Discovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators.
Administration, Oral
Allosteric Regulation
/ drug effects
Animals
Biological Availability
Central Nervous System Diseases
/ drug therapy
Dopamine Plasma Membrane Transport Proteins
/ deficiency
Dose-Response Relationship, Drug
Drug Discovery
Female
Locomotion
/ drug effects
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Structure
Quinazolines
/ administration & dosage
Rats
Receptors, Neurotensin
/ antagonists & inhibitors
Structure-Activity Relationship
beta-Arrestins
/ administration & dosage
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
12 09 2019
12 09 2019
Historique:
pubmed:
8
8
2019
medline:
1
7
2020
entrez:
8
8
2019
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 31390201
doi: 10.1021/acs.jmedchem.9b00340
pmc: PMC7003992
mid: NIHMS1046925
doi:
Substances chimiques
Dopamine Plasma Membrane Transport Proteins
0
Quinazolines
0
Receptors, Neurotensin
0
beta-Arrestins
0
neurotensin type 1 receptor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
8357-8363Subventions
Organisme : NIDA NIH HHS
ID : P30 DA029925
Pays : United States
Organisme : NIDA NIH HHS
ID : R33 DA038019
Pays : United States
Organisme : NIDA NIH HHS
ID : F32 DA043931
Pays : United States
Organisme : NIDA NIH HHS
ID : K99 DA048970
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA038019
Pays : United States
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