US 2007/0191479 A1Published application

Aniline derivatives as selective androgen receptor modulators

AssigneeSmithKline Beecham Corporation

InventorsPhilip Turnbull, Rodolfo Cadilla, David Cowan, Andrew Larkin, Istvan Kaldor, Eugene Stewart

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Abstract

This invention relates to non-steroidal compounds that are modulators of androgen, glucocorticoid, mineralocorticoid, and progesterone receptors, and also to the methods for the making and use of such compounds.

Claims23

Dependent claims

A compound of formula (I)

including salts, solvates, and physiologically functional derivatives thereof,
wherein
R1 is -(Q1)x-R5;
Q1 is alkylene;
x is 0 or 1;
R5 is H, alkyl, alkenyl, alkynyl, haloalkyl, or cycloalkyl;
R2 is (Q3)-(Q4)-R6, or -(Q3)-CN;
Q3 is alkylene;
Q4 is —C(O)—, —C(S)—, or —C(NR7)—,
R7 is H or alkyl;
R6 is alkyl, alkenyl, alkynyl, hydroxy, alkoxy, aryloxy, or —N(R8)(R9)
R8 and R9 each independently are H, hydroxy, alkyl, alkenyl, alkynyl, -(Q5)y-cycloalkyl, —N(R10)(R11), or R8 and R9 combine with the nitrogen atom to which they are attached to form an optionally substituted 4 to 8 membered ring that may contain additional heteroatoms and may contain one or more degrees of unsaturation;
Q5 is alkylene;
y is 0 or 1;
R10 and R11 each independently are H or alkyl;
R3 is —CN, —NO2, or halogen;
and
R4 is —CN, —NO2, halogen, haloalkyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, aryl, aryloxy.

15 more elements

A compound selected from:

