Design, synthesis, and biological evaluation of phenylpropanamides as novel transient receptor potential valnilloid 1 antagonists

Synthesis and structure-activity relationship of N-benzyl-3-phenylpropanamides as transient receptor potential vanilloid 1 (TRPV1) antagonists are described. A variety of substituents such as halide, ester, nitro, and alkyl groups at 2 or 3-position of 4-(methylsulfonylamino) benzyl unit were examined. These compounds exhibited potent 45 Ca 2+ uptake inhibition in rat DRG neuron via TRPV1 blockade. Especially compound 28c , has been identified as a potent antagonist with IC 50 of 38 nM.