Discovery of 4-(5-Methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a Novel α7 Nicotinic Acetylcholine Receptor Agonist for the Treatment of Cognitive Disorders in Schizophrenia: Synthesis, SAR Development, and in Vivo Efficacy in Cognition Models

Christopher J O'DONNELL; Bruce N ROGERS; Raymond S HURST; Noha MAKLAD; Robert J MATHER; Stafford MCLEAN; Frank M NEDZA; Brian T O'NEILL; LANGU PENG; WEIMIN QIAN; Melinda M ROTTAS; Steven B SANDS; Brian S BRONK; Anne W SCHMIDT; Alka V SHRIKHANDE; Douglas K SPRACKLIN; Diane F WONG; Andy ZHANG; LEI ZHANG; Dianne K BRYCE; Jotham W COE; Karen K COOK; Allen J DUPLANTIER; Edelweiss EVRARD; Mihaly HAJOS; William E HOFFMANN

doi:10.1021/jm9015075

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Discovery of 4-(5-Methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a Novel α7 Nicotinic Acetylcholine Receptor Agonist for the Treatment of Cognitive Disorders in Schizophrenia: Synthesis, SAR Development, and in Vivo Efficacy in Cognition Models

Journal article

Peer reviewed

Discovery of 4-(5-Methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a Novel α7 Nicotinic Acetylcholine Receptor Agonist for the Treatment of Cognitive Disorders in Schizophrenia: Synthesis, SAR Development, and in Vivo Efficacy in Cognition Models

Christopher J O'DONNELL, Bruce N ROGERS, Raymond S HURST, Noha MAKLAD, Robert J MATHER, Stafford MCLEAN, Frank M NEDZA, Brian T O'NEILL, LANGU PENG, WEIMIN QIAN, …

Journal of medicinal chemistry, Vol.53(3), pp.1222-1237

2010

DOI: 10.1021/jm9015075

PMID: 20043678

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Abstract

A novel alpha 7 nAChR agonist, 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (24, CP-810,123), has been identified as a potential treatment for cognitive deficits associated with psychiatric or neurological conditions including schizophrenia and Alzheimer's disease. Compound 24 is a potent and selective compound with excellent pharmaceutical properties. In rodent, the compound displays high oral bioavailability and excellent brain penetration affording high levels of receptor occupancy and in vivo efficacy in auditory sensory gating and novel object recognition. The structural diversity of this compound and its preclinical in vitro and in vivo package support the hypothesis that alpha 7 nAChR agonists may have potential as a pharmacotherapy for the treatment of cognitive deficits in schizophrenia.

Neuropharmacology

Psychopharmacology

Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer

Psychology. Psychoanalysis. Psychiatry

Neurotransmitters. Neurotransmission. Receptors

Pharmacology. Drug treatments

Biological and medical sciences

Cholinergic system

Medical sciences

Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)

Details

Title: Subtitle: Discovery of 4-(5-Methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a Novel α7 Nicotinic Acetylcholine Receptor Agonist for the Treatment of Cognitive Disorders in Schizophrenia: Synthesis, SAR Development, and in Vivo Efficacy in Cognition Models
Creators: Christopher J O'DONNELL - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Bruce N ROGERS - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Raymond S HURST - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Noha MAKLAD - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Robert J MATHER - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Stafford MCLEAN - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Frank M NEDZA - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Brian T O'NEILL - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
LANGU PENG - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
WEIMIN QIAN - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Melinda M ROTTAS - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Steven B SANDS - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Brian S BRONK - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Anne W SCHMIDT - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Alka V SHRIKHANDE - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Douglas K SPRACKLIN - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Diane F WONG - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Andy ZHANG - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
LEI ZHANG - Pfizer (United States)
Dianne K BRYCE - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Jotham W COE - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Karen K COOK - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Allen J DUPLANTIER - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Edelweiss EVRARD - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Mihaly HAJOS - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
William E HOFFMANN - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, United States
Resource Type: Journal article
Publication Details: Journal of medicinal chemistry, Vol.53(3), pp.1222-1237
DOI: 10.1021/jm9015075
PMID: 20043678
NLM abbreviation: J Med Chem
ISSN: 0022-2623
eISSN: 1520-4804
Publisher: American Chemical Society
Language: English
Date published: 2010
Academic Unit: Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094349102771

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