Open AccessDiscovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators
Author(s) -
Anthony B. Pinkerton,
Satyamaheshwar Peddibhotla,
Fusayo Yamamoto,
Lauren M. Slosky,
Yushi Bai,
Patrick Maloney,
Paul Hershberger,
Michael Hedrick,
Bekhi Falter,
Robert Ardecky,
Layton H. Smith,
Thomas D.Y. Chung,
Michael R. Jackson,
Marc G. Caron,
Lawrence S Barak
Publication year - 2019
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.9b00340
Subject(s) - penetrant (biochemical) , allosteric regulation , chemistry , neurotensin , allosteric modulator , receptor , neurotensin receptor , pharmacology , central nervous system , neuroscience , biochemistry , neuropeptide , biology , organic chemistry
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.