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 content:0.322 μmol/10 6 cell) showed better cellular lactate production activity than UK-5099 (LA content:0.185 μmol/10 6 cell). Further compound 4i was also tested on shaved mice by topical treatment and promoted obvious hair growth on mice.