2. Academic Validation
  3. 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

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

  • Bioorg Med Chem Lett. 2015 Jan 15;25(2):292-6. doi: 10.1016/j.bmcl.2014.11.047.
James B Thomas 1,  Angela M Giddings 2,  Srinivas Olepu 2,  Robert W Wiethe 2,  Danni L Harris 2,  Sanju Narayanan 2,  Keith R Warner 2,  Philippe Sarret 3,  Jean-Michel Longpre 3,  Scott P Runyon 2,  Brian P Gilmour 2
Affiliations

Affiliations

  • 1 Center for Organic and Medicinal Chemistry, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709, United States. Electronic address: jbthomas@rti.org.
  • 2 Center for Organic and Medicinal Chemistry, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709, United States.
  • 3 Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Ave. North, Sherbrooke, QC J1H 5N4, Canada.
PMID: 25499438 DOI: 10.1016/j.bmcl.2014.11.047
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).

Keywords

FLIPR assay; Levocabastine; NTS2 receptor; Neurotensin; Pain; SR142948a; SR48692.

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