US 7,465,746 B2
Fluorinated 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP
Paul J. Coleman, Wallingford, Pa. (US); Christopher D. Cox, Harleysville, Pa. (US); Robert M. Garbaccio, Lansdale, Pa. (US); and George D. Hartman, Lansdale, Pa. (US)
Assigned to Merck & Co., Inc., Rahway, N.J. (US)
Filed on Aug. 11, 2004, as Appl. No. 10/915,743.
Claims priority of provisional application 60/563580, filed on Apr. 19, 2004.
Claims priority of provisional application 60/495637, filed on Aug. 15, 2003.
Prior Publication US 2005/0043357 A1, Feb. 24, 2005
Int. Cl. A61K 31/4468 (2006.01)
U.S. Cl. 514—326  [546/187] 14 Claims
 
1. The compound of Formula II:

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein:
b is 0 or 1;
m is 0, 1, or 2;
n is 0, 1, 2 or 3;
r is 0 or 1;
s is 0 or 1;
t is 0 or 1;
R1 and R2 are independently selected from: H or (C1-C6)alkyl, optionally substituted with one, two or three substituents selected from R7;
R3 is selected from:
1) hydrogen; or
3) CH2—O—Rd,
R4 is independently selected from:
1) halo,
2) OH, and
3) ObC1-C6 perfluoroalkyl;
R5 is selected from:
1) hydrogen and
2) halo,
R7 is selected from:
1) (C═O)rOs(C1-C10)alkyl,
2) Or(C1-C3)perfluoroalkyl,
3) oxo,
4) OH,
5) halo,
6) CN,
7) (C2-C10)alkenyl,
8) (C2-C10)alkynyl,
13) C(O)Ra,
14) (C0-C6)alkylene-CO2Ra,
15) C(O)H,
16) (C0-C6)alkylene-CO2H,
17) C(O)N(Rb)2,
18) S(O)mRa,
19) S(O)2N(Rb)2; and
20) —OPO(OH)2;
said alkyl, alkenyl, alkynyl, and alkylene is optionally substituted with up to three substituents selected from Rb, OH, (C1-C6)alkoxy, halogen, CO2H, CN, O(C═O)C1-C6 alkyl, oxo, NO2 and N(Rb)2;
R10 is selected from: F and —CH2F;
R13 is selected from: H and CH2F, provided that if t is 1, R13 is H, and if t is 0, R13 is —CH2F;
Rox is absent or is oxo;
Ra is (C1-C6)alkyl;
Rb H or (C1-C6)alkyl;
Rd is selected from: H or (C1-C6)alkyl.