Back to results
US 7,608,739 B2Granted
Mitotic kinesin inhibitors
AssigneeMerck & Co., Inc.
InventorsRobert M. Garbaccio, Christy M. Olson, Edward S. Tasber, Maricel Torrent
Life of this patent
Estimating the term…
Abstract
The present invention relates to N-substituted benzylic aniline derivatives that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention also relates to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.
Claims6
The compound of the Formula III;
- wherein:
- R1 is selected from:
- H, F and OH;
- R3 is selected from:
- H, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl and (C1-C6)alkyl hydroxyl;
- R4 is selected from:
- H, oxo, OH, halo, CN, NH2, NO2, (C═O)aOb(C1-C10)alkyl, (C═O)aOb(C2-C10)alkenyl, (C═O)aOb(C2-C10)alkynyl, (C═O)aOb(C3-C6)cycloalkyl, (C═O)aOb(C0-C6)alkylene-aryl, (C═O)aOb(C0-C6)alkylene-heterocyclyl, (C═O)aOb(C0-C6)alkylene-N(Rb)2, C(O)H, (C0-C6)alkylene-CO2H, C(O)N(Rb)2, and S(O)2N(Rb)2;
- said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkylene and heterocyclyl is optionally substituted with up to three substituents selected from Rb;
- R5 is H or CH3;
- Ra is selected from:
- (C1-C6)alkyl, (C3-C6)cycloalkyl, aryl and heterocyclyl;
- said alkyl, cycloalkyl, aryl and heterocyclyl is optionally substituted with one or more substituents selected from OH,(C1-6)alkyl, (C1-C6)alkoxy, halogen, CO2H, CN, (O)C═O(C1-C6)alkyl, oxo and N(Rc)2;
- Rb is independently selected from:
- H, oxo, OH, halogen, CO2H, CN, (O)C═O(C1-C6)alkyl, N(Rc)2, (C1-C6)alkyl, aryl, heterocyclyl, (C3-C6)cycloalkyl, (C═O)O(C1-C6)alkyl, C═O(C1-C6)alkyl and S(O)2Ra;
- said alkyl, cycloalkyl, aryl or heterocylyl is optionally substituted with one or more substituents selected from OH, (C1-C6)alkyl, (C1-C6)alkoxy, halogen, CO2H, CN, (O)C═O(C1-C6)alkyl, oxo, N(Rc)2 and optionally substituted heterocyclyl, wherein said heterocyclyl is optionally substituted with (C1-C6)alkyl, oxo or NH2;
- Rc is independently selected from:
- H and (C1-C6)alkyl;
- a is 0 or 1;
- b is 0 or 1;
- p is 1 or 2;
- q is 0 or 1;
- or a pharmaceutically acceptable salt or stereoisomer thereof.
19 more elements
A compound which is selected from:
- 3-[{3-chloro-4-fluorophenyl)(2-hydroxy-1-methylethyl)amino]methyl}phenol;
- 2-[benzyl(3-chloro-4-fluorophenyl)amino]propan-1-ol;
- N-2-benzyl-N-2-(3-chloro-4-fluorophenyl)-N-1-[2(dimethylamino)ethyl]alaninamide;
- N-2-benzyl-N-2-(3-chloro-4-fluorophenyl)alaninamide;
- methyl N-benzyl-N-(3-chloro-4-fluorophenyl)alanylglycinate;
- N-2-benzyl-N-2-(3-chloro-4-fluorophenyl)-N-1-(isoxazol-4-ylmethyl)alaninamide;
- 3-[benzyl(3-chloro-4-fluorophenyl)amino]-2-methylbutan-2-ol;
- N-2-benzyl-N-2-(3-chloro-4-fluorophenyl)-N-1,N-1-dimethylpropane-1,2-diamine;
- N-benzyl-3-chloro-4-fluoro-N-[1-methyl-2-(4-methylpiperazin-1-yl)ethyl]aniline;
- 2-[(3-chloro-4-fluorophenyl)(1-phenylethyl)amino]propan-1-ol;
- N-2-(3-chloro-4-fluorophenyl)-N-2-(3-hydroxybenzyl)-N-1-(isoxazol)-4-ylmethyl)alaninamide;
- N-2-(3-chloro-4-fluorophenyl)-N-2-(3-hydroxybenzyl)alaninamide;
- N-2-(3-chloro-4-fluorophenyl)-N-1-[2-(dimethylamino)ethyl]-N-2-(3-hydroxybenzyl)alaninamide;
- Methyl 2-[benzyl(3-chloro-4-fluorophenyl)amino]butanoate;
- Methyl 2-[benzyl(3-chloro-4-fluorophenyl)amino]pent-4-enoate;
- 2-[benzyl(3-chloro-4-fluorophenyl)amino]pent-4-en-1-ol;
- N-benzyl-N-(3-chloro-4-fluorophenyl)glycine;
- 2-[benzyl(3-chloro-4-fluorophenyl)amino]pentan-1-ol;
- 2-[benzyl(3-chloro-4-fluorophenyl)amino]butan-1-ol;
- N-benzyl-3-chloro-N-[1-({3-[(dimethylamino)methyl]piperidin-1-yl}carbonyl)propyl]-4-fluoroaniline;
- 2-[benzyl(3-chloro-4-fluorophenyl)amino]-N-methyl-N-[2-(1-methyl-1H-pyrazol-4-yl)ethyl]butanamide;
- 2-[benzyl(3-chloro-4-fluorophenyl)amino]-3-methylbutan-1-ol;
- 2-[benzyl(3-chloro-4-fluorophenyl)amino]pentane-1,5-diol;
- 2-[benzyl(3-chloro-4-fluorophenyl)amino]-3-cyclopropylpropan-1-ol;
- and
- N-2-benzyl-N-2-(3-chloro-4-fluorophenyl)-N1-[2-dimethylamino)ethyl]-2-methylalaninamide;
- or a pharmaceutically acceptable salt or stereoisomer thereof.
24 more elements
Dependencies are inferred from the claim text.