Aminopyridine derivatives as phosphatidylinositol phosphate kinase inhibitors

A compound of Formula (Ie):

• or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, stereoisomer, or tautomer thereof,
• wherein:
• represents a double bond;
• A is C3-8 cycloalkyl, C4-8 cycloalkenyl, aryl, spiroheterocyclyl, heterocyclyl, or 6-membered heteroaryl;
• a, b, c, and d, are each independently C, CH, or N, wherein at least one of a, b, c, and d is N;
• and no more than two of a, b, c, and d are N;
• X4 and Z1 are each independently —O—, —N(R15)—, or —C(R15)(R15)—;
• ω is 1, 2, or 3;
• W is C(R6) or N;
• R1 is —N(R2)C(O)R3, —C(O)N(R2)(R3), —S(O)2N(R2)(R3), —N(R2)S(O)2R3, —R2C(O)N(R2)(Rc3), or heteroaryl, wherein heteroaryl is optionally substituted with one or more R7;
• R2 is independently, at each occurrence, 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 R4;
• R3 is 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 R4;
• or
• R2 and R3 when taken together with the atom to which they are each attached form a heterocycle optionally substituted with one or more R4;
• R4 is independently, at each occurrence, —H, halogen, —OH, —NH2, —NO2, —CN, C1-6 alkyl, C1-6 alkoxy, C3-8 cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C3-8 cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R7;
• R5 is —H, halogen, —OH, —CN, C1-6 alkyl, methoxy, —O—C3-C6 alkyl, C3-8 cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• R6 is —H, halogen, —OH, —NH2, —NO2, —CN, —CO2H, —C(O)NH2, C1-6 alkoxy, C3-8 cycloalkyl, heterocyclyl, —O—C3-8 cycloalkyl, or C1-6 alkyl, wherein the C1-6 alkyl, C1-6 alkoxy, heterocyclyl, or C3-8 cycloalkyl is optionally substituted with —OH, C1-6 alkyl, C1-6 alkoxy, C3-8 cycloalkyl, —NH2, —NH(C1-6 alkyl), or —N(C1-6 alkyl)2;
• or
• R5 and R6 when taken together with the carbon atom to which they are each attached form a 5- to 6-membered heteroaryl ring;
• R7 is independently, at each occurrence, —H, halogen, —OH, C1-6 alkyl, C1-6 alkoxy, C3-8 cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C3-8 cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R14;
• R14 is independently, at each occurrence, —H, halogen, —CN, —NO2, —OH, —NH2, C1-6 alkyl, C3-8 cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• R15 is independently, at each occurrence, —H, halogen, oxo, —OH, —NH2, —NO2, C1-6 alkyl, C1-6 alkoxy, C3-8 cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)N(R21)(R23), —(CH2)o—C(O)R23, —OC(O)R23, —C(O)OR23, —SO2R23, —N(R23)C(O)—Ar—N(R23)-G, or —N(R23)C(O)—Ar—N(R23)C(O)-G, wherein the C1-6 alkyl, C1-6 alkoxy, C3-8 cycloalkyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R23;
• or
• two R15 groups, together with the atoms to which they are attached, form a heterocyclyl, C3-6 cycloalkyl, C5-6 spirocycloalkyl, aryl, or heteroaryl, wherein the C3-6 cycloalkyl, heterocyclyl, C5-6 spirocycloalkyl, heteroaryl, or aryl is optionally substituted with one or more R20;
• Ar is aryl;
• G is —H, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)OR23, —C(O)CH═CHCH2N(R23)(R23), or —C(O)N(R21)(R23);
• or
• two R15 when on adjacent atoms may be taken together with the atoms to which they are each attached to form a heterocycle optionally substituted with one or more R16;
• R16 is independently, at each occurrence, C1-6 alkyl, C3-6 cycloalkyl, —C(O)R23, —C(O)R23, —C(O)OR23, —S(O)2R23, or oxo;
• R20 is independently, at each occurrence, —H, halogen, —OH, —NH2, oxo, —C(O)R21, —OR23, C3-6 cycloalkyl, or C1-6 alkyl;
• R21 is independently, at each occurrence, —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 R23 is independently, at each occurrence, —H, C1-6 alkyl, C1-6 alkoxy, 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, —NH2, C1-6 alkyl, C1-6 alkoxy, C3-8 cycloalkyl, heterocyclyl, heteroaryl, aryl, or R24;
• R24 is independently, at each occurrence, —H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, heterocyclyl, aryl, heteroaryl, C(O)N(C1-6 alkyl)(C1-6 alkyl), —C(O)—C1-6 alkyl, —C(O)—C2-6 alkenyl, or —C(O)O—C1-6 alkyl, 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, —NH2, C1-6 alkyl, C1-6 alkoxy, C3-8 cycloalkyl, heterocyclyl, heteroaryl, or aryl;
• and
• each o is independently 0-4.