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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Thomas, James B.¹  Giddings, Angela M.¹  Olepu, Srinivas¹  Wiethe, Robert W.¹  Harris, Danni L.¹  Narayanan, Sanju¹  Warner, Keith R.¹  Sarret, Philippe²  Longpre, Jean-Michel²  Runyon, Scott P.¹  Gilmour, Brian P.¹ 

[1] Res Triangle Inst, Ctr Organ & Med Chem, Res Triangle Pk, NC 27709 USA

[2] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Physiol & Biophys, Sherbrooke, PQ J1H 5N4, Canada

关键词: Neurotensin;    NTS2 receptor;    Levocabastine;    SR142948a;    SR48692;    FLIPR assay;    Pain;   

DOI  :  10.1016/j.bmcl.2014.11.047

来源: Elsevier

【 摘 要 】

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). (C) 2014 Published by Elsevier Ltd.

【 授权许可】

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