Therapeutic compounds and methods of use

A compound of formula (I):

• or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein:
• X1 is N or C—R5, wherein each R5 is independently selected from the group consisting of H, cyano, halo, C(O)NH2, N(Re)(Rf), C3-10cycloalkyl, C1-6alkoxy, C6-20aryl, and C1-6alkyl, wherein the C1-6alkyl of R5 is optionally substituted with hydroxyl or N(Re)(Rf), or
• the R5 of X1 is taken together with R3, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C1-6alkyl;
• X2 is N or C—R5, wherein each R5 is independently selected from the group consisting of H, cyano, halo, C(O)NH2, N(Re)(Rf), C3-10cycloalkyl, C1-6alkoxy, C6-20aryl, and C1-6alkyl, wherein the C1-6alkyl of R5 is optionally substituted with hydroxyl or N(Re)(Rf);
• X3 is N or C—H;
• R1 is:
• (i) a 3-5 membered saturated heterocyclyl comprising at least one annular oxygen atom, wherein the 3-5 membered saturated heterocyclyl is optionally substituted with one or more C1-6alkyl, or
• (ii) N(Re)(Rf), or
• wherein Ra, Rb, and Rc are each independently selected from the group consisting of H, halo, cyano, hydroxyl, B(OH)2, C(O)—OH, C(O)—N(Re)(Rf), C(O)—C1-6alkoxy, C(O)—C1-6alkyl, C1-6alkyl, C3-10cycloalkyl, C6-20aryl, 3-10 membered heterocyclyl, C5-13spirocyclyl, and 5-20 membered heteroaryl, wherein the C1-6alkyl is further optionally substituted with hydroxyl, or
• wherein Rd is selected from the group consisting of H, halo, cyano, hydroxyl, B(OH)2, C(O)—OH, C(O)—N(Re)(Rf), C(O)—C1-6alkoxy, C(O)—C1-6alkyl, C1-6alkyl, C3-10cycloalkyl, C6-20 aryl, 3-10 membered heterocyclyl, C5-13spirocyclyl, and 5-20 membered heteroaryl, wherein the C1-6alkyl is further optionally substituted with hydroxyl;
• L is absent or is selected from the group consisting of —O—, *—CH2—O—**, *—O—CH2—**, —CH═CH—, and —C≡C—, wherein ** indicates the attachment point to the R2 moiety and * indicates the attachment point to the remainder of the molecule;
• R2 is C1-12alkyl, C3-10cycloalkyl, 3-10 membered heterocyclyl, C5-13spirocyclyl, C6-20aryl, or 5-20 membered heteroaryl,
• wherein the C1-12alkyl, C3-10cycloalkyl, 3-10 membered saturated heterocyclyl, C5-13spirocyclyl, C6-20 aryl, or 5-20 membered heteroaryl of R2 is independently optionally substituted with one or more substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(Re)(Rf), and O(Re),
• provided that, when R2 is C1-12alkyl, wherein the C1-12alkyl of R2 is independently optionally substituted with one or more substituents selected from the group consisting of cyano, halo, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, NO2, N(Re)(Rf), and O(Re), then L is —CH═CH— or —C≡C—;
• R3 is cyano, C1-6alkyl, C1-4alkoxy, or C2-4alkenyl, wherein the C2-4alkenyl is optionally substituted with N(Re)(Rf), or
• R3 is taken together with R5 of X1, and the atoms to which they are attached, to form a 5-membered heterocyclyl or a 5-membered heteroaryl, wherein the 5-membered heterocyclyl or 5-membered heteroaryl is optionally substituted with one or more C1-6alkyl, or
• R3 is taken together with the carbon atom of *—CH2—O—** of L, and the atoms to which they are attached, to form a C6aryl or a 6-membered heteroaryl;
• R4 is H or C1-6alkyl, wherein the C1-6alkyl is optionally substituted with hydroxyl;
• and
• Re and Rf are, independently of each other and independently at each occurrence, selected from the group consisting of H, cyano, hydroxyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C5-13spirocyclyl, C6-20aryl, and 3-20 membered heteroaryl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C1-6alkyl-C3-10cycloalkyl, 3-10 membered heterocyclyl, C5-13spirocyclyl, C6-20aryl, and 3-20 membered heteroaryl of Re and Rf are each independently optionally substituted with one or more substituents selected from the group consisting of C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, oxo, cyano, halo, NO2, and hydroxyl.