US 4,797,411 A · Cycloalkyl-substituted 4-pyridyl derivatives and use as aromatase inhibitors

Abstract

The invention relates to cycloalkyl-substituted 4-pyridyl derivatives of formula (I) ##STR1## wherein R is C.sub.1 -C.sub.4 alkyl; each of R.sub.1 and R.sub.2 is, independently, hydrogen or C.sub.1 -C.sub.4 alkyl; n is an integer of 1 to 5; and either (a) A is >C.dbd.O and B is --O--, --NH-- or --CH.sub.2 --; or (b) A is --CH.sub.2 --and B is --O--, --NH--, --CH.sub.2 -- or >C.dbd.O; or (c) A is --O-- and B is >C.dbd.O or --CH.sub.2 --; or (d) A is --NH-- and B is >C.dbd.O or --CH.sub.2 --, and their pharmaceutically acceptable salts. The compounds of the invention show aromatase inhibiting activity and can be useful, e.g., in treating hormone-dependent tumors and prostatic hyperplasia.

Claims17

Dependent claims

A cycloalkyl-substituted 4-pyridyl derivative of formula (I) ##STR10## wherein R is C.sub.1 -C.sub.4 alkyl;

each of R.sub.1 and R.sub.2 is, independently, hydrogen or C.sub.1 -C.sub.4 alkyl;
n is an integer of 1 to 5;
and either
(a) A is >C.dbd.O and B is --O--, --NH-- or --CH.sub.2 --;
or
(b) A is --CH.sub.2 -- and B is --O--, --NH--, --CH.sub.2 -- or >C.dbd.O;
or
(c) A is --O-- and B is >C.dbd.O or --CH.sub.2 --;
or
(d) A is --NH-- and B is >C.dbd.O or --CH.sub.2 --,
and the pharmaceutically acceptable salts thereof.

8 more elements

A compound, either as single enantiomer or as racemic mixture, selected from the group consisting of:

