IP Library › Granted Patent US 7,825,120
Granted Patent B2
US 7,825,120 · App. 11/639,398 · Granted Nov 2, 2010

Certain substituted ((piperazin-1-ylmethyl)benzyl)ureas

Assignee: Cytokinetics, Inc.
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Quick Facts
Patent No.
US 7,825,120
App. No.
11/639,398
Granted
Nov 2, 2010
Kind
B2
Abstract

Certain substituted ((piperazin-1-ylmethyl)benzyl)urea derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and may be useful in the treatment of systolic heart failure including congestive heart failure.

Claims (83)

1. A compound chosen from

tert-butyl 4-{[3-({[(6-methyl-3-pyridyl)amino]carbonylamino}methyl)phenyl]methyl}-piperazinecarboxylate;

methyl 4-{[3-({[(6-methyl-3-pyridyl)amino]carbonylamino}methyl)phenyl]methyl}-piperazinecarboxylate;

N-[(3-{[4-(ethylsulfonyl)piperazinyl]methyl}phenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-({3-[(4-acetylpiperazinyl)methyl]phenyl}methyl)[(6-methyl(3-pyridyl))amino]carboxamide;

N-{[3-({4-[(dimethylamino)sulfonyl]piperazinyl}methyl)phenyl]methyl}[(6-methyl(3-pyridyl))amino]carboxamide;

tert-butyl 4-{[4-fluoro-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}methyl)phenyl]-methyl}piperazinecarboxylate;

methyl 4-{[4-fluoro-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}methyl)phenyl]-methyl}piperazinecarboxylate;

ethyl 4-{[4-fluoro-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}methyl)phenyl]-methyl}piperazinecarboxylate;

N-({5-[(4-acetylpiperazinyl)methyl]-2-fluorophenyl}methyl)[(6-methyl(3-pyridyl))amino]carboxamide;

N-[(5-{[4-(N,N-dimethylcarbamoyl)piperazinyl]methyl}-2-fluorophenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-[(5-{[4-(ethylsulfonyl)piperazinyl]methyl}-2-fluorophenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-{[5-({4-[(dimethylamino)sulfonyl]piperazinyl}methyl)-2-fluorophenyl]methyl}[(6-methyl(3-pyridyl))amino]carboxamide;

methyl 4-{[2-fluoro-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}methyl)phenyl]-methyl}piperazinecarboxylate;

N-[(3-{[4-(ethylsulfonyl)piperazinyl]methyl}-5-fluorophenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

methyl 4-{[2-chloro-5-({[(6-methyl(3-pyridyl))amino]carbonylamino}methyl)phenyl]-methyl}piperazinecarboxylate;

N-[(4-chloro-3-{[4-(ethylsulfonyl)piperazinyl]methyl}phenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-{[3-({4-[(dimethylamino)sulfonyl]piperazinyl}methyl)-4-chlorophenyl]methyl}[(6-methyl(3-pyridyl))amino]carboxamide;

N-[(3-{[4-(N,N-dimethylcarbamoyl)piperazinyl]methyl}-4-chlorophenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-({3-[(4-acetylpiperazinyl)methyl]-4-chlorophenyl}methyl)[(6-methyl(3-pyridyl))amino]carboxamide;

N-({4-chloro-3-[(4-cyanopiperazinyl)methyl]phenyl}methyl)[(6-methyl(3-pyridyl))amino]carboxamide;

methyl 4-{[2-fluoro-5-({[(6-methyl(3-pyridyl))amino]carbonylamino}methyl)phenyl]-methyl}piperazinecarboxylate;

N-({3-[(4-acetylpiperazinyl)methyl]-4-fluorophenyl}methyl)[(6-methyl(3-pyridyl))amino]carboxamide;

N-[(3-{[4-(ethylsulfonyl)piperazinyl]methyl}-4-fluorophenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-[(3-{[4-(N,N-dimethylcarbamoyl)piperazinyl]methyl}-4-fluorophenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-{[3-({4-[(dimethylamino)sulfonyl]piperazinyl}methyl)-4-fluorophenyl]methyl}[(6-methyl(3-pyridyl))amino]carboxamide;

N-{[3-({4-[(dimethylamino)sulfonyl]piperazinyl}methyl)-5-chlorophenyl]methyl}[(6-methyl(3-pyridyl))amino]carboxamide;

