Abstract: Compounds having activity as modulators of phosphodiesterase 7 (PDE 7) are provided. The compounds have the following Structures (I) or (II): as a stereoisomer, enantiomer, or tautomer thereof or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein each of R1, R2, R3, R4a, R4b, ring A, ring B, ring A? and ring B? (i.e., {circle around (A)}, {circle around (B)}, , and as shown in Structure (I) and (II), respectively) are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of phosphodiesterase 7 (PDE 7) are also provided.

Abstract: Compounds, compositions, and methods for generating T cells with altered phenotype are disclosed. The phenotype-altered T cells have increased persistence, prolonged survival, and increased antitumor activity and are useful for treatment of cancers.

Abstract: Pyrimido[4,5-g]quinazoline quinone derivatives were synthesized as anthranone-like reductive alkylating agents. Like many naturally-occurring antibiotics, these quinone derivatives are designed to afford an alkylating quinone methide species upon reduction and leaving group elimination. Kinetic studies of pyrimido[4,5-g]quinazoline hydroquinones provided evidence of quinone methide intermediates able to trap nucleophiles (alkylation) and protons. The rate of quinone methide formation is determined by the hydroquinone free energy. Thus, a linear free energy relationship for quinone methide formation was obtained by plotting rates of quinone methide formation, as the log, versus the quinone reduction potential. The pyrimido[4-5-g]quinazoline quinone methides fall on this free energy plot, showing that these species are formed by the same mechanism as the other structurally-diverse quinone methides previously studied in this research group.