US 9,808,451 B2
Antiproliferative compounds and methods of use thereof
Brian E. Cathers, San Diego, CA (US); Matthew Daniel Correa, San Diego, CA (US); Joshua Hansen, La Jolla, CA (US); Antonia Lopez-Girona, San Diego, CA (US); Ehab M. Khalil, Whitehouse Station, NJ (US); Kyle MacBeth, San Francisco, CA (US); Hon-Wah Man, Princeton, NJ (US); George W. Muller, Rancho Santa Fe, CA (US); Michael Pourdehnad, San Francisco, CA (US); and Raj Raheja, Poway, CA (US)
Assigned to Celgene Corporation, Summit, NJ (US)
Filed by Celgene Corporation, Summit, NJ (US)
Filed on Sep. 23, 2016, as Appl. No. 15/275,045.
Application 15/275,045 is a continuation of application No. 14/795,837, filed on Jul. 9, 2015, granted, now 9,499,514.
Claims priority of provisional application 62/023,775, filed on Jul. 11, 2014.
Prior Publication US 2017/0007590 A1, Jan. 12, 2017
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/454 (2006.01); A61K 31/496 (2006.01); C07D 401/04 (2006.01); C07D 401/14 (2006.01); A61K 31/4545 (2006.01); A61K 31/501 (2006.01); A61K 31/506 (2006.01); A61K 31/5377 (2006.01); A61K 45/06 (2006.01); C07D 209/34 (2006.01)
CPC A61K 31/454 (2013.01) [A61K 31/4545 (2013.01); A61K 31/496 (2013.01); A61K 31/501 (2013.01); A61K 31/506 (2013.01); A61K 31/5377 (2013.01); A61K 45/06 (2013.01); C07D 401/04 (2013.01); C07D 401/14 (2013.01); C07D 209/34 (2013.01)] 19 Claims
 
1. A pharmaceutical composition comprising a compound of Formula I:

OG Complex Work Unit Drawing
or an enantiomer or a mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, or hydrate, thereof, wherein:
R1 is optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl;
R2 and R3 are each halo;
where the substituents on R1, when present, are one to three groups Q, where each Q is independently alkyl, halo, haloalkyl, alkoxyalkyl, oxo, hydroxyl, alkoxy, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted heteroaryl, —R4OR5, —R4OR5—R4OR5, —R4N(R6)(R7), —R4SR5, —R4OR4N(R6)(R7), —R4OR4C(J)N(R6)(R7), —C(J)R9 or R4S(O)tR8;
each R4 is independently alkylene, alkenylene or a direct bond;
each R5 is independently hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl or heterocyclylalkyl, where alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl or heterocyclylalkyl groups in R5 are each independently optionally substituted with 1-3 Q1 groups, where each Q1 is independently alkyl, haloalkyl or halo;
R6 and R7 are selected as follows:
i) R6 and R7 are each independently hydrogen or alkyl; or
ii) R6 and R7 together with the nitrogen atom on which they are substituted form a 5 or 6-membered heterocyclyl or heteroaryl ring, optionally substituted with one or two halo, alkyl or haloalkyl;
R8 is alkyl, haloalkyl, or hydroxyalkyl;
R9 is alkyl or aryl;
J is O or S; and
t is 1 or 2.