The known CD38 inhibitor 14 increased NAD+ levels in vitro and in vivo, but was developed for use in metabolic disease, and was not evaluated in the framework of cancer immunotherapy.19,20,48,49 We have explored a quinazoline dihydropyrimidine scaffold from a hit molecule, compound 1, previously identified by our laboratory as an inhibitor of CD38-hydolase activity.20 Preliminary SAR analysis of 12 commercially available or newly synthesized molecules, indicates that the dihydropyrimidine moiety (1–3) or its isosteric equivalent (4, 5 and 7) is optimal for activity. The gene discussed is CD38; the disease is metabolic disease.