US 7,320,992 B2
Substituted 2,3-dihydro-1h-isoindol-1-one derivatives and methods of use
Christopher Tegley, Thousand Oaks, Calif. (US); Jeffrey A. Adams, Thousand Oaks, Calif. (US); Benny C. Askew, Jr., Newbury Park, Calif. (US); Michael Croghan, Thousand Oaks, Calif. (US); Daniel Elbaum, Newton, Mass. (US); Julie Germain, Medford, Mass. (US); Gregory J. Habgood, Merrimac, Mass. (US); Scott Harried, Woodland Hills, Calif. (US); Aiwen Li, Westlake Village, Calif. (US); Nobuko Nishimura, West Hills, Calif. (US); Rana Nomak, Istanbul (Turkey); Andrew Tasker, Simi Valley, Calif. (US); and Kevin Yang, San Gabriel, Calif. (US)
Assigned to Amgen Inc., Thousand Oaks, Calif. (US)
Filed on Aug. 24, 2004, as Appl. No. 10/926,238.
Claims priority of provisional application 60/497878, filed on Aug. 25, 2003.
Prior Publication US 2005/0054670 A1, Mar. 10, 2005
Int. Cl. A61K 31/4439 (2006.01); C07D 401/12 (2006.01)
U.S. Cl. 514—339  [546/277.1; 546/152; 546/139; 546/113; 548/472; 544/111; 514/416; 514/314; 514/307; 514/300; 514/231.5] 38 Claims
 
1. A compound of Formula I

OG Complex Work Unit Drawing
wherein X is CH;
wherein Y is selected from C1-3-alkyl, C2-3-alkenyl,and NR4;
wherein Z is CHR5;
wherein R is selected from
a) substituted or unsubstituted 6-10 membered aryl,
b) substituted or unsubstituted 4-6 membered heterocyclyl,
c) substituted or unsubstituted 9-14 membered fused heterocyclyl,
d) substituted or unsubstituted aryl-C1-2-alkyl, and
e) substituted or unsubstituted heterocyclyl-C1-2-alkyl;
where substituted R is substituted with one or more substituents selected from halo, —OR3, —SR3, —SO2R3, —CO2R3, —C(O)NR3R3, —C(O)R3, —NR3R3, —SO2NR3R3, —NR3C(O)OR3, —NR3C(O)R3, optionally substituted 3-6 membered heterocyclyl, optionally substituted phenyl, alkylaminoalkoxyalkoxy, nitro, cyano, oxo, lower alkyl substituted with one or more R2;
wherein R1 is selected from unsubstituted or substituted
a) 6-10 membered aryl,
b) 5-6 membered heterocyclyl,
c) 9-14 membered fused heterocyclyl,
d) cycloalkyl,
e) cycloalkenyl,
f) lower alkyl, and
g) lower alkenyl,
wherein substituted R1 is substituted with one or more substituents independently selected from halo, —OR3, —SR2, —CO2R3, —C(O)NR3R3, —C(O)R3, —NR3R3, oxo, —OC(O)R3, —SO2R3, —SO2NR3R3, —NR3C(O)OR3, —NR3C(O)R3, —NR3C(O)NR3R3, optionally substituted cycloalkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted phenyl, cyano, aminoalkylcarbonylamino, alkylaminoalkylcarbonylamino, alkylaminoalkoxy, alkylaminoalkoxyalkoxy, nitro, and lower alkyl substituted with one or more R2;
wherein R2 is selected from H, halo, —OR3, amino, C1-2-alkylamino, C1-3-dialkylamino, C1-3-alkyl, optionally substituted phenyl, optionally substituted phenyl-C1-3-alkyl, 4-6 membered heterocyclyl, and optionally substituted 4-6 membered heterocyclyl-C1-C3-alkyl;
wherein R3 is independently selected from H, lower alkyl, optionally substituted phenyl, optionally substituted 3-6 membered heterocyclyl, optionally substituted C3-C6-cycloalkyl, optionally substituted phenylalkyl, optionally substituted 3-6 membered heterocyclylalkyl, optionally substituted C3-C6 cycloalkylalkyl and lower haloalkyl;
wherein R4 is independently selected from H, and lower alkyl;
wherein R5 is H; and
wherein R6 is selected from H, halo, —OR2, —SR3, —CO2R3, —SOR3, —C(O)NR3R3, —C(O)R3, —NR3R, —SO2R3, —SO2,NR3R3, —3NR3C(O)OR3, —NR3C(O)R3, —NR3C(O)NR3R3, optionally substituted cycloalkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted phenyl, cyano, nitro, lower alkyl substituted with one or more R2, lower alkenyl substituted with one or more R2 and lower alkynyl substituted with one or more R2;
and pharmaceutically acceptable salts thereof.