Scholars@Duke
Journal cover image

Imidazole-derived agonists for the neurotensin 1 receptor.

Publication ,  Journal Article
Hershberger, PM; Hedrick, MP; Peddibhotla, S; Mangravita-Novo, A; Gosalia, P; Li, Y; Gray, W; Vicchiarelli, M; Smith, LH; Chung, TDY; Caron, MG ...
Published in: Bioorg Med Chem Lett
January 1, 2014
Published version (DOI) Link to item

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.

Duke Scholars

Lawrence Simeon Barak
Author Lawrence Simeon Barak Cell Biology
Altmetric Attention Stats
Dimensions Citation Stats

Published In

Bioorg Med Chem Lett

DOI

10.1016/j.bmcl.2013.11.026

EISSN

1464-3405

Publication Date

January 1, 2014

Volume

24

Issue

1

Start / End Page

262 / 267

Location

England

Related Subject Headings

  • Structure-Activity Relationship
  • Receptors, Neurotensin
  • Molecular Structure
  • Mice
  • Medicinal & Biomolecular Chemistry
  • Imidazoles
  • Humans
  • Dose-Response Relationship, Drug
  • Animals
  • 3405 Organic chemistry
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hershberger, P. M., Hedrick, M. P., Peddibhotla, S., Mangravita-Novo, A., Gosalia, P., Li, Y., … Roth, G. P. (2014). Imidazole-derived agonists for the neurotensin 1 receptor. Bioorg Med Chem Lett, 24(1), 262–267. https://doi.org/10.1016/j.bmcl.2013.11.026
Hershberger, Paul M., Michael P. Hedrick, Satyamaheshwar Peddibhotla, Arianna Mangravita-Novo, Palak Gosalia, Yujie Li, Wilson Gray, et al. “Imidazole-derived agonists for the neurotensin 1 receptor.” Bioorg Med Chem Lett 24, no. 1 (January 1, 2014): 262–67. https://doi.org/10.1016/j.bmcl.2013.11.026.
Hershberger PM, Hedrick MP, Peddibhotla S, Mangravita-Novo A, Gosalia P, Li Y, et al. Imidazole-derived agonists for the neurotensin 1 receptor. Bioorg Med Chem Lett. 2014 Jan 1;24(1):262–7.
Hershberger, Paul M., et al. “Imidazole-derived agonists for the neurotensin 1 receptor.” Bioorg Med Chem Lett, vol. 24, no. 1, Jan. 2014, pp. 262–67. Pubmed, doi:10.1016/j.bmcl.2013.11.026.
Hershberger PM, Hedrick MP, Peddibhotla S, Mangravita-Novo A, Gosalia P, Li Y, Gray W, Vicchiarelli M, Smith LH, Chung TDY, Thomas JB, Caron MG, Pinkerton AB, Barak LS, Roth GP. Imidazole-derived agonists for the neurotensin 1 receptor. Bioorg Med Chem Lett. 2014 Jan 1;24(1):262–267.
Journal cover image

Published In

Bioorg Med Chem Lett

DOI

10.1016/j.bmcl.2013.11.026

EISSN

1464-3405

Publication Date

January 1, 2014

Volume

24

Issue

1

Start / End Page

262 / 267

Location

England

Related Subject Headings

  • Structure-Activity Relationship
  • Receptors, Neurotensin
  • Molecular Structure
  • Mice
  • Medicinal & Biomolecular Chemistry
  • Imidazoles
  • Humans
  • Dose-Response Relationship, Drug
  • Animals
  • 3405 Organic chemistry