cyclohexyl 2-(4'-pyridyl)propionate;
cyclohexyl 2-(2'-methylpyrid-4'-yl)propionate;
cyclohexyl 2-(3-methylpyrid-4'-yl)propionate;
cyclohexyl 2-(2',6'-dimethylpyrid-4'-yl)propionate;
cyclohexyl 2-(2',5'-dimethylpyrid-4'-yl)propionate;
cyclohexyl 2-(2',3'-dimethylpyrid-4'-yl)propionate;
cyclohexyl 2-(3',5'-dimethylpyrid-4'-yl)propionate;
N-cyclohexyl-2-(4'-pyridyl)propanamide;
N-cyclohexyl-2-(2'-methylpyrid-4'-yl)propanamide;
N-cyclohexyl-2-(3'-methylpyrid-4'-yl)propanamide;
N-cyclohexyl-2-(2',6'-dimethylpyrid-4'-yl)propanamide;
N-cyclohexyl-2-(2',5'-dimethylpyrid-4'-yl)propanamide;
N-cyclohexyl-2-(2',3'-dimethylpyrid-4'-yl)propanamide;
N-cyclohexyl-2-(3',5'-dimethylpyrid-4'-yl)propanamide;
2-(4'-pyridyl)propylcyclohexyl ether;
2-(2'-methylpyrid-4'-yl)propylcyclohexyl ether;
2-(3'-methylpyrid-4'-yl)propylcyclohexyl ether;
2-(2',6'-dimethylpyrid-4'-yl)propylcyclohexyl ether;
2-(2',5'-dimethylpyrid-4'-yl)propylcyclohexyl ether;
2-(2',3'-dimethylpyrid-4'-yl)propylcyclohexyl ether;
2-(3',5'-dimethylpyrid-4'-yl)propylcyclohexyl ether;
N-cyclohexyl-2-(4'-pyridyl)propylamine;
N-cyclohexyl-2-(2'-methylpyrid-4'-yl)propylamine;
N-cyclohexyl-2-(3'-methylpyrid-4-yl)propylamine;
N-cyclohexyl-2-(2',6'-dimethylpyrid-4'-yl)propylamine;
N-cyclohexyl-2-(2',5'-dimethylpyrid-4'-yl)propylamine;
N-cyclohexyl-2-(2',3'-dimethylpyrid-4'-yl)propylamine;
N-cyclohexyl-2-(3',5'-dimethylpyrid-4'-yl)propylamine;
1-cyclohexyl-3-(4'-pyridyl)-2-butanone;
1-cyclohexyl-3-(2'-methylpyrid-4'-yl)-2-butanone;
1-cyclohexyl-3-(3'-methylpyrid-4'-yl)-2-butanone;
1-cyclohexyl-3-(2',6'-dimethylpyrid-4'-yl)-2-butanone;
1-cyclohexyl-3-(2',5'-dimethylpyrid-4'-yl)-2-butanone;
1-cyclohexyl-3-(2',3'-dimethylpyrid-4'-yl)-2-butanone;
1-cyclohexyl-3-(3',5'-dimethylpyrid-4'-yl)-2-butanone;
1-cyclohexyl-3-(4'-pyridyl)butane;
1-cyclohexyl-3-(2'-methylpyrid-4'-yl)butane;
1-cyclohexyl-3-(3'-methylpyrid-4'-yl)butane;
1-cyclohexyl-3-(2',6'-dimethylpyrid-4'-yl)butane;
1-cyclohexyl-3-(2',5'-dimethylpyrid-4'-yl)butane;
1-cyclohexyl-3-(2',3'-dimethylpyrid-4'-yl)butane;
1-cyclohexyl-3-(3',5'-dimethylpyrid-4'-yl)butane;
1-(4'-pyridyl)ethyl cyclohexanecarboxylate;
1-(2'-methylpyrid-4'-yl)ethyl cyclohexanecarboxylate;
1-(3'-methylpyrid-4'-yl)ethyl cyclohexanecarboxylate;
1-(2',6'-dimethylpyrid-4'-yl)ethyl cyclohexanecarboxylate;
1-(2',5'-dimethylpyrid-4'-yl)ethyl cyclohexanecarboxylate;
1-(2',3'-dimethylpyrid-4'-yl)ethyl cyclohexanecarboxylate;
1-(3',5'-dimethylpyrid-4'-yl)ethyl cyclohexanecarboxylate;
1-(4'-pyridyl)ethyl cyclohexylmethyl ether;
1-(2'-methylpyrid-4'-yl)ethyl cyclohexylmethyl ether;
1-(3'-methylpyrid-4'-yl)ethyl cyclohexylmethyl ether;
1-(2',6'-dimethylpyrid-4'-yl)ethyl cyclohexylmethyl ether;
1-(2',5'-dimethylpyrid-4'-yl)ethyl cyclohexylmethyl ether;
1-(2',3'-dimethylpyrid-4'-yl)ethyl cyclohexylmethyl ether;
1-(3',5'-dimethylpyrid-4'-yl)ethyl cyclohexylmethyl ether;
N-[1-(4'-pyridyl)ethyl]cyclohexanecarboxyamide;
N-[1-(2'-methylpyrid-4'-yl)ethyl]cyclohexanecarboxyamide;
N-[1-(3'-methylpyrid-4'-yl)ethyl]cyclohexanecarboxyamide;
N-[1-(2',6'-dimethylpyrid-4'-yl)ethyl]cyclohexanecarboxyamide;
N-[1-(2',5'-dimethylpyrid-4'-yl)ethyl]cyclohexanecarboxyamide;
N-[1-(2',3'-dimethylpyrid-4'-yl)ethyl]cyclohexanecarboxyamide;
N-[1-(3',5'-dimethylpyrid-4'-yl)ethyl]cyclohexanecarboxyamide;
N-[1-(4'-pyridyl)ethyl]cyclohexylmethylamine;
N-[1-(2'-methylpyrid-4'-yl)ethyl]cyclohexylmethylamine;
N-[1-(3'-methylpyrid-4'-yl)ethyl]cyclohexylmethylamine;
N-[1-(2',6'-dimethylpyrid-4'-yl)ethyl]cyclohexylmethylamine;
N-[1-(2',5'-dimethylpyrid-4'-yl)ethyl]cyclohexylmethylamine;
N-[1-(2',3'-dimethylpyrid-4'-yl)ethyl]cyclohexylmethylamine;
N-[1-(3',5'-dimethylpyrid-4'-yl)ethyl]cyclohexylmethylamine;
2-(4'-pyridyl)propylcyclohexylketone;
2-(2'-methylpyrid-4'-yl)propylcyclohexylketone;
2-(3'-methylpyrid-4'-yl)propylcyclohexylketone;
2-(2',6'-dimethylpyrid-4'-yl)propylcyclohexylketone;
2-(2',5'-dimethylpyrid-4'-yl)propylcyclohexylketone;
2-(2',3'-dimethylpyrid-4'-yl)propylcyclohexylketone;
2-(3',5'-dimethylpyrid-4'-yl)propylcyclohexylketone;
and the pharmaceutically acceptable salts thereof.