1,1-dimethylethyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(cyclopropylmethyl)glycinate;
N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(cyclopropylmethyl)glycine;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(cyclopropylmethyl)-N1-methylglycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(cyclopropylmethyl)glycinamide;
1,1-dimethylethyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-methylglycinate;
1,1-dimethylethyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-ethylglycinate;
N-[4-cyano-3-(trifluoromethyl)phenyl]-N-ethylglycine;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-ethylglycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-ethyl-N1-propylglycinamide,
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N1-(cyclopropylmethyl)-N2-ethylglycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-ethyl-N1,N1-dipropylglycinamide;
1,1-dimethylethyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,2,2-trifluoroethyl)glycinate;
N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,2,2-trifluoroethyl)glycine;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(2,2,2-trifluoroethyl)glycinamide;
methyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,2,2-trifluoroethyl)glycinate;
1-methylethyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,2,2-trifluoroethyl)glycinate;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N1-methyl-N2-(2,2,2-trifluoroethyl)glycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N1-ethyl-N2-(2,2,2-trifluoroethyl)glycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N1-cyclohexyl-N2-(2,2,2-trifluoroethyl)glycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N1,N1-dimethyl-N2-(2,2,2-trifluoroethyl)glycinamide;
2-[4-cyano(2,2,2-trifluoroethyl)-3-(trifluoromethyl)anilino]-N-methylacetohydrazide;
2-[4-cyano(2,2,2-trifluoroethyl)-3-(trifluoromethyl)anilino]-N′,N′-dimethylacetohydrazide;
methyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,2,2-trifluoroethyl)alaninate;
N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,2,2-trifluoroethyl)alanine;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(2,2,2-trifluoroethyl)alaninamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-methyl-N2-(2,2,2-trifluoroethyl)alaninamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N1-ethyl-N2-(2,2,2-trifluoroethyl)alaninamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N1,N1-dimethyl-N2-(2,2,2-trifluoroethyl)alaninamide;
1,1-dimethylethyl 2-[[4-cyano-3-(trifluoromethyl)phenyl](2,2,2-trifluoroethyl)amino]butanoate;
2-[[4-cyano-3-(trifluoromethyl)phenyl](2,2,2-trifluoroethyl)amino]butanoic acid;
2-[[4-cyano-3-(trifluoromethyl)phenyl](2,2,2-trifluoroethyl)amino]butanamide;
2-[[4-cyano-3-(trifluoromethyl)phenyl](2,2,2-trifluoroethyl)amino]-N-methylbutanamide;
2-[[4-cyano-3-(trifluoromethyl)phenyl](2,2,2-trifluoroethyl)amino]-N-ethylbutanamide;
2-[[4-cyano-3-(trifluoromethylphenyl](2,2,2-trifluoroethyl)amino]-N,N-dimethylbutanamide;
1,1-dimethylethyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-propylglycinate;
N-[4-cyano-3-(trifluoromethyl)phenyl]-N-propylglycine;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-propylglycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N1,N2-dipropylglycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N1-(cyclopropylmethyl)-N2-propylglycinamide;
1,1-dimethylethyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-2-propen-1-ylglycinate;
methyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2-fluoroethyl)glycinate;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(2-fluoroethyl)glycinamide;
1,1-dimethylethyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2-methylpropyl)glycinate;
N-[4-cyano-3-(trifluoromethyl)phenyl]-N-isobutylglycine;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-isobutylglycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-isobutyl-N1-methylglycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(cyclopropylmethyl)-N1-ethylglycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N1,N2-bis(cyclopropylmethyl)glycinamide;
1,1-dimethylethyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(cyclopropylmethyl)alaninate;
N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(cyclopropylmethyl)alanine;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(cyclopropylmethyl)alaninamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(cyclopropylmethyl)-N1-methylalaninamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(cyclopropylmethyl)-N1-ethylalaninamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(cyclopropylmethyl)-N1,N1-dimethylalaninamide;
4-[(cyanomethyl)(2,2,2-trifluoroethyl)amino]-2-(trifluoromethyl)benzonitrile;
4-[(1-cyanoethyl)(2,2,2-trifluoroethyl)amino]-2-(trifluoromethyl)benzonitrile;
methyl 3-[[4-cyano-3-(trifluoromethyl)phenyl](2,2,2-trifluoroethyl)amino]-2-methylpropanoate;
4-[(2-cyanopropyl)(2,2,2-trifluoroethyl)amino]-2-(trifluoromethyl)benzonitrile;
N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,2-dimethylpropyl)glycine;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(2,2-dimethylpropyl)glycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(2,2,2-trifluoro-1-methylethyl)glycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-[1-(trifluoromethyl)propyl]glycinamide,
1,1-dimethylethyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(3,3,3-trifluoropropyl)glycinate;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(3,3,3-trifluoropropyl)glycinamide;
4-[(cyanomethyl)(3,3,3-trifluoropropyl)amino]-2-(trifluoromethyl)benzonitrile;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(3,3,3-trifluoropropyl)alaninamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N1-methyl-N2-(3,3,3-trifluoropropyl)alaninamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(1,1-dimethylethyl)glycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N2-(1-methylethyl)glycinamide;
