Design, synthesis and pharmacological test of a quinoline based, nonpeptidic analogue of neurotensin(8–13)

Abstract

The design, synthesis and pharmacological testing of a quinoline based, nonpeptidic analogue of neurotensin(8–13) using our reported multiple template approach to developing nonpeptidic mimetics of neuropeptides are reported. The newly synthesized quinoline analogue is found to be less active in binding to the neurotensin receptors than previously reported mimetics-1 and -2 which are partial nonpeptidic analogues of neurotensin(8–13). However, the present study led to the discovery of a mistake in a literature procedure for alkylation at position-3 of ethyl indole-2-carboxylate and a consequent mistake in the synthesis of mimics-1 and -2. With the computational and experimental results of the quinoline analogue, along with mimics-1 and -2 with the correct structures, which, accordingly, served as a blind test for the multiple template approach, the concept of this approach has been experimentally validated.