbonyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (3-methyl-1-oxo-2-phenylpentyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (1-oxo-2-phenylbutyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (cyclohexylphenylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (1-oxo-2,2-diphenylpropyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [(9H-fluoren-9-yl)carbonyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (1-oxo-3-phenylpropyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [1-oxo-3-[2,4,6-tris(1-methylethyl)phenyl-2-propenyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [1-oxo-3-[2,4,6-tris(1-methylethyl)phenyl]propyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [(acetyloxy)[2,4,6-tris(1-methylethyl)phenyl]acetyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [hydroxy[2,4,6-tris(1-methylethyl)phenyl]acetyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [fluoro[2,4,6-tris(1-methylethyl)phenyl]acetyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (3-methyl-1-oxo-2-phenylpentyl)-2,6-bis(1-methylethyl)phenyl ester sodium salt, Sulfamic acid [[2,4,6-tris(1-methylethyl)phenoxy]acetyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [[2,6-bis(1-methylethyl)phenoxy]acetyl]-2,6-bis(1-methylethyl)phenyl ester, and Sulfamic acid [[2,4,6-tris(1-methylethyl)phenyl]acetyl]-2,6-bis(phenyl)phenyl ester.

Claim 16

6-Bis(1-methylethyl)-N-[[[2,4,6-tris(1-methylethyl)phenyl]methyl]sulfonyl]benzeneacetamide, 2,6-Bis(1-methylethyl)-N-[[[2,4,6-tris(1-methylethyl)phenyl]methyl]sulfonyl]benzeneacetamide-sodium salt. 2,6-Bis(1-methylethyl)phenyl[[[2,4,6-tris(1-methylethyl)phenyl]methyl]sulfonyl]carbamate, 2,6-Bis(1-methylethyl)phenyl[[[2,4,6-tris(1-methylethyl)phenyl]methyl]sulfonyl]carbamate-sodium salt, Sulfamic acid (1-oxo-3,3-diphenylpropyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2,6-dichlorophenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2,6-dichlorophenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid trans-[(2-phenylcyclopropyl)carbonyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2,5-dimethoxyphenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2,4,6-trimethoxyphenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2,4,6-trimethylphenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2-thiophenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [3-thiophenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2-methoxyphenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (oxophenylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [2-trifluoromethylphenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (1-oxo-2-phenylpropyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (cyclopentylphenylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (cyclohexylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (diphenylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (triphenylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [(1l-phenylcyclopentyl)carbonyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (3-methyl-1-oxo-2-phenylpentyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (1-oxo-2-phenylbutyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (cyclohexylphenylacetyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (1-oxo-2,2-diphenylpropyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [(9H-fluoren-9-yl)carbonyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (1-oxo-3-phenylpropyl)-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [1-oxo-3-[2,4,6-tris(1-methylethyl)phenyl-2-propenyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [1-oxo-3-[2,4,6-tris(1-methylethyl)phenyl]propyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [(acetyloxy)[2,4,6-tris(1-methylethyl)phenyl]acetyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [hydroxy[2,4,6-tris(1-methylethyl)phenyl]acetyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [fluoro[2,4,6-tris(1-methylethyl)phenyl]acetyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid (3-methyl-1-oxo-2-phenylpentyl)-2,6-bis(1-methylethyl)phenyl ester sodium salt, Sulfamic acid [[2,4,6-tris(1-methylethyl)phenoxy]acetyl]-2,6-bis(1-methylethyl)phenyl ester, Sulfamic acid [[2,6-bis(1-methylethyl)phenoxy]acetyl]-2,6-bis(1-methylethyl)phenyl ester, and Sulfamic acid [[2,4,6-tris(1-methylethyl)phenyl]acetyl]-2,6-bis(phenyl)phenyl ester.

Claim 17

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") 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 1 and R 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 2 ) p NR 3 R 4 wherein p is zero or one, and each of R 3 and R 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 2 ) p NR 3 R 4 wherein p, R 3 and R 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.

Claim 18

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") 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 1 and R 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 2 ) p NR 3 R 4 wherein p is zero or one, and each of R 3 and R 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 2 ) p NR 3 R 4 wherein p, R 3 and R 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.

Claim 23

A compound named sulfamic acid[[2,4,6-tris(1-methylethyl)phenyl]acetyl-2,6-bis(1-methylethyl)phenyl ester.

Claim 24

A compound named sulfamic acid[[2,4,6-tris(1-methylethyl)phenyl]acetyl-2,6-bis(1-methylethyl)phenyl ester.