75 more elements

A compound, either as single enantiomer or as racemic mixture, selcted from the group consisting of:

cyclohexyl 2-(4'-pyridyl)propionate;
cyclohexyl 2-(2'-methylpyrid-4'-yl)propionate;
cyclohexyl 2-(3'-methylpyrid-4'-yl)propionate;
cyclohexyl 2-(2',6'-dimethylpyrid-4'-yl)propionate;
cyclohexyl 2-(2',5'-dimethylpyrid-4'-yl)propionate;
cyclohexyl 2-(2',3'-dimethylpyrid-4'-yl)propionate;
cyclohexyl 2-(3',5'-dimethylpyrid-4'-yl)propionate;
N-cycohexyl-2-(4'-pyridyl)propanamide;
N-cyclohexyl-2-(2'-methylpyrid-4'-yl)propanamide;
N-cyclohexyl-2-(3'-methylpyrid-4'-yl)propanamide;
N-cyclohexyl-2-(2',6'-dimethylpyrid-4'-yl)propanamide;
N-cyclohexyl-2-(2',5'-dimethylpyrid-4'-yl)propanamide;
N-cyclohexyl-2-(2',3'-dimethylpyrid-4'-yl)propanamide;
N-cyclohexyl-2-(3',5'-dimethylpyrid-4'-yl)propanamide;
2-(4'-pyridyl)propylcyclohexyl ether;
2-(2'-methylpyrid-4'-yl)propylcyclohexyl ether;
2-(3'-methylpyrid-4'-yl)propylcyclohexyl ether;
2-(2',6'-dimethylpyrid-4'-yl)propylcyclohexyl ether;
2-(2',5'-dimethylpyrid-4'-yl)propylcyclohexyl ether;
2-(2',3'-dimethylpyrid-4'-yl)propylcyclohexyl ether;
2-(3',5'-dimethylpyrid-4'-yl)propylcyclohexyl ether;
N-cyclohexyl-2-(4'-pyridyl)propylamine;
N-cyclohexyl-2-(2'-methylpyrid-4'-yl)propylamine;
N-cyclohexyl-2-(3'-methylpyrid-4'-yl)propylamine;
N-cyclohexyl-2-(2',6'-dimethylpyrid-4'-yl)propylamine;
N-cyclohexyl-2-(2',5'-dimethylpyrid-4'-yl)propylamine;
N-cyclohexyl-2-(2',3'-dimethylpyrid-4'-yl)propylamine;
N-cyclohexyl-2-(3',5'-dimethylpyrid-4'-yl)propylamine;
1-cyclohexyl-3-(4'-pyridyl)-2-butanone;
1-cyclohexyl-3-(2'-methylpyrid-4'-yl)-2-butanone;
1-cyclohexyl-3-(3'-methylpyrid-4'-yl)-2-butanone;
1-cyclohexyl-3-(2',6'-dimethylpyrid-4'-yl)-2-butanone;
1-cyclohexyl-3-(2',5'-dimethylpyrid-4'-yl)-2-butanone;
1-cyclohexyl-3-(2',3'-dimethylpyrid-4'-yl)-2-butanone;
1-cyclohexyl-3-(3',5'-dimethylpyrid-4'-yl)-2-butanone;
1-cyclohexyl-3-(4'-pyridyl)butane;
1-cyclohexyl-3-(2'-methylpyrid-4'-yl)butane;
1-cyclohexyl-3-(3'-methylpyrid-4'-yl)butane;
1-cyclohexyl-3-(2',6'-dimethylpyrid-4'-yl)butane;
1-cyclohexyl-3-(2',5'-dimethylpyrid-4'-yl)butane;
1-cyclohexyl-3-(2',3'-dimethylpyrid-4'-yl)butane;
1-cyclohexyl-3-(3',5'-dimethylpyrid-4'-yl)butane,
and the pharmaceutically acceptable salts thereof.

40 more elements

Dependencies are inferred from the claim text.

Cycloalkyl-substituted 4-pyridyl derivatives and use as aromatase inhibitors

Life of this patent

Cycloalkyl-substituted 4-pyridyl derivatives and use as aromatase inhibitors

Life of this patent

Abstract

Claims17