Identification of N-{[6-chloro-4-(2,6-dimethoxyphenyl)quinazolin-2-yl]carbonyl}-l-leucine (NTRC-808), a Novel Nonpeptide Chemotype Selective for the Neurotensin Receptor Type 2

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2014 Dec 16

PMID 25499438

Citations 2

Authors

James B Thomas

Angela M Giddings

Srinivas Olepu

Robert W Wiethe

Danni L Harris

Sanju Narayanan

Keith R Warner

Philippe Sarret

Jean-Michel Longpre

Scott P Runyon

Brian P Gilmour

Affiliations

Soon will be listed here.

Abstract

Compounds acting via the GPCR neurotensin receptor type 2 (NTS2) display analgesic effects in relevant animal models. Using a pharmacophore model based on known NT receptor nonpeptide compounds, we screened commercial databases to identify compounds that might possess activity at NTS2 receptor sites. Modification of our screening hit to include structural features known to be recognized by NTS1 and NTS2, led to the identification of the novel NTS2 selective nonpeptide, N-{[6-chloro-4-(2,6-dimethoxyphenyl)quinazolin-2-yl]carbonyl}-l-leucine (9). This compound is a potent partial agonist in the FLIPR assay with a profile of activity similar to that of the reference NTS2 analgesic nonpeptide levocabastine (5).

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