N-sulfonylurea apoptosis promoters
Compounds having the formula are apoptosis promoters. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
1. A compound of formula (I)
or a therapeutically acceptable salt thereof, wherein
A is piperazine;
R 1 is nitro;
R 2 is —NR 5 R 6 ;
R 3 is hydrogen;
R 4 is selected from the group consisting of aryl and cycloalkyl wherein the aryl group may be optionally substituted with up to 5 substituents selected from the group consisting of alkyl, nitro, halo, phenylalkoxy, morpholinocarbonylalkyl and morpholinoalkyl and the cycloalkyl group may be optionally substituted with up to 5 substituents selected from the group consisting of alkyl, alkoxy and phenylalkyl;
R 5 is hydrogen and R 6 is selected from the group consisting of, arylsulfanylalkyl, arylsulfinylalkyl and arylsulfonylalkyl, the alkyl part of each of which is substituted with —NR 9 R 10 , wherein R 9 and R 10 are alkyl; and
R 15 is selected from the group consisting of hydrogen, alkoxy, alkyl, and halo.
2. The compound of claim 1 wherein R 4 is cycloalkyl.
3. The compound of claim 2 selected from the group consisting of
N-{[4-({(1R)-5-(dimethylamino)-1-[(phenylthio)methyl]pentyl}amino)-3-nitrophenyl]sulfonyl}-4-(4,4-dimethylcyclohexyl)piperazine-1-carboxamide;
N-{[4-({(1R)-3 -(dimethylamino)-1-[(phenylthio)methyl]propyl}amino)-3-nitrophenyl]sulfonyl}-4-(4,4-dimethylcyclohexyl)piperazine-1-carboxamide; and
4-(4-benzyl-4-methoxycyclohexyl)-N-{[4-({(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl}amino)-3-nitrophenyl]sulfonyl}piperazine-1-carboxamide.
4. The compound of claim 1 wherein R 4 is aryl.
5. The compound of claim 4 selected from the group consisting of
N-{[4-({(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl}amino)-3-nitrophenyl]sulfonyl}-4-phenylpiperazine-1-carboxamide;
N-{[4-({(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl}amino)-3-nitrophenyl[sulfonyl}-4-(4-nitrophenyl)piperazine-1-carboxamide;
4-[4-(benzyloxy)phenyl]-N-{[4-({(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl}amino)-3-nitrophenyl]sulfonyl}piperazine-1-carboxamide;
N-{[4-({(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl}amino)-3-nitrophenyl]sulfonyl}-4-[4-(3-morpholin-4-yl-3-oxopropyl)phenyl]piperazine-1-carboxamide; and
N-{[4-({(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl}amino)-3-nitrophenyl]sulfonyl}-4-[4-(3-morpholin-4-ylpropyl)phenyl]piperazine-1-carboxamide.
6. A pharmaceutical composition comprising a compound of claim 1 or a therapeutically acceptable salt thereof, in combination with a therapeutically acceptable carrier.