US 12,410,179 B2
Modulators of TNF alpha activity and uses thereof
Pengyu Yang, San Diego, CA (US); Lynnie Trzoss, San Diego, CA (US); Venkat Bollu, San Diego, CA (US); Junhu Zhang, San Diego, CA (US); and Qing Dong, San Diego, CA (US)
Assigned to RAYTHERA, INC., San Diego, CA (US)
Filed by RayThera, Inc., San Diego, CA (US)
Filed on Aug. 22, 2024, as Appl. No. 18/812,527.
Application 18/812,527 is a continuation of application No. PCT/US2024/042661, filed on Aug. 16, 2024.
Claims priority of provisional application 63/650,626, filed on May 22, 2024.
Claims priority of provisional application 63/613,206, filed on Dec. 21, 2023.
Claims priority of provisional application 63/519,990, filed on Aug. 16, 2023.
Prior Publication US 2025/0066375 A1, Feb. 27, 2025
Int. Cl. C07D 487/22 (2006.01); A61K 31/55 (2006.01); A61K 31/675 (2006.01); C07D 471/22 (2006.01); C07F 9/6561 (2006.01)
CPC C07D 487/22 (2013.01) [A61K 31/55 (2013.01); A61K 31/675 (2013.01); C07D 471/22 (2013.01); C07F 9/6561 (2013.01)] 16 Claims
 
1. A compound of Formula (I*), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:

OG Complex Work Unit Chemistry
wherein:
Ring B is phenyl;
each R1 is independently halogen, —CN, —OH, —ORa, —NRcRd, C1-C6alkyl, or C1-C6haloalkyl;
n is 0, 1, or 2;
R2 is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or cycloalkyl;
X is CRX;
RX is hydrogen;
Y is CRY;
RY is hydrogen, halogen, or C1-C6alkyl;
Z is CRZ;
RZ is hydrogen;
Ring A is heteroaryl;
each R3 is independently halogen, -L-CN, -L-NO2, -L-OH, -L-ORa, -L-OC(═O)Ra, -L-OC(═O)ORb, -L-OC(═O) NRcRd, -L-SH, -L-SRa, -L-S(═O)Ra, -L-S(═O)2Ra, -L-S(═O)(═NH) Ra, -L-S(═O)2ORb, -L-S(═O)2NRcRd, -L-NRcRd, -L-NRbC(═O)NRcRd, -L-NRbC(═O)Ra, -L-NRbC(═O)ORb, -L-NRbS(═O)2Ra, -L-C(═O)Ra, -L-C(═O)ORb, -L-C(═O)NRcRd, -L-P (═O)RcRd, -L-P (═O)ORcORd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;
or two R3 on adjacent atoms are taken together to form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each independently optionally substituted with one or more R;
m is 0, 1, or 2;
each Ra is independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;
each Rb is independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;
each Rc and Rd are independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;
or Rc and Rd are taken together with the atom to which they are attached to form a heterocycloalkyl independently optionally substituted with one or more R; and
L is absent or C1-C3alkylene optionally substituted with one or more R;
each R is independently halogen, —CN, —OH, —OC1-C3alkyl, —S(═O) C1-C3alkyl, —S(═O)2C1-C3alkyl, —S(═O)2NH2, —S(═O)2NHC1-C3alkyl, —S(═O)2N(C1-C3alkyl)2, —NH2, —NHC1-C3alkyl, —N(C1-C3alkyl)2, —NHC(═O)OC1-C3alkyl, —C(═O)C1-C3alkyl, —C(═O)OH, —C(═O)OC1-C3alkyl, —C(═O)NH2, —C(═O)N(C1-C3alkyl)2, —C(═O)NHC1-C3alkyl, —P(═O)(C1-C3alkyl)2, —P(═O)(OC1-C3alkyl)2, C1-C3alkyl, C1-C3haloalkyl, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C1-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl;
or two R on the same atom are taken together to form an oxo.