Literature DB >> 24332089

Imidazole-derived agonists for the neurotensin 1 receptor.

Paul M Hershberger1, Michael P Hedrick2, Satyamaheshwar Peddibhotla3, Arianna Mangravita-Novo3, Palak Gosalia2, Yujie Li2, Wilson Gray2, Michael Vicchiarelli3, Layton H Smith3, Thomas D Y Chung2, James B Thomas4, Marc G Caron5, Anthony B Pinkerton2, Lawrence S Barak5, Gregory P Roth3.   

Abstract

A scaffold-hop program seeking full agonists of the neurotensin-1 (NTR1) receptor identified the probe molecule ML301 (1) and associated analogs, including its naphthyl analog (14) which exhibited similar properties. Compound 1 showed full agonist behavior (79-93%) with an EC50 of 2.0-4.1μM against NTR1. Compound 1 also showed good activity in a Ca mobilization FLIPR assay (93% efficacy at 298nM), consistent with it functioning via the Gq coupled pathway, and good selectivity relative to NTR2 and GPR35. In further profiling, 1 showed low potential for promiscuity and good overall pharmacological data. This report describes the discovery, synthesis, and SAR of 1 and associated analogs. Initial in vitro pharmacologic characterization is also presented.
Copyright © 2013 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Agonist; Imidazole; Methamphetamine; Neurotensin 1

Mesh：

Substances：

Year:  2013        PMID： 24332089      PMCID： PMC3898338          DOI： 10.1016/j.bmcl.2013.11.026

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  19 in total

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