US 12,077,521 B2
Pyrazole derivatives as MALT1 inhibitors
Tianbao Lu, Churchville, PA (US); Brett Douglas Allison, San Diego, CA (US); Joseph Kent Barbay, Flourtown, PA (US); Peter J. Connolly, New Providence, NJ (US); Maxwell David Cummings, Ambler, PA (US); Gaston Diels, Beerse (BE); James Patrick Edwards, Ambler, PA (US); Kevin D. Kreutter, Plainsboro, NJ (US); Ulrike Philippar, Antwerp (BE); Fang Shen, Fort Washington, NJ (US); Johannes Wilhelmus John Fitzgerald Thuring, Antwerp (BE); Tongfei Wu, Hever (BE); and Didier Jean-Claude Berthelot, La Neuville Chant d'Oisel (FR)
Assigned to Janssen Pharmaceutica NV, Beerse (BE)
Filed by Janssen Pharmaceutica NV, Beerse (BE)
Filed on Nov. 25, 2020, as Appl. No. 17/104,081.
Application 17/104,081 is a division of application No. 15/847,999, filed on Dec. 20, 2017, granted, now 10,954,214.
Claims priority of provisional application 62/437,384, filed on Dec. 21, 2016.
Prior Publication US 2022/0315557 A1, Oct. 6, 2022
Int. Cl. C07D 401/14 (2006.01); A61P 1/00 (2006.01); A61P 11/06 (2006.01); A61P 19/02 (2006.01); A61P 35/00 (2006.01); A61P 37/00 (2006.01); C07D 401/12 (2006.01); C07D 405/14 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01); C07D 491/04 (2006.01); C07D 495/04 (2006.01)
CPC C07D 401/14 (2013.01) [A61P 1/00 (2018.01); A61P 11/06 (2018.01); A61P 19/02 (2018.01); A61P 35/00 (2018.01); A61P 37/00 (2018.01); C07D 401/12 (2013.01); C07D 405/14 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01); C07D 491/04 (2013.01); C07D 495/04 (2013.01)] 18 Claims
 
1. A method of treating a disease associated with MALT1 activity in a subject comprising administering to the subject in need thereof a therapeutically effective amount of a composition comprising a compound of Formula (I)

OG Complex Work Unit Chemistry
wherein
R1 is 1-oxo-1,2-dihydroisoquinolin-5-yl or 1-hydroxyisoquinolin-5-yl;
R2 is selected from the group consisting of C1-4alkyl, 1-methoxy-ethyl, difluoromethyl, fluoro, chloro, bromo, cyano, and trifluoromethyl;
G1 is N or C(R4);
G2 is N or C(R3); such that only one of G1 and G2 are N in any instance;
R3 is independently selected from the group consisting of trifluoromethyl, cyano, C1-4alkyl, fluoro, chloro, bromo, methylcarbonyl, methylthio, methylsulfinyl, and methanesulfonyl; or, when G1 is N, R3 is further selected from C1-4alkoxycarbonyl;
R4 is selected from the group consisting of
(i) hydrogen, when G2 is N;
(ii) C1-4alkoxy;
(iii) cyano;
(iv) cyclopropyloxy;
(v) (4-aminobutyl)aminocarbonyl;
(vi) (4-amino)butoxy;
(vii) methoxycarbonyl;
(viii) (E)-(4-aminobut-1-en-1-yl-aminocarbonyl; and
(ix) difluoromethoxy;
R5 is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, methoxy, methylsulfonyl, cyano, C1-4alkyl, ethynyl, trifluoromethyl, hydroxyethyl, methylcarbonyl, methylsulfinyl, methylthio, and 1,1-difluoroethyl;
R6 is hydrogen, C1-4alkyl, fluoro, 2-methoxy-ethoxy, chloro, cyano, or trifluoromethyl; and
R7 is hydrogen or fluoro;
or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.