N-({5-chloro-3-[(4-cyanopiperazinyl)methyl]phenyl}methyl)[(6-methyl(3-pyridyl))amino]carboxamide;

N-[(3-{[4-(ethylsulfonyl)piperazinyl]methyl}-5-methylphenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-({3-[(4-acetylpiperazinyl)methyl]-5-methylphenyl}methyl)[(6-methyl(3-pyridyl))amino]carboxamide;

N-{[3-({4-[(dimethylamino)sulfonyl]piperazinyl}methyl)-5-methylphenyl]methyl}[(6-methyl(3-pyridyl))amino]carboxamide;

N-[(3-{[4-(ethylsulfonyl)piperazinyl]methyl}-4-methylphenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-{[3-({4-[(dimethylamino)sulfonyl]piperazinyl}methyl)-4-methylphenyl]methyl}[(6-methyl(3-pyridyl))amino]carboxamide;

N-({3-[(4-acetylpiperazinyl)methyl]-4-methylphenyl}methyl)[(6-methyl(3-pyridyl))amino]carboxamide;

methyl 4-{[4-(difluoromethoxy)-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}-methyl)phenyl]methyl}piperazinecarboxylate;

ethyl 4-{[4-(difluoromethoxy)-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}-methyl)phenyl]methyl}piperazinecarboxylate;

ethyl 4-{[3-({[(6-cyano(3-pyridyl))amino]carbonylamino}methyl)-4-fluorophenyl]methyl}piperazinecarboxylate;

methyl 4-{[2-methyl-5-({[(6-methyl(3-pyridyl))amino]carbonylamino}methyl)phenyl]-methyl}piperazinecarboxylate;

ethyl 4-{[4-fluoro-3-({[(6-methoxy(3-pyridyl))amino]carbonylamino}methyl)phenyl]-methyl}piperazinecarboxylate;

ethyl 4-[(4-fluoro-3-{[(pyrimidin-5-ylamino)carbonylamino]methyl}phenyl)methyl]-piperazinecarboxylate;

N-[(2-fluoro-5-{[4-(methylsulfonyl)piperazinyl]methyl}phenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

methylethyl 4-{[4-fluoro-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}methyl)-phenyl]methyl}piperazinecarboxylate;

N-{[2-fluoro-5-({4-[(methylethyl)sulfonyl]piperazinyl}methyl)phenyl]methyl}[(6-methyl(3-pyridyl))amino]carboxamide;

N-[(2-fluoro-5-{[4-(3-methylbutanoyl)piperazinyl]methyl}phenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-[(2-fluoro-5-{[4-(propylsulfonyl)piperazinyl]methyl}phenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-[(5-{[4-(2,2-dimethyl propanoyl)piperazinyl]methyl}-2-fluorophenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

ethyl 4-{[2-(difluoromethoxy)-5-({[(6-methyl(3-pyridyl))amino]carbonylamino}-methyl)phenyl]methyl}piperazinecarboxylate;

N-[(4-(difluoromethoxy)-3-{[4-(ethylsulfonyl)piperazinyl]methyl}phenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-[(4-(difluoromethoxy)-3-{[4-(methylsulfonyl)piperazinyl]methyl}phenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

ethyl 4-{[4-fluoro-3-({[(3-methylisoxazol-5-yl)amino]carbonylamino}methyl)phenyl]-methyl}piperazinecarboxylate;

ethyl 4-{[3-({[(6-acetyl(3-pyridyl))amino]carbonylamino}methyl)-4-fluorophenyl]methyl}piperazinecarboxylate;

methyl 4-{[4-methyl-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}methyl)phenyl]-methyl}piperazinecarboxylate;

ethyl 4-{[4-methyl-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}methyl)phenyl]-methyl}piperazinecarboxylate;

methylethyl 4-{[4-methyl-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}methyl) -phenyl]methyl}piperazinecarboxylate;

N-[(5-{[4-(ethylsulfonyl)piperazinyl]methyl}-2-methylphenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-({5-[(4-acetylpiperazinyl)methyl]-2-methylphenyl}methyl)[(6-methyl(3-pyridyl))amino]carboxamide;

[(6-methyl(3-pyridyl))amino]-N-[(2-methyl-5-{[4-(methylsulfonyl)piperazinyl]-methyl}phenyl)methyl]carboxamide;

