IP Library › Granted Patent US 7,585,858
Granted Patent B2
US 7,585,858 · App. 11/138,717 · Granted Sep 8, 2009

N-sulfonylcarboximidamide apoptosis promoters

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Quick Facts
Patent No.
US 7,585,858
App. No.
11/138,717
Granted
Sep 8, 2009
Kind
B2
Abstract

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.

Claims (35)

1. A compound of formula (I)

or a therapeutically acceptable salt thereof, wherein

A is phenyl;

R 1 is selected from the group consisting of alkyl, cyano, halo, haloalkyl and nitro;

R 2 is —NR 5 R 6 ;

R 3 is hydrogen;

R 4 is piperidinyl;

R 5 is hydrogen and and R 6 is arylsulfanylalkyl, the alkyl part of which can be further optionally substituted with morpholinyl or NR a R b , wherein R a and R b 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 15 is hydrogen.

3. A compound selected from the group consisting of

N-((4-((( 1R)-3 -(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)-4-(4-(2-fluorobenzyl)-4-methoxy-1-piperidinyl)benzenecarboximidamide;

N-((4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)-4-(4,4-dimethyl-1-piperidinyl)benzenecarboximidamide;

N((4-(((1R)-5 -(dimethylamino)- 1-(phenylsulfanyl)methyl)pentyl)amino)-3-nitrophenyl)sulfonyl)-4-(4,4-dimethyl-1-piperidinyl)benzenecarboximidamide;

4-(4,4-dimethyl-1-piperidinyl)-N-((3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)phenyl)sulfonyl)benzenecarboximidamide;

4-(4-benzyl-4-methoxy-1-piperidinyl)-N-((4-(((1R)-3-(dimethylamino)- 1 -((phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)benzenecarboximidamide;

4-(4-(cyclohexylmethyl)-4-methoxy- 1-piperidinyl)-N-((4-(((1R)-3-(dimethylamino)- 1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)benzenccarboximidamide;

4-(4-(2,4-difluorobenzyl)-4-methoxy-1-piperidinyl)-N-((4-((( 1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)benzenecarboximidamide;

N-((4(((1R)-3-(dimethylamino)- 1-(phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)-4-(4-methoxy-4-(2-methylbenzyl)-1-piperidinyl)benzenecarboximidamide;

N-((4-(((1R)-3-(dimethylamino)-1-(phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)-4-(4-(4-fluorobenzylidene)-1-piperidinyl)benzenecarboximidamide;

N-((4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)-4-(4-(2-(trifluoromethyl)benzylidene)-1-piperidinyl)benzenecarboximidamide;

N-((4-(((1R)-3-(dimethylamino)- 1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)-4-(4-(3-thienylmethylene)-1-piperidinyl)benzenecarboximidamide;

4-(4-methoxy-4-(2-methylbenzyl)- 1-piperidinyl)-N-((3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)phenyl)sulfonyl)benzenecarboximidamide;

N-((4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-3-nitrophenyl)sulfonyl)-4-(4-methoxy-4-(2-methylbenzyl)-1-piperidinyl)benzenecarboximidamide;

4-(4-methoxy-4-(2-methylbenzyl)- 1-piperidinyl)-N-((4-(((1R)-3-(4-morpholinyl) 1((phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)benzenecarboximidamide;

4-(4-(1,1′-biphenyl-2-ylmethyl)-4-methoxy-1-piperidinyl)-N-((3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)phenyl)sulfonyl)benzenecarboximidamide;

4-(4-(1,1′-biphenyl-2-ylmethyl)-4-methoxy-1-piperidinyl)-N-((4-((1,1-dimethyl -2-(phenylsulfanyl)ethyl)amino)-3-nitrophenyl)sulfonyl)benzenecarboximidamide;

4-(4-(1,1′-biphenyl-2-ylmethyl)-4-methoxy-1-piperidinyl)-N-((4-(((1R)-3-(4-morpholinyl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)benzenecarboximidamide;

4-(4-(1,1′-biphenyl-2-ylmethylene)-1-piperidinyl)-N′-((3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)phenyl)sulfonyl)benzenecarboximidamide;

4-(4-(1,1′-biphenyl-2-ylmethylene)-1-piperidinyl)-N′-((4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-3 -nitrophenyl)sulfonyl)benzenecarboximidamide;

4-(4-(1,1′-biphenyl-2-ylmethylene)-1-piperidinyl)-N′-((4-(((1R)-3-(4-morpholinyl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)benzenecarboximidamide;

N′-((3-nitro-4-((2-(phenylsulfanyl)ethyl)amino)phenyl)sulfonyl)-4-(4-(2-(trifluoromethyl)benzylidene)-1-piperidinyl)benzenecarboximidamide;

N′-((4-((1,1-dimethyl-2-(phenylsulfanyl)ethyl)amino)-3-nitrophenyl)sulfonyl)-4-(4-(2-(trifluoromethyl)benzylidene)-1-piperidinyl)benzenecarboximidamide; and

N′-((4-(((1R)-3-(4-morpholinyl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrophenyl)sulfonyl)-4-(4-(2-(trifluoromethyl,)benzylidene)-1-piperidinyl)benzenecarboximidamide.

4. A pharmaceutical composition comprising a compound of claim 1 or a therapeutically acceptable salt thereof, in combination with a therapeutically acceptable carrier.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 9, 2013
From: ABBOTT LABORATORIES
To: ABBVIE INC.
Reel/Frame 030182/0547 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 24, 2006
From: ELMORE, STEVEN W.; BRUNCKO, MILAN; PARK, CHEOL-MIN
To: ABBOTT LABORATORIES
Reel/Frame 017287/0128 →