N2-[4-cyano-3-(trifluoromethyl)phenyl]-N1-methyl-N2-(1-methylethyl)glycinamide;
4-[(cyanomethyl)(methyl)amino]-2-(trifluoromethyl)benzonitrile;
4-[(2-cyanoethyl)(methyl)amino]-2-(trifluoromethyl)benzonitrile;
1,1-dimethylethyl N-(3-chloro-4-cyanophenyl)-N-(2,2,2-trifluoroethyl)glycinate;
N-(3-chloro-4-cyanophenyl)-N-(2,2,2-trifluoroethyl)glycine;
N2-(3-chloro-4-cyanophenyl)-N2-(2,2,2-trifluoroethyl)glycinamide;
N2-(3-chloro-4-cyanophenyl)-N1-methyl-N2-(2,2,2-trifluoroethyl)glycinamide;
N2-(3-chloro-4-cyanophenyl)-N1-ethyl-N2-(2,2,2-trifluoroethyl)glycinamide;
1,1-dimethylethyl N-(3-chloro-4-cyanophenyl)-N-(2,2,2-trifluoroethyl)alaninate;
N-(3-chloro-4-cyanophenyl)-N-(2,2,2-trifluoroethyl)alanine;
N2-(3-chloro-4-cyanophenyl)-N2-(2,2,2-trifluoroethyl)alaninamide;
N2-(3-chloro-4-cyanophenyl)-N1-methyl-N2-(2,2,2-trifluoroethyl)alaninamide;
N2-(3-chloro-4-cyanophenyl)-N1-ethyl-N2-(2,2,2-trifluoroethyl)alaninamide;
1,1-dimethylethyl 2-[(3-chloro-4-cyanophenyl)(2,2,2-trifluoroethyl)amino]butanoate;
2-[(3-chloro-4-cyanophenyl)(2,2,2-trifluoroethyl)amino]butanamide;
2-[(3-chloro-4-cyanophenyl)(2,2,2-trifluoroethyl)amino]-N-methylbutanamide;
2-[(3-chloro-4-cyanophenyl)(2,2,2-trifluoroethyl)amino]-N-ethylbutanamide;
1,1-dimethylethyl N-(3-chloro-4-cyanophenyl)-N-(cyclopropylmethyl)glycinate;
N-(3-chloro-4-cyanophenyl)-N-(cyclopropylmethyl)glycine;
N2-(3-chloro-4-cyanophenyl)-N2-(cyclopropylmethyl)glycinamide;
N2-(3-chloro-4-cyanophenyl)-N2-(cyclopropylmethyl)-N1-methylglycinamide;
N2-(3-chloro-4-cyanophenyl)-N2-(cyclopropylmethyl)-N1-ethylglycinamide;
2-chloro-4-[(cyanomethyl)(cyclopropylmethyl)amino]benzonitrile;
1,1-dimethylethyl N-(3-chloro-4-cyanophenyl)-N-(cyclopropylmethyl)alaninate;
N-(3-chloro-4-cyanophenyl)-N-(cyclopropylmethyl)alanine;
N2-(3-chloro-4-cyanophenyl)-N2-(cyclopropylmethyl)alaninamide;
N2-(3-chloro-4-cyanophenyl)-N2-(cyclopropylmethyl)-N1-methylalaninamide;
N2-(3-chloro-4-cyanophenyl)-N2-(cyclopropylmethyl)-N1-ethylalaninamide;
1,1-dimethylethyl 2-[(3-chloro-4-cyanophenyl)(cyclopropylmethyl)amino]butanoate;
2-[(3-chloro-4-cyanophenyl)(cyclopropylmethyl)amino]butanoic acid;
2-[(3-chloro-4-cyanophenyl)(cyclopropylmethyl)amino]butanamide;
2-[(3-chloro-4-cyanophenyl)(cyclopropylmethyl)amino]-N-methylbutanamide;
2-[(3-chloro-4-cyanophenyl)(cyclopropylmethyl)amino]-N-ethylbutanamide;
methyl N-(3,4-dicyanophenyl)-N-(2,2,2-trifluoroethyl)glycinate;
1,1-dimethylethyl N-(3,4-dicyanophenyl)-N-(2,2,2-trifluoroethyl)glycinate;
N2-(3,4-dicyanophenyl)-N2-(2,2,2-trifluoroethyl)glycinamide;
N2-(3,4-dicyanophenyl)-N1-methyl-N2-(2,2,2-trifluoroethylglycinamide;
N2-(3,4-dicyanophenyl)-N1-ethyl-N2-(2,2,2-trifluoroethyl)glycinamide;
1,1-dimethylethyl N-(3,4-dicyanophenyl)-N-(2,2,2-trifluoroethyl)alaninate;
N-(3,4-dicyanophenyl)-N-(2,2,2-trifluoroethyl)alanine;
N2-(3,4-dicyanophenyl)-N2-(2,2,2-trifluoroethyl)alaninamide;
N2-(3,4-dicyanophenyl)-N1-methyl-N2-(2,2,2-trifluoroethyl)alaninamide;
N2-(3,4-dicyanophenyl)-N1-ethyl-N2-(2,2,2-trifluoroethyl)alaninamide;
1,1-dimethylethyl 2-[(3,4-dicyanophenyl)(2,2,2-trifluoroethyl)amino]butanoate;
2-[(3,4-dicyanophenyl)(2,2,2-trifluoroethyl)amino]butanoic acid;
2-[(3,4-dicyanophenyl)(2,2,2-trifluoroethyl)amino]butanamide;
2-[(3,4-dicyanophenyl)(2,2,2-trifluoroethylamino]-N-methylbutanamide;
2-[(3,4-dicyanophenyl)(2,2,2-trifluoroethyl)amino]-N-ethylbutanamide;
1,1-dimethylethyl N-(cyclopropylmethyl)-N-(3,4-dicyanophenyl)glycinate;
N-(cyclopropylmethyl)-N-(3,4-dicyanophenyl)glycine;
N2-(cyclopropylmethyl)-N2-(3,4-dicyanophenyl)glycinamide;
N2-(cyclopropylmethyl)-N2-(3,4-dicyanophenyl)-N1-methylglycinamide;
N2-(cyclopropylmethyl)-N2-(3,4-dicyanophenyl)-N1-ethylglycinamide;
4-[(cyanomethyl)(cyclopropylmethyl)amino]-1,2-benzenedicarbonitrile;
1,1-dimethylethyl N-(cyclopropylmethyl)-N-(3,4-dicyanophenyl)alaninate;
N-(cyclopropylmethyl)-N-(3,4-dicyanophenyl)alanine;
N2-(cyclopropylmethyl)-N2-(3,4-dicyanophenyl)-N1-methylalaninamide;
N2-(cyclopropylmethyl)-N2-(3,4-dicyanophenyl)-N1-methylalaninamide;
N2-(cyclopropylmethyl)-N2-(3,4-dicyanophenyl)-N1-ethylalaninamide;
1,1-dimethylethyl 2-[(cyclopropylmethyl)(3,4-dicyanophenyl)amino]butanoate;
2-[(cyclopropylmethyl)(3,4-dicyanophenyl)amino]butanoic acid;
2-[(cyclopropylmethyl)(3,4-dicyanophenyl)amino]butanamide;
2-[(cyclopropylmethyl)(3,4-dicyanophenyl)amino]-N-methylbutanamide;
and 2-[(cyclopropylmethyl)(3,4-dicyanophenyl)amino]-N-ethylbutanamide.

130 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/598,508Filed 3 Mar 2005
Priority: 3 Mar 2004
Published: 16 Aug 2007
Term ends: Not estimatedThe source records don’t support an estimate.

Classification17 codes

C07C 255/58
Having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton: containing cyano groups and singly-bound nitrogen…
A61P 3/06
Drugs for disorders of the metabolism: antihyperlipidemics
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…

Family

Application60/549,794Us provisional application · filed 3 Mar 2004
US 7,514,470 B2Related patent
US 2007/0191479 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

Facts

Application

10/598,508Filed 3 Mar 2005

Priority

3 Mar 2004

Published

16 Aug 2007

Term ends

Not estimatedThe source records don’t support an estimate.

Classification17 codes

C07C 255/58
Having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton: containing cyano groups and singly-bound nitrogen…
A61P 3/06
Drugs for disorders of the metabolism: antihyperlipidemics
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…