Bi-heteroaryl compounds as vps34 inhibitors

A method for the treatment of cancer in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of a compound according to formula (I):

• or a pharmaceutically acceptable salt thereof, wherein
• R1 is C1-6alkyl, NR3R6, C1-6alkoxy, or —S—C1-6alkyl;
• R2 is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, a C6-14aryl group, a C3-14cycloalkyl group, a 5 to −14 membered heteroaryl containing 1 to 3 heteroatoms each independently selected from N, O, and S, C1-6alkoxy, C2-6-alkenyloxy, C2-6-alkynyloxy, C1-6alkyl-O—R27, C1-6alkyl-C3-14cycloalkyl, C1-6alkyl-O—C0-6alkyl-C6-14aryl, C1-6alkyl-O—SiR8R9R10, halogen, or C1-6haloalkyl, wherein R2 may be unsubstituted or substituted with OH, C1-6alkoxy, or halogen;
• R4 and R5 are independently H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, a C6-14aryl group, a C3-14cycloalkyl group, a 3-14 membered cycloheteroalkyl group, a 5-14 membered heteroaryl group, C1-6alkoxy, OH, C1-6alkylNR11R12, C1-6alkyl-O—R13, C1-6alkyl-5-14 membered heteroaryl group, or C(O)—C1-6alkyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C6-14aryl group, C3-14cycloalkyl group, 3-14 membered cycloheteroalkyl group, 5-14 membered heteroaryl group, C1-6alkoxy, C1-6alkyl-NR11R12, C1-6alkylOR13, C1-6alkyl-5-14 membered heteroaryl group, or C(O)—C1-6alkyl may be optionally substituted by one or more from the group of halogen, a 5-14 membered heteroaryl group, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkylOR27, C1-6alkoxy, NR14R15, CONR16R17, NR18COR19, NR20COOR21, COR22, COOR23, —CN, SO2R26, or NR24SO2R25;
• R3 and R6 are independently H, C1-6alkyl, C1-6alkyl-aryl, C1-6alkoxy, a C3-14cycloalkyl group, a 3-14 membered cycloheteroalkyl group, a C6-14aryl group, a 5-14 membered heteroaryl group, or C1-6alkyl-O—R8, wherein C1-6alkyl, C1-6alkyl-aryl, C1-6alkoxy, a C3-14cycloalkyl group, a 3-14 membered cycloheteroalkyl group, a C6-14aryl group, a 5-14 membered heteroaryl group, or C1-6alkyl-O—R8, may be substituted by one of more of C1-6alkyl, or OH;
• R11 and R12 are the same or different, and independently are selected from hydrogen, C1-6alkyl, a C3-8cycloalkyl group, a C6-14 aryl group, a 5-14 membered heteroaryl group, and a 3-14 membered cycloheteroalkyl group, or NR11R12 forms a non-aromatic four to seven membered ring optionally containing a second heteroatom selected from O, N and S, and optionally substituted by one or more substituents R28;
• R7 and R7a are independently H or C1-6alkyl
• n is 0, 1, or 2;
• and
• R8, R9, R10, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, and R27, and R28 are independently H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, a C6-14 aryl group, A C3-14 cycloalkyl group, a 3-14 membered cycloheteroalkyl group, or a 5-14 membered heteroaryl group.

A method for the treatment of cancer in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of a compound of Formula II,

• or a pharmaceutically acceptable salt thereof, wherein
• R1 is (C1-C6)alkyl, —OCH3, —NH2, —NH(C1-C6)alkyl, —NHCH2(phenyl), —NHCH2CH2OH, —NHCH2CH(OH)CH3, —NHCH(CH3)CH2OH, —NHCH2CH(CH3)2OH, —NHCH2CH2OCH3, —NH(C3-C6)cycloalkyl, phenethylamino-, tetrahydropyranylamino-, or —SCH3;
• R2 is (C1-C6)alkyl, —CF3, —CH2(cyclopropyl), —CH2OH, or —CH2OCH2(phenyl);
• R4 is H;
• and
• R5 is
• (i) —(CH2)n—R5a, where n is 0, 1 or 2 and R5a is pyridinyl, 6-methoxypyridin-3-yl, furanyl, imidazolyl, isoxazolyl, thiazolyl, thiadiazolyl, quinolinyl, 1H-indolyl, benzo[d][1,3]dioxolyl, morpholinyl, tetrahydropyranyl, or piperidinyl, where said chemical moiety is optionally substituted with a methyl or halo;
• or
• (ii) (C1-C6)alkyl, (C3-C6)cycloalkyl, or phenyl, wherein said (C1-C6)alkyl, said (C3-C6)cycloalkyl, and said phenyl are optionally substituted with one to two substituents each independently selected from F, Cl, —CH3, —CN, —OH, —OCH3, —NHC(O)—(C1-C4)alkyl, —NH2, —N(CH3)2i—NHSO2CH3, —C(O)CH3, —C(O)OH, or —SO2CH3.