US 12,404,260 B2
Pyridine rings containing derivatives as MALT1 inhibitors
Johannes Wilhelmus J. Thuring, Antwerp (BE); Tianbao Lu, Churchville, PA (US); Tongfei Wu, Boortmeerbeek (BE); Gaston Stanislas M. Diels, Turnhout (BE); Didier Jean-Claude Berthelot, La Neuville Chant d'Oisel (FR); and Berthold Wroblowski, Vosselaar (BE)
Assigned to Janssen Pharmaceutica NV, Beerse (BE)
Appl. No. 17/602,885
Filed by Janssen Pharmaceutica NV, Beerse (BE)
PCT Filed Apr. 10, 2020, PCT No. PCT/EP2020/060307
§ 371(c)(1), (2) Date Oct. 11, 2021,
PCT Pub. No. WO2020/208222, PCT Pub. Date Oct. 15, 2020.
Claims priority of provisional application 62/832,608, filed on Apr. 11, 2019.
Claims priority of application No. 19178959 (EP), filed on Jun. 7, 2019.
Prior Publication US 2022/0162187 A1, May 26, 2022
Int. Cl. C07D 401/14 (2006.01); C07D 401/12 (2006.01); C07D 405/14 (2006.01)
CPC C07D 401/14 (2013.01) [C07D 401/12 (2013.01); C07D 405/14 (2013.01)] 9 Claims
 
1. A compound of Formula (I)

OG Complex Work Unit Chemistry
wherein
Rx represents hydrogen, C1-4alkyl, or C3-6cycloalkyl;
Ry represents hydrogen, C1-4alkyl, or C3-6cycloalkyl; and
Rz represents hydrogen;
or
Rx and Ry are taken together to form a bivalent radical —Rx—Ry— wherein —Rx—Ry— represents —(CH2)n— or —CH2—O—(CH2)2—; wherein n represents 2, 3, 4 or 5; and
Rz represents hydrogen;
or
Ry represents hydrogen, C1-4alkyl, or C3-6cycloalkyl;
Rx and Rz are taken together to form together with the carbon atom to which they are attached a C3-6cycloalkyl;
R1 is selected from the group consisting of hydrogen, —OR5, C1-4alkyl, C2-4alkenyl, halo, —CN, C3-6cycloalkyl, Heta, —C(═O)—OH, —C(═O)—O—C1-4alkyl, —NR6aR7a and —C(═O)—NR6bR7b;
R2a and R2b are each independently selected from the group consisting of hydrogen, —O—C1-4alkyl, halo, —NR6cR7c, C3-6cycloalkyl, C1-4alkyl, and C1-4alkyl substituted with 1, 2 or 3 halo atoms;
X1 represents N or CRa;
X2 represents N or CRb;
such that only one of X1 and X2 are N in any instance;
R3 represents hydrogen, C1-4alkyl or —O—C1-4alkyl;
R4 represents halo, cyano or trifluoromethyl;
R5 is selected from the group consisting of hydrogen, C1-4alkyl, C3-6cycloalkyl, Hetb, and C1-4alkyl substituted with one or two substituents each independently selected from the group consisting of —OH, halo, —C(═O)—NR8R9, —C(═O)—OH, —C(═O)—O—C1-4alkyl, C3-6cycloalkyl and phenyl;
R6a, R6b, R6c, R7a, R7b, R7c, R8 and R9 each independently are selected from the group consisting of hydrogen and C1-4alkyl;
Heta represents a monocyclic 4- to 7-membered non-aromatic heterocyclyl containing one or two heteroatoms selected from nitrogen, oxygen and sulfur;
Hetb represents a monocyclic 4- to 7-membered non-aromatic heterocyclyl containing one or two heteroatoms selected from nitrogen, oxygen and sulfur;
Ra represents C1-4alkyl or —O—C1-4alkyl, each optionally substituted with one, two or three halo substituents;
or
Ra represents 2H-1,2,3-triazol-2-yl or C3-6cycloalkyl; each optionally substituted on one or two carbon atoms with a substituent each independently selected from the group consisting of C1-4alkyl, and C1-4alkyl substituted with one —OH;
Rb represents hydrogen;
or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.