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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Administration, Oral
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Allosteric Regulation / drug effects
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Animals
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Biological Availability
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Central Nervous System Diseases / drug therapy*
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Central Nervous System Diseases / metabolism
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Dopamine Plasma Membrane Transport Proteins / deficiency
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Dopamine Plasma Membrane Transport Proteins / metabolism
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Dose-Response Relationship, Drug
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Drug Discovery*
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Female
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Locomotion / drug effects
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Structure
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Quinazolines / administration & dosage
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Quinazolines / chemistry
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Quinazolines / pharmacology*
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Rats
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Receptors, Neurotensin / antagonists & inhibitors*
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Receptors, Neurotensin / metabolism
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Structure-Activity Relationship
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beta-Arrestins / administration & dosage
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beta-Arrestins / chemistry
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beta-Arrestins / pharmacology*
Substances
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Dopamine Plasma Membrane Transport Proteins
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Quinazolines
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Receptors, Neurotensin
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beta-Arrestins
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neurotensin type 1 receptor