4-substituted piperidinecarboxylic acid esters: inhibition of cholesterol absorption

Claim 2

A compound of the formula: ##STR12## in which R 1 is H, C 1 -C 20 alkyl, C 3 -C 20 alkenyl, C 3 -C 8 cycloalkyl, cycloalkylalkyl where the cycloalkyl moiety has from 3 to 8 carbon atoms and the alkyl moiety has from 1 to 6 carbon atoms, phenyl, phenyl substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano or trifluoromethyl; phenylalkyl where the alkyl moiety has from 1 to 20 carbons, or phenylalkyl where the phenyl group is substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano, trifluoromethyl or phenyl; R 2 is H or C 1 -C 6 alkyl; or R 1 and R 2 taken together with the interposed nitrogen forms a heterocyclic group of the formula: ##STR13## where n is one of the intergers 0, 1 or 2; X is --O--, --S--, or ##STR14## and R 7 is H, hydroxy, C 1 -C 6 alkyl, C 2 -C 6 alkanoyloxy, C 1 -C 6 hydroxyalkyl, carboxyl, C 1 -C 16 alkoxycarbonyl, phenyl or phenyl substituted with C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 perhaloalkyl, halo, nitro or cyano; R 8 is H or C 1 -C 6 alkyl or R 7 and R 8 taken together with the intervening carbon atom forms a polymethylene ring of 3 to 7 carbon atoms; R 9 is H, C 1 -C 6 alkyl or C 2 -C 12 gemdialkyl; and R 3 , R 4 , R 5 and R 6 are H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano, C 1 -C 6 perhaloalkyl, C 1 -C 16 alkoxycarbonyl, or carboxyl.

Claim 3

A compound of the formula: ##STR15## in which R 1 is C 1 -C 20 alkyl, C 3 -C 20 alkenyl, C 3 -C 8 cycloalkyl, cycloalkylalkyl in which the cycloalkyl moiety has from 3 to 8 carbon atoms and the alkyl moiety has from 1 to 6 carbon atoms, phenylalkyl where the alkyl moiety has from 1 to 20 carbon atoms, and substituted phenylalkyl where the phenyl group is substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano, trifluoromethyl, or phenyl; R 2 is H or C 1 -C 6 alkyl, or R 1 and R 2 taken together with the interposed nitrogen forms a heterocyclic group of the formula: ##STR16## where n is one of the integers 0, 1 or 2; X is --S-- or ##STR17## and R 7 is H, hydroxy, C 1 -C 6 alkyl, phenyl or phenyl substituted by C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halo, nitro, cyano or trifluoromethyl; R 8 is H or C 1 -C 6 alkyl; and R 3 , R 4 , R 5 and R 6 are H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano, C 1 -C 6 perhaloalkyl, C 1 -C 16 alkoxycarbonyl or carboxyl.

Claim 4

A compound of the formula: ##STR15## in which R 1 is C 1 -C 20 alkyl, C 3 -C 20 alkenyl, C 3 -C 8 cycloalkyl, cycloalkylalkyl in which the cycloalkyl moiety has from 3 to 8 carbon atoms and the alkyl moiety has from 1 to 6 carbon atoms, phenylalkyl where the alkyl moiety has from 1 to 20 carbon atoms, and substituted phenylalkyl where the phenyl group is substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano, trifluoromethyl, or phenyl; R 2 is H or C 1 -C 6 alkyl, or R 1 and R 2 taken together with the interposed nitrogen forms a heterocyclic group of the formula: ##STR16## where n is one of the integers 0, 1 or 2; X is --S-- or ##STR17## and R 7 is H, hydroxy, C 1 -C 6 alkyl, phenyl or phenyl substituted by C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halo, nitro, cyano or trifluoromethyl; R 8 is H or C 1 -C 6 alkyl; and R 3 , R 4 , R 5 and R 6 are H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano, C 1 -C 6 perhaloalkyl, C 1 -C 16 alkoxycarbonyl or carboxyl.

Claim 5

A compound according to claim 1 which is 4-[[(butylamino)carbonyl]oxy]-1-piperidinecarboxylic acid 4-phenoxyphenyl ester.

Claim 6

A compound according to claim 1 which is 4-[[(hexylamino)carbonyl]oxy]-1-piperidinecarboxylic acid 4-phenoxyphenyl ester.

Claim 7

A compound according to claim 1 which is 4-[[(octylamino)carbonyl]oxy]-1-piperidinecarboxylic acid 4-phenoxyphenyl ester.

Claim 8

A compound according to claim 1 which is 4-[[(cyclohexylamino)carbonyl]oxy]-1-piperidinecarboxylic acid 4-phenoxyphenyl ester.

Claim 9

A compound according to claim 1 which is 4-[[(dodecylamino)carbonyl]oxy]-1-piperidinecarboxylic acid 4-phenoxyphenyl ester.

