Chromenopyridine derivatives as phosphatidylinositol phosphate kinase inhibitors

A compound of Formula (I):

• or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
• wherein:
• Ring A1 is 6-membered heteroaryl;
• Ring A2 is heteroaryl optionally substituted with one or more R8;
• W is —O—, —N(C1-6 alkyl)-, —N(C3-8 cycloalkyl)-, —N(aryl)-, or —N(heteroaryl)-;
• G is a bond, —O—, —NH—, or —N(C1-6 alkyl)-;
• R1 is —N(R5)C(O)R6, —C(O)N(R5)(R6), —S(O)2N(R5)(R6), —N(R5)S(O)2R6, or heteroaryl, wherein the heteroaryl is optionally substituted with one or more R7;
• R2 is H, halogen, —OH, —NH2, —NO2, —CN, —COOH, —C(O)NH2, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• R3 and R4 are each independently —H, halogen, C1-6 alkyl, C1-6 alkoxy, or C3-6 cycloalkyl, wherein the C1-6 alkyl, C1-6 alkoxy, or C3-6 cycloalkyl is optionally substituted with one or more halogen, —OH, or —NH2;
• or
• R3 and R4 when taken together with the atom to which they are attached form a C3-8 cycloalkyl or heterocyclyl;
• R5 and R6 are independently, at each occurrence, —H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, wherein the C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with one or more R7;
• or
• R5 and R6 when taken together with the atom to which they are each attached form a heterocycle optionally substituted with one or more R7;
• each R7 is independently —H, halogen, —OH, —NH2, —NO2, —CN, C1-6 alkyl, C1-6 alkoxy, C3-8 cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• each R8 is independently —N(R9)C(O)R10, —N(R9)C(O)OR10, —N(R9)C(O)N(R9)(R10), —N(R9)C(O)N(R9)(R11), —N(R9)S(O)2R10, —N(R9)S(O)2N(R9)(R10), —S(O)2R10, —N(R9)(R10), —OR10, —CF3, —CHF2, —R10, —N(R9)C(O)R11, —N(R9)(R11), or halogen;
• or
• two R8 with the atoms to which they are attached form a C4-8 cycloalkyl or heterocyclyl, wherein the heterocyclyl or C4-8 cycloalkyl is optionally substituted with one or more R12;
• each R9 and R10 is independently, at each occurrence, —H, C1-6 alkyl, C3-8 cycloalkyl, or heterocyclyl, wherein the C1-6 alkyl, C3-8 cycloalkyl, or heterocyclyl is optionally substituted with one or more R13;
• or
• R9 and R10 when taken together with the atom to which they are each attached form a heterocycle optionally substituted with one or more R14;
• each R11 is independently aryl, C3-8 cycloalkyl, heterocyclyl, or heteroaryl, wherein the aryl or heteroaryl group is optionally substituted with one or more R18 and the C3-8 cycloalkyl or heterocyclyl is optionally substituted with one or more R19;
• each R12 is independently C1-6 alkyl, C3-6 cycloalkyl, —OR20, —C(O)R20, —C(O)OR20, —S(O)2R20, or oxo;
• or
• two R12 taken together can form a C3-8 cycloalkyl or heterocyclyl, wherein the C3-8 cycloalkyl or heterocyclyl are optionally substituted with one or more R14;
• each R13 is independently —H, halogen, —CN, oxo, C1-6 alkyl, —OR20, —C(O)2R20, C3-8 cycloalkyl, heterocyclyl, heteroaryl, aryl, or —C(O)N(R22)(R22), wherein the C1-6 alkyl, aryl, or heteroaryl, is optionally substituted with one or more R15;
• each R14 is independently —C(O)OR20, —C(O)R20, —OR20, oxo, C1-6 alkyl, heterocycle, C3-8 cycloalkyl, or aryl, wherein the C1-6 alkyl, heterocycle, C3-8 cycloalkyl, or aryl is optionally substituted with one or more R16;
• or
• two R14 taken together can form a C3-6 cycloalkyl or heterocyclyl;
• each R15 is independently —H, C1-6 alkyl, C1-6 alkoxy, heteroaryl, aryl, —N(R22)(R22), —N(R22)C(O)OR22, or —N(R22)C(O)—U—N(R22)—Z;
• U is —(CH2)p—, —(CH2)p—Ar—, —CH═CH(CH2)p—, or heterocyclyl,
• Z is —R22 or —C(O)—U—N(R22)(R22);
• each R16 is independently C3-8 cycloalkyl, heterocyclyl, heteroaryl, or aryl, wherein the heterocyclyl, C3-8 cycloalkyl, heteroaryl, or aryl is optionally substituted with one or more R17;
• each R17 is independently —OR22, —N(R22)(R22), or —N(R22)C(O)—V—N(R22)-E;
• V is —(CH2)n—, —(CH2)n—Ar—, or —CH═CH(CH2)n—;
• E is —R22 or —C(O)—V—N(R22)(R22);
• Ar is aryl;
• each R18 is independently halogen, C1-6 alkyl, C3-6 cycloalkyl, —OR20, —N(R20)(R21), —C(O)R20, oxo, —N(R22)C(O)OR22, —N(R22)C(O)-Q-N(R22)—F, or —N(R22)-Q-N(R22)—F;
• Q is —CH═CH(CH2)m—, —(CH2)m—, —(CH2O)m—, —(CH2)m—Ar—, or —(CH2CH2O)o—(CH2)m—;
• F is —H, C1-6 alkyl, aryl, heteroaryl, —C(O)-Q-R22, or —C(O)-Q-N(R22)(R22), wherein the C1-6 alkyl, aryl, or heteroaryl is optionally substituted with one or more R22;
• or
• two R18 when on adjacent atoms may be taken together with the atoms to which they are each attached to form a C3-8 cycloalkyl or heterocyclic group optionally substituted with —OR21 or oxo;
• each R19 is independently —H, halogen, —OH, —NH2, oxo, —C(O)R20, —OR22, C3-6 cycloalkyl, or C1-6 alkyl;
• or
• two R19 when on adjacent atoms may be taken together with the atoms to which they are each attached to form an aryl or heteroaryl group optionally substituted with one or more R22;
• each R20 is independently —H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more —H, halogen, —CN, —OH, C1-6 alkyl, C1-6 alkoxy, C3-8 cycloalkyl, heterocyclyl, heteroaryl, or aryl;
• each R21 is independently —H, C1-6 alkyl, or —C(O)R22;
• each R22 is independently —H, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• each p is independently 1-4;
• each n is independently 1-4;
• each m is independently 1-4;
• and
• o is 1-3.