Synthesis and activity of novel indole derivatives as inhibitors of CD38

CD38 is a multifunctional enzyme/receptor expressed in a variety of mammalian tissues, regulating a wide range of physiological functions. Beginning with the previously reported compound 1, an inhibitor of human CD38 NADase, we synthesized a series of indole-based NH-substituted derivatives with modifications on alkyl chains, changes in substituent groups on aromatic rings, and differences in carbon chain lengths. Compounds 10, 13, 16 and 34 exhibited moderate inhibition of human CD38 NADase. Analysis of the structure-activity relationships showed that the phenylpropionyl moiety was very important for the inhibitory activity. This study provides information for the rational design of CD38 inhibitors.

Graphical abstractBased on an inhibitor of human CD38 NADase, we synthesized a series of indole-based NH-substituted derivatives with modifications on alkyl chains, changes in substituent groups on aromatic rings, and differences in carbon chain lengths. This study provides information for the rational design of CD38 inhibitors. Figure optionsDownload full-size imageDownload as PowerPoint slide