US 11,884,649 B2
IRE1α inhibitors and uses thereof
Feroz R. Papa, San Francisco, CA (US); Bradley J. Backes, San Francisco, CA (US); and Dustin J. Maly, Seattle, WA (US)
Assigned to The Regents of the University of California, Oakland, CA (US); and University of Washington, Seattle, WA (US)
Filed by The Regents of the University of California, Oakland, CA (US); and University of Washington, Seattle, WA (US)
Filed on Nov. 12, 2021, as Appl. No. 17/525,778.
Claims priority of provisional application 63/113,558, filed on Nov. 13, 2020.
Prior Publication US 2022/0153723 A1, May 19, 2022
Int. Cl. C07D 401/14 (2006.01); C07D 401/04 (2006.01)
CPC C07D 401/14 (2013.01) [C07D 401/04 (2013.01)] 15 Claims
 
1. A compound having the formula:

OG Complex Work Unit Chemistry
wherein,
Ring B is cyclohexyl or 3-piperidinyl;
i) L1 is —SO2— and R1 is —CH2CF3, unsubstituted cyclopropyl, unsubstituted cyclobutyl, or

OG Complex Work Unit Chemistry
 or
ii) L1 is —NHCO— and R1 is unsubstituted cyclopropyl;
R2 is hydrogen, halogen, or substituted or unsubstituted C1-C4 alkyl;
R3 is hydrogen, halogen, or substituted or unsubstituted C1-C4 alkyl;
R4 is independently oxo, halogen, —CX43, —CHX42, —CH2X4, —OCX43, —OCH2X4, —OCHX42, —CN, —SOn4R4D, —SOv4NR4AR4B, —NR4CNR4AR4B, —ONR4AR4B, —NHC(O)NR4CNR4AR4B, —NHC(O)NR4AR4B, —N(O)m4, —NR4AR4B, —C(O)R4C, —C(O)—OR4C, —C(O)NR4AR4B, —OR4D, —NR4ASO2R4D, —NR4AC(O)R4C, —NR4AC(O)OR4C, —NR4AOR4C, —SF5, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; two R4 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R4A, R4B, R4C, and R4D are independently hydrogen, —CCl3, —CBr3, —CF3, —CI3, —CHCl2, —CHBr2, —CHF2, —CHI2, —CH2Cl, —CH2Br, —CH2F, —CH2I, —CN, —OH, —NH2, —COOH, —CONH2, —OCCl3, —OCF3, —OCBr3, —OCI3, —OCHCl2, —OCHBr2, —OCHI2, —OCHF2, —OCH2Cl, —OCH2Br, —OCH2I, —OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R4A and R4B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
X4 is independently —F, —Cl, —Br, or —I;
n4 is an integer from 0 to 4;
m4 and v4 are independently 1 or 2;
z4 is an integer from 0 to 5;
R5, R6, and R7 are independently halogen, —CCl3, —CBr3, —CF3, —CI3, —CHCl2, —CHBr2, —CHF2, —CHI2, —CH2Cl, —CH2Br, —CH2F, —CH2I, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, —NHC(O)NH2, —NHSO2H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCCl3, —OCF3, —OCBr3, —OCI3, —OCHCl2, —OCHBr2, —OCHI2, —OCHF2, —OCH2Cl, —OCH2Br, —OCH2I, —OCH2F, —SF5, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
z5 is an integer from 0 to 3;
z6 is an integer from 0 to 2; and
z7 is an integer from 0 to 4;
or a salt thereof;
wherein when Ring B is cyclohexyl, then R1 is not unsubstituted cyclobutyl.