Claim 10

A compound according to claim 1 which is 4-[[(octadecylamino)carbonyl]oxy]-1-piperidinecarboxylic acid 4-phenoxyphenyl ester.

Claim 11

A compound according to claim 1 which is 4-[[[(1,5-dimethylhexyl)amino]-carbonyl]oxy]-1-piperidinecarboxylic acid 4-phenoxyphenyl ester.

Claim 12

A compound according to claim 1 which is 4-[[(4-methyl-1-piperidinyl)carbonyl]oxy]-1-piperidinecarboxylic acid 4-phenoxyphenyl ester.

Claim 13

A compound according to claim 1 which is 4-[[[[[4-(2,2-dimethylpropyl)phenyl]-methyl]heptylamino]carbonyl]oxy]-1-piperidinecarboxylic acid 4-phenoxyphenyl ester.

Claim 14

A compound according to claim 1 which is 4-[[(methylamino)carbonyl]oxy]-1-piperidinecarboxylic acid 4-phenoxyphenyl ester.

Claim 15

A compound according to claim 1 which is 4-[[(diethylamino)carbonyl]oxy]-1-piperidinecarboxylic acid 4-phenoxyphenyl ester.

Claim 16

A compound according to claim 1 which is 4-[[[(4-phenylbutyl)amino]carbonyl]oxy]-1-piperidinecarboxylic acid 4-phenoxyphenyl ester.

Claim 17

A compound according to claim 1 which is 4-[[(Z)-9-octadecenylamino)carbonyl]oxy]-1-piperidinecarboxylic acid 4-phenoxyphenyl ester.

Claim 18

A compound according to claim 1 which is 4-thiomorpholinecarboxylic acid 1-[(4-phenoxyphenoxy)carbonyl]-4-piperidinyl ester.

Claim 19

A compound according to claim 1 which is 4-phenyl-1-piperidinecarboxylic acid 1-[(4-phenoxyphenoxy)carbonyl]-4-piperidinyl ester.

Claim 20

A compound according to claim 1 which is 4-[[[(cyclohexylmethyl)amino]carbonyl]oxy]-1-piperidinecarboxylic acid 4-phenoxyphenyl ester.

Claim 21

A compound according to claim 1 which is 4-[[(hexylamino)carbonyl]oxy]-1-piperidinecarboxylic acid 4-(4-methylphenoxy)phenyl ester.

Claim 22

A compound according to claim 1 which is 4-[[(hexylamino)carbonyl]oxy]-1-piperidinecarboxylic acid 4-(4-methoxyphenoxy)phenyl ester.

Claim 23

A process for reducing cholesterol absorption in a mammal in need of reduced serum cholesterol levels which comprises internally administering thereto a therapeutically effective amount for lowering serum cholesterol of a compound of the formula: ##STR18## in which R 1 is H, C 1 -C 20 alkyl, C 3 -C 20 alkenyl, C 3 -C 8 cycloalkyl, cycloalkylalkyl where the cycloalkyl moiety has from 3 to 8 carbon atoms and the alkyl moiety has from 1 to 6 carbon atoms, phenyl, phenyl substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano or trifluoromethyl; phenylalkyl where the alkyl moiety has from 1 to 20 carbons, or phenylalkyl where the phenyl group is substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano, trifluoromethyl or phenyl; R 2 is H or C 1 -C 6 alkyl; or R 1 and R 2 taken together with the interposed nitrogen forms a heterocyclic group of the formula: ##STR19## where n is one of the intergers 0, 1 or 2; X is --O--, --S--, or ##STR20## and R 7 is H, hydroxy, C 1 -C 6 alkyl, C 2 -C 6 alkanoyloxy, C 1 -C 6 hydroxyalkyl, carboxyl, C 1 -C 16 alkoxycarbonyl, phenyl or phenyl substituted with C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 perhaloalkyl, halo, nitro or cyano; R 8 is H or C 1 -C 6 alkyl or R 7 and R 8 taken together with the intervening carbon atom forms a polymethylene ring of 3 to 7 carbon atoms; R 9 is H, C 1 -C 6 alkyl or C 2 -C 12 gemdialkyl; and R 3 , R 4 , R 5 and R 6 are H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano, C 1 -C 6 perhaloalkyl, C 1 -C 16 alkoxycarbonyl, or carboxyl.

