Phosphoinositide 3-kinase inhibitor compounds and methods of use

A compound selected from Formula Ia and Formula Ib:

• and stereoisomers, geometric isomers, tautomers, solvates, metabolites, and pharmaceutically acceptable salts thereof, wherein:
• X is O or S;
• R1 is selected from H, F, Cl, Br, I, CN, —CR14R15—NR16R17, —CR14R15—NHR10, —(CR14R15)tNR10R11, —C(R14R15)nNR12C(═Y)R10, —(CR14R15)nNR12S(O)2R10, —(CR14R15)mOR10, —(CR14R15)nS(O)2R10, —(CR14R15)nS(O)2NR10R11, —C(OR10)R11R14, —C(R14)═CR18R19, —C(═Y)R10, —C(═Y)OR10, —C(═Y)NR10R11, —C(═Y)NR12OR10, —C(═O)NR12S(O)2R10, —C(═O)NR12(CR14R15)mNR10R11, —NO2, —NHR12, —NR12C(═Y)R11, —NR12C(═Y)OR11, —NR12C(═Y)NR10R11, —NR12S(O)2R10, —NR12SO2NR10R11, —S(O)2R10, —S(O)2NR10R11, —SC(═Y)R10, —SC(═Y)OR10, C2-C12 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C12 carbocyclyl, C2-C20 heterocyclyl, C6-C20 aryl, or C1-C20 heteroaryl;
• R2 is selected from H, F, Cl, Br, I, CN, CF3, —NO2, —C(═Y)R10, —C(═Y)OR10, —C(═Y)NR10R11, —(CR14R15)mNR10R11, —(CR14R15)nOR10, —(CR14R15)t—NR12C(═O)(CR14R15)NR10R11, —NR12C(═Y)R10, —NR12C(═Y)OR10, —NR12C(═Y)NR10R11, —NR12SO2R10, OR10, —OC(═Y)R10, —OC(═Y)OR10, —OC(═Y)NR10R11, —OS(O)2(OR10), —OP(═Y)(OR10)(OR11), —OP(OR10)(OR11), SR10, —S(O)R10, —S(O)2R10, —S(O)2NR10R11, —S(O)(OR10), —S(O)2(OR10), —SC(═Y)R10, —SC(═Y)OR10, —SC(═Y)NR10R11, C1-C12 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C12 carbocyclyl, C2-C20 heterocyclyl, C6-C20 aryl, and C1-C20 heteroaryl;
• R3 is fused bicyclic C4-C20 heterocyclyl or fused bicyclic C1-C20 heteroaryl;
• R10, R11 and R12 are independently H, C1-C12 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C12 carbocyclyl, C2-C20 heterocyclyl, C6-C20 aryl, or C1-C20 heteroaryl,
• or R10 and R11 together with the nitrogen to which they are attached optionally form a saturated, partially unsaturated or fully unsaturated C3-C20 heterocyclic ring optionally containing one or more additional ring atoms selected from N, O or S, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, (CH2)mOR10, NR10R11, CF3, F, Cl, Br, I, SO2R10, C(═O)R10, NR12C(═Y)R11, NR12S(O)2R11, C(═Y)NR10R11, C1-C12 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C12 carbocyclyl, C2-C20 heterocyclyl, C6-C20 aryl and C1-C20 heteroaryl;
• R14 and R15 are independently selected from H, C1-C12 alkyl, or —(CH2)n-aryl,
• or R14 and R15 together with the atoms to which they are attached form a saturated or partially unsaturated C3-C12 carbocyclic ring,
• R16 and R17 are independently H, C1-C12 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C12 carbocyclyl, or C6-C20 aryl,
• R18 and R19 together with the carbon to which they are attached form a C3-C20 heterocyclic ring,
• where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C4-C20 heterocyclyl, and fused bicyclic C1-C20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF3, —NO2, oxo, R10, —C(═Y)R10, —C(═Y)OR10, —C(═Y)NR10R11, —(CR14R15)nNR10R11, —(CR14R15)nOR10, —NR10R11, —NR12C(═Y)R10, —NR12C(═Y)OR11, —NR12C(═Y)NR10R11, —NR12SO2R10, ═NR12, OR10, —OC(═Y)R10, —OC(═Y)OR10, —OC(═Y)NR10R11, —OS(O)2(OR10), —OP(═Y)(OR10)(OR11), —OP(OR10)(OR11), SR10, —S(O)R10, —S(O)2R10, —S(O)2NR10R11, —S(O)(OR10), —S(O)2(OR10), —SC(═Y)R10, —SC(═Y)OR10, —SC(═Y)NR10R11, C1-C12 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C12 optionally substituted carbocyclyl, C2-C20 optionally substituted heterocyclyl, C6-C20 optionally substituted aryl, C1-C20 optionally substituted heteroaryl, —(CR14R15)t—NR12C(═O)(CR14R15)NR10R11, and (CR4R5)t—NR10R11;
• Y is O, S, or NR12;
• m is 0, 1, 2, 3, 4, 5 or 6;
• n is 1, 2, 3, 4, 5 or 6;
• and
• t is 2, 3, 4, 5 or 6.