Pyridine and pyridimine compounds as PI3K-gamma inhibitors

A method of treating a disease or disorder in a patient, wherein said disease or disorder is associated with abnormal expression or activity of PI3Kγ kinase, wherein the disease or disorder is selected from cancer or tumors, sarcomas, lymphomas, and leukemias, the method comprising administering to said patient a therapeutically effective amount of a compound of Formula IIb:

• or a pharmaceutically acceptable salt or tautomer thereof, wherein:
• R1 is independently selected from halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, Cy1a, —C1-4 alkylene-Cy, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcORd, NRcC(O)Rb, NRcC(O)ORb, NRcC(O)NRcRd, NRcS(O)Rb, NRcS(O)2Rb NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, and S(O)2NRcRd;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-4 haloalkyl are optionally substituted with 1, 2, or 3 independently selected R11 groups;
• R3 is selected from H, C1-6 alkyl, C1-4 haloalkyl, Cy1, C(O)NRc1Rd1, and C(O)ORa1, wherein said C1-6 alkyl is optionally substituted with 1, 2, or 3 independently selected R13 groups;
• R4 is selected from H, C1-6 alkyl, C1-4 haloalkyl, Cy1, —C1-4 alkylene-Cy1, NRc1Rd1, and NRc1C(O)Rb1, wherein said C1-6 alkyl is optionally substituted with 1, 2, or 3 independently selected R13 groups;
• each R11 is independently selected from halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, Cy2, —C1-4 alkylene-Cy2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2ORd2, NRc2C(O)Rb2, NRc2C(O)ORa2 NRc2C(O)NRc2Rd2 NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-4 haloalkyl are each optionally substituted with 1, 2, or 3 independently selected Rg groups;
• each R13 is independently selected from halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, Cy3, —C1-4 alkylene-Cy3, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3ORd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-4 haloalkyl are each optionally substituted with 1, 2, or 3independently selected Rg groups;
• Cy1a is selected from 5-6 membered heterocycloalkyl having 1 or 2 ring atoms independently selected from N and O, which is optionally substituted by 1, 2, or 3 independently selected R11 groups;
• each Cy is independently selected from 3-6 membered cycloalkyl, phenyl, 5-6 membered heteroaryl having 1 or 2 ring atoms independently selected from N and O, and 4-8 membered heterocycloalkyl having 1 or 2 ring atoms independently selected from N and O, each of which is optionally substituted by 1, 2, or 3 independently selected R11 groups;
• each Cy1 is independently selected from 3-10 membered cycloalkyl, 6-9 membered aryl, 5-6 membered heteroaryl having 1 or 2 ring atoms independently selected from N and O, and 5-6 membered heterocycloalkyl having 1 ring atom selected from N, O, and S, each of which is optionally substituted by 1, 2, or 3 independently selected R13 groups;
• each Cy2 is independently selected from 3-6 membered cycloalkyl, phenyl, 5-6 membered heteroaryl having 1 or 2 ring atoms independently selected from N and O, and 5-6 membered heterocycloalkyl having 1 or 2 ring atoms independently selected from N and O, each of which is optionally substituted by 1, 2, or 3 independently selected Rg groups;
• each Cy3 is independently selected from 3-6 membered cycloalkyl, phenyl, and 5-6 membered heterocycloalkyl having 1 ring atom selected from N and O, each of which is optionally substituted by 1, 2, or 3 independently selected Rg groups;
• Ra, Rc, and Rd are each independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, Cy, and —C1-4 alkylene-Cy;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-4 haloalkyl are each optionally substituted with 1, 2, or 3 independently selected R11 groups;
• Rb is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, Cy, and —C1-4 alkylene-Cy;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-4 haloalkyl are each optionally substituted with 1, 2, or 3 independently selected R11 groups;
• alternatively, any Rc and Rd attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group having 1 or 2 ring atoms independently selected from N and O, optionally substituted with 1, 2, or 3 independently selected R11 groups;
• Ra1, Rc1, and Rd1 are each independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, Cy1, and —C1-4 alkylene-Cy1;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-4 haloalkyl are each optionally substituted with 1, 2, or 3 independently selected R13 groups;
• Rb1 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, Cy1, and —C1-4 alkylene-Cy1;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-4 haloalkyl are each optionally substituted with 1, 2, or 3 independently selected R13 groups;
• or
• alternatively, any Rc1 and Rd1 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, or 6-membered heterocycloalkyl group having 1 or 2 ring atoms independently selected from N and O optionally substituted with 1, 2 or 3 independently selected R13 groups;
• each Ra2, Rc2, and Rd2 are independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, Cy2, and —C1-4 alkylene-Cy2;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-4 haloalkyl are each optionally substituted with 1, 2, or 3 independently selected Rg groups;
• each Rb2 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, Cy2, and —C1-4 alkylene-Cy2;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-4 haloalkyl are each optionally substituted with 1, 2, or 3 independently selected Rg groups;
• or
• each Ra3, Rc3, and Rd3 are independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, Cy3, and —C1-4 alkylene-Cy3;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-4 haloalkyl are each optionally substituted with 1, 2, or 3 independently selected Rg groups;
• each Rb3 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, Cy3, and —C1-4 alkylene-Cy3;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-4 haloalkyl are each optionally substituted with 1, 2, or 3 independently selected Rg groups;
• or
• alternatively, any Rc3 and Rd3 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group having 1 or 2 ring atoms independently selected from N and O optionally substituted with 1, 2 or 3 independently selected Rg groups;
• and
• each Rg is independently selected from OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-C1-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino.