On the inhibition of capsaicin response in dorsal root ganglion neurons by nobilamide B and analogues: a structure–activity relationship study

摘要

Nobilamide B, a TRPV1 antagonist, and a series of Ala-substituted analogues were synthesized and their neuroactivity was assessed in a primary culture of dorsal root ganglion (DRG) neurons. Analogues >4, >6, and >7 showed comparable activity, affecting capsaicin response in neurons, in contrast to >2, >3, and >5 which showed minimal blocking. Compounds >2, >3, and >5 correspond to analogues in which d-Phe, d-Leu and d-allo-Thr have been substituted with Ala, respectively. The observed loss of bioactivity in these three analogues highlights the importance of d amino acids in the primary structure of nobilamide B.