Synthesis and biological evaluation of novel sulfonamide derivatives of tricyclic thieno[2,3-d]pyrimidin-4(3H)-ones on melanin synthesis in murine B16 cells

Abstract

Phototherapy with psoralens as photosensitizers is the commonly used method for the treatment of vitiligo. Considering the structure similarity between psoralens and thieno[2,3-d]pyrimidinones, a series of novel sulfonamide derivatives containing tricyclic thieno[2,3-d]pyrimidinone were synthesized and evaluated for melanin synthesis in murine B16 cells. All new compounds were characterized by 1H NMR, 13C NMR, IR and HRMS (ESI). Among them, 6 compounds demonstrated excellent activity than positive control (8-methoxylpsoralen, 8-MOP) with more than 1.5-fold potency. Compound 11w with dichloro substitution at meta-positions in the benzenesulfonyl moiety was the most potent one (658.3 ± 8.7%), exhibiting 5.0-fold stronger activity than 8-MOP (130.9 ± 8.6%). The difluoro analog compound 11o increased melanin synthesis in murine B16 cells with a 4.35-fold potency as compared to 8-MOP. These compounds may serve as lead compounds for further drug discoveries for the treatment of vitiligo.