[(6-methyl(3-pyridyl))amino]-N-{[2-methyl-5-({4-[(methylethyl)sulfonyl]piperazinyl}-methyl)phenyl]methyl}carboxamide;

[(6-methyl(3-pyridyl))amino]-N-[(2-methyl-5-{[4-(2-methylpropanoyl)piperazinyl]-methyl}phenyl)methyl]carboxamide;

tert-butyl 4-{[2,4-difluoro-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}-methyl)phenyl]methyl}piperazinecarboxylate;

methyl 4-{[2,4-difluoro-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}-methyl)phenyl]methyl}piperazinecarboxylate;

ethyl 4-{[2,4-difluoro-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}-methyl)phenyl]methyl}piperazinecarboxylate;

N-({3-[(4-acetylpiperazinyl)methyl]-2,6-difluorophenyl}methyl)[(6-methyl(3-pyridyl))amino]carboxamide;

N-[(2,6-difluoro-3-{[4-(methylsulfonyl)piperazinyl]methyl}phenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-[(3-{[4-(ethylsulfonyl)piperazinyl]methyl}-2,6-difluorophenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-{[3-({4-[(dimethylamino)sulfonyl]piperazinyl}methyl)-2,6-difluorophenyl]methyl}[(6-methyl(3-pyridyl))amino]carboxamide;

[(6-cyano(3-pyridyl))amino]-N-[(5-{[4-(ethylsulfonyl)piperazinyl]methyl}-2-fluorophenyl)methyl]carboxamide;

[(6-acetyl(3-pyridyl))amino]-N-[(5-{[4-(ethylsulfonyl)piperazinyl]methyl}-2-fluorophenyl)methyl]carboxamide;

ethyl 4-{[4-fluoro-3-({[(2-methylpyrimidin-5-yl)amino]carbonylamino}methyl)phenyl]-methyl}piperazinecarboxylate;

N-[(5-{[4-(ethylsulfonyl)piperazinyl]methyl}-2-fluorophenyl)methyl][(6-methoxy(3-pyridyl))amino]carboxamide;

N-[(5-{[4-(ethylsulfonyl)piperazinyl]methyl}-2-fluorophenyl)methyl](pyrimidin-5-ylamino)carboxamide;

tert-butyl 4-{[4-chloro-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}methyl)phenyl]-methyl}piperazinecarboxylate;

N-[(5-{[4-(ethylsulfonyl)piperazinyl]methyl}-2-fluorophenyl)methyl][(2-methylpyrimidin-5-yl)amino]carboxamide;

N-{[2-chloro-5-(piperazinylmethyl)phenyl]methyl}[(6-methyl(3-pyridyl))amino]carboxamide;

methyl 4-{[4-chloro-3-({[(6-methyl(3-pyridyl))amino]carbonylamino}methyl) -phenyl]methyl}piperazinecarboxylate;

N-[(2-chloro-5-{[4-(methylsulfonyl)piperazinyl]methyl}phenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-[(2-chloro-5-{[4-(ethylsulfonyl)piperazinyl]methyl}phenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide;

N-{[4-({4-[(dimethylamino)sulfonyl]piperazinyl}methyl)phenyl]methyl}[(6-methyl(3-pyridyl))amino]carboxamide;

N-[(5-{[4-(ethylsulfonyl)piperazinyl]methyl}-2-fluorophenyl)methyl][(6-methoxy(3-pyridyl))amino]carboxamide; and

N-[(5-{[4-(ethylsulfonyl)piperazinyl]methyl}-2-fluorophenyl)methyl][(6-methyl(3-pyridyl))amino]carboxamide,

or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition of claim 2 , wherein the composition is formulated in a form chosen from injectable fluids, aerosols, tablets, pills, capsules, syrups, creams, gels, and transdermal patches.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 27, 2007
From: MORGAN, BRADLEY P.; MUCI, ALEX; KRAYNACK, ERICA A.; TOCHIMOTO, TODD; LU, PU-PING; MORGANS, DAVID J., JR.
To: CYTOKINETICS, INC.
Reel/Frame 019221/0783 →
Continuity (2)
Provisional Application 6075098600 · Dec 15, 2005
Related Publication 20070197504A1 · Aug 23, 2007