Design and synthesis of tetrazole-based growth hormone secretagogue: the SAR studies of the O-benzyl serine side chain.

Abstract The structure–activity relationship of the O -benzyl serine side chain was investigated based on the tetrazole-based growth hormone secretagogue BMS-317180 ( 2 ). The ortho position of the benzyl moiety was found to be favorable for introduction of substituents. A series of ortho-substituted compounds were synthesized with improved in-vitro and in-vivo activity. Among them, the biphenyl compound 2p shows twofold improvement in potency compared to its parent compound BMS-317180 ( 2 ).