Novel benzodiazepines derivatives as analgesic modulating for Transient receptor potential vanilloid 1.

A new series of derivatives of 3-(7-chloro-5-(2-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)propanoic acid were designed and synthesized as analgesic modulating for Transient receptor potential vanilloid 1. They were investigated for TRPV1 antagonistic activity in vitro, analgesic activity and sedative activity in vivo and aqueous solubility. Preliminary studies identified 3-(7-chloro-5-(2-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-N,N-dimethylpropanamide(Compound 11), as a potent analgesic modulating for TRPV1 with potent activity and good aqueous solubility.