Synthesis and structural optimization of multiple H-bonding region of diarylalkyl (thio)amides as novel TRPV1 antagonists

Abstract Structural optimization of multiple H-bonding region and structure–activity relationship of diarylalkyl amides/thioamides as novel TRPV1 antagonists are described. In particular, we identified amide 34o and thioamides 35o and 35r , of which antagonistic activities were highly enhanced by an incorporation of cyano or vinyl-substituent to the multiple H-bonding region. They exhibited potent 45 Ca 2+ uptake inhibitions in rat DRG neuron with IC 50 s of 25, 32 and 28 nM, respectively.