WDR5-MYC inhibitors

A compound of formula (I), or a pharmaceutically acceptable salt thereof,

• wherein
• Y is —XR5b, C(O)OH, or C(O)OC1-4alkyl;
• X is O, S, N, or NR5a,
• R0 is hydrogen or halogen;
• R1 is halogen, cyano, SF5, C1-6alkyl, C2-6alkenyl, C1-4haloalkyl, —OC1-4alkyl, —OC1-4haloalkyl, or R1G;
• R1G is C3-6cycloalkyl, C5-6cycloalkenyl, phenyl, a 4- to 6-membered heterocyclyl, or a 5- to 6-membered heteroaryl, wherein R1G is optionally substituted with 1-4 substituents independently selected from the group consisting of halogen, cyano, oxo or a cyclic ketal thereof, C1-4alkyl, and C1-4haloalkyl;
• R2 is hydrogen, C1-4alkyl, —OC1-4alkyl, —OC1-4haloalkyl, halogen, or OH;
• R3 is C(O)OR3a, C(O)NR3bR3c, C(O)R3a, SR3d, S(O)R3d, S(O)2R3d, S(O)2NR3bR3c, NO2, NR3bC(O)R3c, or NR3bC(O)NR3bR3c,
• R3a is hydrogen, C1-8alkyl, C1-8haloalkyl, -L1-R30, G1, or -L1-G2;
• R3b and R3c are independently hydrogen, C1-8alkyl, C1-8haloalkyl, -L1-R30, G1, or -L1-G2, wherein
• R3b and R3c together with the nitrogen to which they attach optionally form a 3- to 8-membered heterocyclyl, the heterocyclyl being optionally substituted with 1-4 substituents independently selected from the group consisting of halogen, cyano, C1-4alkyl, C1-4haloalkyl, oxo, OH, —OC1-4alkyl, —OC1-4haloalkyl, —C1-6alkylene-OH, —C1-6alkylene-OC1-4alkyl, NH2, —NHC1-4alkyl, —N(C1-4alkyl)2, and —S(O)2C1-4alkyl;
• or
• R3b and R3c together with the intervening —NC(O)— or —NC(O)N(R3b)—, optionally form a 5- to 8-membered heterocyclyl, the heterocyclyl being optionally substituted with 1-4 substituents independently selected from the group consisting of halogen, cyano, C1-4alkyl, C1-4haloalkyl, oxo, OH, —OC1-4alkyl, —OC1-4haloalkyl, NH2, —NHC1-4alkyl, and —N(C1-4alkyl)2;
• R3d is C1-8alkyl, C1-8haloalkyl, -L1-R30, G1, or -L1-G2;
• L1 is C1-6alkylene, wherein the C1-6alkylene is optionally substituted with halogen, OH, COOH, —C(O)OC1-4alkyl, C(O)NH2, —C(O)NHC1-4alkyl, or —C(O)N(C1-4alkyl)2;
• R30 is —OR30a, —SR30a, —NR30bR30c, COOH, —C(O)OC1-4alkyl, C(O)NH2, —C(O)NHC1-4alkyl, or —C(O)N(C1-4alkyl)2;
• R30a, R30b, and R30c are independently hydrogen, C1-4alkyl, C1-4haloalkyl, G1, or -L2 G2;
• L2 is C1-3alkylene;
• G1, at each occurrence, is independently C3-10carbocyclyl, a 6- to 12-membered aryl, a 5- to 12-membered heteroaryl, or a 4- to 12-membered heterocyclyl, wherein G1 is attached to the parent molecular moiety at a carbon atom of G1 and optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, cyano, C1-4alkyl, C1-4haloalkyl, oxo, OH, —OC1-4alkyl, —OC1-4haloalkyl, NH2, —NHC1-4alkyl, and —N(C1-4alkyl)2;
• G2, at each occurrence, is independently C3-10carbocyclyl, a 6- to 12-membered aryl, a 5- to 12-membered heteroaryl, or a 4- to 12-membered heterocyclyl, wherein G2 is optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, cyano, C1-4alkyl, C1-4haloalkyl, oxo, OH, —OC1-4alkyl, —OC1-4haloalkyl, NH2, —NHC1-4alkyl, and —N(C1-4alkyl)2;
• R4 is hydrogen, halogen, OH, —OC1-4alkyl, —OC1-4haloalkyl, —OC3-6cycloalkyl, NH2, —NHC1-4alkyl, —N(C1-4alkyl)2, —NHC3-6cycloalkyl, —N(C1-4alkyl) (C3-6cycloalkyl), or —N(C3-6cycloalkyl)2;
• R5a is hydrogen, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, or —C1-3alkylene-C3-6cycloalkyl;
• R5b is hydrogen, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, or —C1-3alkylene-C3-6cycloalkyl;
• alternatively, R5a and R5b, together with the nitrogen to which they attach form a 3- to 8-membered heterocyclyl, the heterocyclyl being optionally substituted with 1-4 substituents independently selected from the group consisting of halogen, cyano, C1-4alkyl, C1-4haloalkyl, OH, —OC1-4alkyl, —OC1-4haloalkyl, —C1-6alkylene-OH, and —C1-6alkylene-OC1-4alkyl;
• R6 is hydrogen, halogen, cyano, C(O)OH, SF5, NO2, C1-4alkyl, C1-4haloalkyl, —OC1-4alkyl, —OC1-4haloalkyl, —C1-6alkylene-OH, —C1-6alkylene-OC1-4alkyl, C3-6cycloalkyl, or a 4- to 7-membered heterocyclyl, wherein the cycloalkyl and heterocyclyl are optionally substituted with 1-4 substituents independently selected from the group consisting of halogen, cyano, C1-4alkyl, and C1-4haloalkyl;
• alternatively, R5b and R6, together with the intervening atoms form a 5- to 6-membered heteroaryl or a 5- to 7-membered heterocycle, wherein the heteroaryl and heterocycle are optionally substituted with 1-4 substituents independently selected from the group consisting of halogen, cyano, C1-4alkyl, and C1-4haloalkyl;
• R7 is hydrogen, halogen, cyano, C1-4alkyl, C1-4haloalkyl, —OC1-4alkyl, or —OC1-4haloalkyl;
• and
• R8 is halogen, cyano, C1-2alkyl, C1-2haloalkyl, —OC1-2alkyl, or —OC1-2haloalkyl;
• provided the compound of formula (I) is not
• 3-[[(6-methyl-8-quinolinyl)sulfonyl]amino]-5-(trifluoromethyl)-benzoic acid;
• 3-[[(5-bromo-2-methoxyphenyl)sulfonyl]amino]-5-(trifluoromethyl)-benzoic acid;
• or
• 3-[[(3-bromo-5-chloro-2-methoxyphenyl)sulfonyl]amino]-5-(trifluoromethyl)-benzoic acid.