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

Pinkerton, Anthony B; Peddibhotla, Satyamaheshwar; Yamamoto, Fusayo; Slosky, Lauren M; Bai, Yushi; Maloney, Patrick; Hershberger, Paul; Hedrick, Michael P; Falter, Bekhi; Ardecky, Robert J; Smith, Layton H; Chung, Thomas D Y; Jackson, Michael R; Caron, Marc G; Barak, Lawrence S

Pinkerton, Anthony B; Peddibhotla, Satyamaheshwar; Yamamoto, Fusayo; Slosky, Lauren M; Bai, Yushi; Maloney, Patrick; Hershberger, Paul; Hedrick, Michael P; Falter, Bekhi; Ardecky, Robert J; Smith, Layton H; Chung, Thomas D Y; Jackson, Michael R; Caron, Marc G; Barak, Lawrence S.

Affiliation

Pinkerton AB; Conrad Prebys Center for Chemical Genomics , Sanford Burnham Prebys Medical Discovery Institute , La Jolla , California 92037 , United States.
Peddibhotla S; Conrad Prebys Center for Chemical Genomics , Sanford Burnham Prebys Medical Discovery Institute , La Jolla , California 92037 , United States.
Yamamoto F; Conrad Prebys Center for Chemical Genomics , Sanford Burnham Prebys Medical Discovery Institute , La Jolla , California 92037 , United States.
Slosky LM; Duke University Medical Center , Durham , North Carolina 27709 , United States.
Bai Y; Duke University Medical Center , Durham , North Carolina 27709 , United States.
Maloney P; Conrad Prebys Center for Chemical Genomics , Sanford Burnham Prebys Medical Discovery Institute , La Jolla , California 92037 , United States.
Hershberger P; Conrad Prebys Center for Chemical Genomics , Sanford Burnham Prebys Medical Discovery Institute , La Jolla , California 92037 , United States.
Hedrick MP; Conrad Prebys Center for Chemical Genomics , Sanford Burnham Prebys Medical Discovery Institute , La Jolla , California 92037 , United States.
Falter B; Conrad Prebys Center for Chemical Genomics , Sanford Burnham Prebys Medical Discovery Institute , La Jolla , California 92037 , United States.
Ardecky RJ; Conrad Prebys Center for Chemical Genomics , Sanford Burnham Prebys Medical Discovery Institute , La Jolla , California 92037 , United States.
Smith LH; Conrad Prebys Center for Chemical Genomics , Sanford Burnham Prebys Medical Discovery Institute , La Jolla , California 92037 , United States.
Chung TDY; Conrad Prebys Center for Chemical Genomics , Sanford Burnham Prebys Medical Discovery Institute , La Jolla , California 92037 , United States.
Jackson MR; Conrad Prebys Center for Chemical Genomics , Sanford Burnham Prebys Medical Discovery Institute , La Jolla , California 92037 , United States.
Caron MG; Duke University Medical Center , Durham , North Carolina 27709 , United States.
Barak LS; Duke University Medical Center , Durham , North Carolina 27709 , United States.

J Med Chem ; 62(17): 8357-8363, 2019 09 12.

Article de En | MEDLINE | ID: mdl-31390201

ABSTRACT

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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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Quinazolines / Maladies du système nerveux central / Récepteur neurotensine / Découverte de médicament / Bêta-Arrestines Limites: Animals Langue: En Journal: J Med Chem Sujet du journal: QUIMICA Année: 2019 Type de document: Article Pays d'affiliation: États-Unis d'Amérique

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