2. Academic Validation
  3. Discovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators

Discovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators

  • J Med Chem. 2019 Sep 12;62(17):8357-8363. doi: 10.1021/acs.jmedchem.9b00340.
Anthony B Pinkerton 1,  Satyamaheshwar Peddibhotla 1,  Fusayo Yamamoto 1,  Lauren M Slosky 2,  Yushi Bai 2,  Patrick Maloney 1,  Paul Hershberger 1,  Michael P Hedrick 1,  Bekhi Falter 1,  Robert J Ardecky 1,  Layton H Smith 1,  Thomas D Y Chung 1,  Michael R Jackson 1,  Marc G Caron 2,  Lawrence S Barak 2
Affiliations

Affiliations

  • 1 Conrad Prebys Center for Chemical Genomics , Sanford Burnham Prebys Medical Discovery Institute , La Jolla , California 92037 , United States.
  • 2 Duke University Medical Center , Durham , North Carolina 27709 , United States.
PMID: 31390201 DOI: 10.1021/acs.jmedchem.9b00340
Abstract

Neurotensin Receptor 1 (NTR1) is a G protein coupled receptor that is widely expressed throughout the central nervous system where it acts as a neuromodulator. Neurotensin receptors have been implicated in a wide variety of CNS disorders, but despite extensive efforts to develop small molecule ligands there are few reports of such compounds. Herein we describe the optimization of a quinazoline based lead to give 18 (SBI-553), a potent and brain penetrant NTR1 allosteric modulator.

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