Pi3 kinase inhibitors and methods of their use

A compound of Formula III, or a stereoisomer, tautomer, or solvate or pharmaceutically acceptable salt thereof;

• wherein:
• Q is O or S;
• V is O or S;
• L1 is CR9 or N;
• L2 is CR6 or N;
• R1 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, amino, substituted amino, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl, cycloalkyl, substituted cycloalkyl, substituted heterocyclyl, aryloxy, substituted aryloxy, heteroaryloxy, substituted heteroaryloxy, heterocyclyloxy, substituted heterocyclyloxy, cycloalkyloxy, substituted cycloalkyloxy, and alkylamino;
• R3, R7, and R9 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl, cycloalkyl, substituted cycloalkyl, substituted heterocyclyl, aryloxy, substituted aryloxy, heteroaryloxy, substituted heteroaryloxy, heterocyclyloxy, substituted heterocyclyloxy, cycloalkyloxy, substituted cycloalkyloxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester)amino, (carboxyl ester)oxy, cyano, halo, hydroxy, imino, nitro, SO3H, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthio, and substituted alkylthio;
• R4, R5, and R6 are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, amino, substituted amino, alkoxy, substituted alkoxy, alkyl, and substituted alkyl;
• R8 is selected from the group consisting of hydrogen, alkyl, —CO—R8a, substituted alkyl, and a three- to seven-membered ring selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl;
• and
• R8a is selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, amino, substituted amino, and alkylamino.

A compound of Formula IV, or a stereoisomer, tautomer, or solvate or pharmaceutically acceptable salt thereof,

• wherein,
• ring AD is selected from
• Q is O or S;
• L is CR9 or N;
• R1 represents —Z—Y—R10;
• Z is —NHCH2C(R11)R12—;
• Y is a bond or —CON(R13)—;
• R2, R3, R7, and R9 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl, cycloalkyl, substituted cycloalkyl, substituted heterocyclyl, aryloxy, substituted aryloxy, heteroaryloxy, substituted heteroaryloxy, heterocyclyloxy, substituted heterocyclyloxy, cycloalkyloxy, substituted cycloalkyloxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester)amino, (carboxyl ester)oxy, cyano, halo, hydroxy, nitro, SO3H, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthio, and substituted alkylthio;
• R4, R5, and R6 are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, amino, substituted amino, alkoxy, substituted alkoxy, alkyl, and substituted alkyl;
• R8 is selected from the group consisting of hydrogen, alkyl, —CO—R8a, substituted alkyl, and a three- to seven-membered ring selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl;
• and
• R8a is selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, amino, substituted amino, and alkylamino.
• R10 is C1-C6-alkylaminocarbonyl, C1-C6-alkoxycarbonyl, where each alkyl is independently optionally substituted by one or more halo, hydroxyl or C1-C6-alkoxy groups groups, or R10 is a mono-cyclic heteroaromatic ring having one or more ring heteroatoms selected from the group consisting of oxygen, nitrogen and sulphur, said ring being optionally substituted by one or more halo, hydroxyl, C1-C6-alkyl or C1-C6-alkoxy groups, where said alkyl and alkoxy are optionally further substituted by one or more halo, hydroxyl or C1-C6-alkoxy groups;
• R11 and R12 are independently selected from hydrogen, halo, hydroxy and C1-C6-alkyl where said alkyl group is optionally substituted by one or more halo, hydroxyl or C1-C6-alkoxy groups;
• and
• R13 is hydrogen or C1-C6-alkyl.