US 7,550,487 B2
Pyrrolidine-3,4-dicarboxamide derivatives
Lilli Anselm, Binzen (Germany); Katrin Groebke Zbinden, Basel (Switzerland); Wolfgang Haap, Loerrach (Germany); Jacques Himber, Guebwiller (France); Christoph Martin Stahl, Freiburg (Germany); and Stefan Thomi, Basel (Switzerland)
Assigned to Hoffmann-La Roche Inc., Nutley, N.J. (US)
Filed on Mar. 09, 2005, as Appl. No. 11/76,162.
Claims priority of application No. 04101265 (EP), filed on Mar. 26, 2004.
Prior Publication US 2005/0215599 A1, Sep. 29, 2005
Int. Cl. A61K 31/443 (2006.01); A61K 31/401 (2006.01); C07D 43/02 (2006.01)
U.S. Cl. 514—343  [514/422; 514/423; 546/278.1; 548/517; 548/530] 30 Claims
 
1. A compound of the formula:

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof, wherein:
X is C—R6;
R1 is selected from the group consisting of: (1) hydrogen, (2) C1-7 alkyl, (3) C3-10 cycloalkyl, (4) C3-10 cycloalkyl-C1-7 alkyl, (5) fluoro-C1-7 alkyl, (6) hydroxy-C1-7 alkyl, (7) CN—C1-7 alkyl, (8) hydroxy substituted fluoro-C1-7 alkyl, (9) C2-7 alkinyl, (10) R10C(O)—, (11) R10OC(O)—, (12) N(R11,R12)C(O)—, (13) R10OC(O)—C1-7 alkyl, (14) N(R11,R12)C(O)—C1-7 alkyl, (15) R10—SO2, (16) R10—SO2—C1-7 alkyl, (17) N(R11,R12)—SO2, (18) N(R11,R12)—SO2—C1-7 alkyl, (19) aryl-C1-7 alkyl, (20) heteroaryl, (21) heteroaryl-C1-7 alkyl, (22) C1-7 alkoxy-C1-7 alkyl, (23) C1-7 alkoxycarbonyl-C3-10 cycloalkyl-C1-7 alkyl, and (24) heterocyclyl-C1-7 alkyl;
R2 is hydrogen or C1-7 alkyl;
R3 is aryl, aryl-C1-7 alkyl, heteroaryl or heteroaryl-C1-7 alkyl;
R4 is hydrogen, C 1-7 alkyl or hydroxy;
R5, R6, R7 and R8 independently from each other are selected from the group consisting: of (1) hydrogen, (2) halogen, (3) C1-7 alkyl, (4) C1-7 alkoxy, (5) fluoro-C1-7 alkyl, (6) fluoro-C1-7 alkyloxy, and (7) CN;
R9 is aryl, heterocyclyl, heteroaryl or heterocyclyl-C(O)—;
R10 is selected from the group consisting of: (1) hydrogen, (2) C1-7 alkyl, (3) C3-10 cycloalkyl, (4) C3-10 cycloalkyl-C1-7 alkyl, (5) hydroxy-C1-7 alkyl, (6) fluoro-C1-7 alkyl, (7) C1-7 alkyl-SO2—C1-7 alkyl, (8) aryl, (9) aryl-C1-7 alkyl, (10) heteroaryl, (11) heteroaryl-C1-7 alkyl, and (12) heterocyclyl;
R11 and R12 independently from each other are selected from the group consisting of: (1) hydrogen, (2) C1-7 alkyl, (3) hydroxy-C1-7 alkyl, (4) fluoro-C1-7 alkyl, (5) C3-10 cycloalkyl, (6) C3-10 cycloalkyl-C1-7 alkyl, (7) aryl, (8) aryl-C1-7 alkyl, (9) heteroaryl, and (10) heteroaryl-C1-7 alkyl; or R11 and R12, together with the nitrogen atom to which they are attached, form a heterocyclic ring selected from the group consisting of: (1) piperidinyl, (2) piperazinyl, (3) morpholinyl, (4) pyrrolidinyl, (5) pyrrolinyl and (6) azetidinyl, which said heterocyclic ring can optionally be substituted with C1-7 alkyl, halogen or hydroxy.