Claim 24

A process for reducing cholesterol absorption in a mammal in need of reduced serum cholesterol levels which comprises internally administering thereto a therapeutically effective amount for lowering serum cholesterol of a compound of the formula: ##STR18## in which R 1 is H, C 1 -C 20 alkyl, C 3 -C 20 alkenyl, C 3 -C 8 cycloalkyl, cycloalkylalkyl where the cycloalkyl moiety has from 3 to 8 carbon atoms and the alkyl moiety has from 1 to 6 carbon atoms, phenyl, phenyl substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano or trifluoromethyl; phenylalkyl where the alkyl moiety has from 1 to 20 carbons, or phenylalkyl where the phenyl group is substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano, trifluoromethyl or phenyl; R 2 is H or C 1 -C 6 alkyl; or R 1 and R 2 taken together with the interposed nitrogen forms a heterocyclic group of the formula: ##STR19## where n is one of the intergers 0, 1 or 2; X is --O--, --S--, or ##STR20## and R 7 is H, hydroxy, C 1 -C 6 alkyl, C 2 -C 6 alkanoyloxy, C 1 -C 6 hydroxyalkyl, carboxyl, C 1 -C 16 alkoxycarbonyl, phenyl or phenyl substituted with C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 perhaloalkyl, halo, nitro or cyano; R 8 is H or C 1 -C 6 alkyl or R 7 and R 8 taken together with the intervening carbon atom forms a polymethylene ring of 3 to 7 carbon atoms; R 9 is H, C 1 -C 6 alkyl or C 2 -C 12 gemdialkyl; and R 3 , R 4 , R 5 and R 6 are H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano, C 1 -C 6 perhaloalkyl, C 1 -C 16 alkoxycarbonyl, or carboxyl.

Claim 25

A parmaceutical composition for lowering serum cholesterol which comprises: a. a therapeutically effective amount of a compound of the formula: ##STR21## in which R 1 is H, C 1 -C 20 alkyl, C 3 -C 20 alkenyl, C 3 -C 8 cycloalkyl, cycloalkylalkyl where the cycloalkyl moiety has from 3 to 8 carbon atoms and the alkyl moiety has from 1 to 6 carbon atoms, phenyl, phenyl substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano or trifluoromethyl; phenylalkyl where the alkyl moiety has from 1 to 20 carbons, or phenylalkyl where the phenyl group is substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano, trifluoromethyl or phenyl; R 2 is H or C 1 -C 6 alkyl; or R 1 and R 2 taken together with the interposed nitrogen forms a heterocyclic group of the formula: ##STR22## where n is one of the intergers 0, 1 or 2; X is --O--, --S--, or ##STR23## and R 7 is H, hydroxy, C 1 -C 6 alkyl, C 2 -C 6 alkanoyloxy, C 1 -C 6 hydroxyalkyl, carboxyl, C 1 -C 16 alkoxycarbonyl, phenyl or phenyl substituted with C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 perhaloalkyl, halo, nitro or cyano; R 8 is H or C 1 -C 6 alkyl or R 7 and R 8 taken together with the intervening carbon atom forms a polymethylene ring of 3 to 7 carbon atoms; R 9 is H, C 1 -C 6 alkyl or C 2 -C 12 gemdialkyl; R 3 , R 4 , R 5 and R 6 are H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano, C 1 -C 6 perhaloalkyl, C 1 -C 16 alkoxycarbonyl, or carboxyl, and b. a pharmaceutical carrier.

Claim 26

A parmaceutical composition for lowering serum cholesterol which comprises: a. a therapeutically effective amount of a compound of the formula: ##STR21## in which R 1 is H, C 1 -C 20 alkyl, C 3 -C 20 alkenyl, C 3 -C 8 cycloalkyl, cycloalkylalkyl where the cycloalkyl moiety has from 3 to 8 carbon atoms and the alkyl moiety has from 1 to 6 carbon atoms, phenyl, phenyl substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano or trifluoromethyl; phenylalkyl where the alkyl moiety has from 1 to 20 carbons, or phenylalkyl where the phenyl group is substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano, trifluoromethyl or phenyl; R 2 is H or C 1 -C 6 alkyl; or R 1 and R 2 taken together with the interposed nitrogen forms a heterocyclic group of the formula: ##STR22## where n is one of the intergers 0, 1 or 2; X is --O--, --S--, or ##STR23## and R 7 is H, hydroxy, C 1 -C 6 alkyl, C 2 -C 6 alkanoyloxy, C 1 -C 6 hydroxyalkyl, carboxyl, C 1 -C 16 alkoxycarbonyl, phenyl or phenyl substituted with C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 perhaloalkyl, halo, nitro or cyano; R 8 is H or C 1 -C 6 alkyl or R 7 and R 8 taken together with the intervening carbon atom forms a polymethylene ring of 3 to 7 carbon atoms; R 9 is H, C 1 -C 6 alkyl or C 2 -C 12 gemdialkyl; R 3 , R 4 , R 5 and R 6 are H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, nitro, cyano, C 1 -C 6 perhaloalkyl, C 1 -C 16 alkoxycarbonyl, or carboxyl, and b. a pharmaceutical carrier.