Design, synthesis and biological evaluation of novel cyano-cinnamate derivatives as mitochondrial pyruvate carrier inhibitors.

ABSTRACT

Mitochondrial pyruvate carrier (MPC) inhibitors promote the development of hair follicle stem cells without affecting normal cells, which is promising for the treatment of hair loss. Herein, a series of cyano-cinnamate derivatives of UK-5099 were designed and synthesized. All these new compounds have been tested for their ability to promote cellular lactate production in vitro. Compound 4i (LA content0.322 µmol/106cell) showed better cellular lactate production activity than UK-5099 (LA content0.185 µmol/106cell). Further compound 4i was also tested on shaved mice by topical treatment and promoted obvious hair growth on mice.