J Med Chem. 2010 Feb 11;53(3):1222-37.

Discovery of 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a novel alpha 7 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders in schizophrenia: synthesis, SAR development, and in vivo efficacy in cognition models.

Source

Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, USA. christopher.j.odonnell@pfizer.com

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.

PMID:: 20043678; [PubMed - indexed for MEDLINE]

MeSH Terms, Substances

MeSH Terms

Substances

LinkOut - more resources

Full Text Sources

Supplemental Content

Save items

Related citations in PubMed

Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: synthesis and structure--activity relationship. [J Med Chem. 2006]
Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: synthesis and structure--activity relationship.
Wishka DG, Walker DP, Yates KM, Reitz SC, Jia S, Myers JK, Olson KL, Jacobsen EJ, Wolfe ML, Groppi VE, et al. J Med Chem. 2006 Jul 13; 49(14):4425-36.
(R)-3'-(3-methylbenzo[b]thiophen-5-yl)spiro[1-azabicyclo[2,2,2]octane-3,5'-oxazolidin]-2'-one, a novel and potent alpha7 nicotinic acetylcholine receptor partial agonist displays cognitive enhancing properties. [J Med Chem. 2006]
(R)-3'-(3-methylbenzo[b]thiophen-5-yl)spiro[1-azabicyclo[2,2,2]octane-3,5'-oxazolidin]-2'-one, a novel and potent alpha7 nicotinic acetylcholine receptor partial agonist displays cognitive enhancing properties.
Tatsumi R, Fujio M, Takanashi S, Numata A, Katayama J, Satoh H, Shiigi Y, Maeda J, Kuriyama M, Horikawa T, et al. J Med Chem. 2006 Jul 13; 49(14):4374-83.
Discovery of N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide as an agonist of the alpha7 nicotinic acetylcholine receptor: in vitro and in vivo activity. [Bioorg Med Chem Lett. 2008]
Discovery of N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide as an agonist of the alpha7 nicotinic acetylcholine receptor: in vitro and in vivo activity.
Acker BA, Jacobsen EJ, Rogers BN, Wishka DG, Reitz SC, Piotrowski DW, Myers JK, Wolfe ML, Groppi VE, Thornburgh BA, et al. Bioorg Med Chem Lett. 2008 Jun 15; 18(12):3611-5. Epub 2008 May 1.
Review Cognitive improvement by activation of alpha7 nicotinic acetylcholine receptors: from animal models to human pathophysiology. [Curr Pharm Des. 2010]
Review Cognitive improvement by activation of alpha7 nicotinic acetylcholine receptors: from animal models to human pathophysiology.
Thomsen MS, Hansen HH, Timmerman DB, Mikkelsen JD. Curr Pharm Des. 2010 Jan; 16(3):323-43.
Review Selective nicotinic acetylcholine receptor agonists: potential therapies for neuropsychiatric disorders with cognitive dysfunction. [Curr Opin Investig Drugs. 2008]
Review Selective nicotinic acetylcholine receptor agonists: potential therapies for neuropsychiatric disorders with cognitive dysfunction.
Cincotta SL, Yorek MS, Moschak TM, Lewis SR, Rodefer JS. Curr Opin Investig Drugs. 2008 Jan; 9(1):47-56.

See reviews... See all...

Cited by 2 PubMed Central articles

Review Cancer 'survivor-care': I. the α7 nAChR as potential target for chemotherapy-related cognitive impairment. [J Clin Pharm Ther. 2011]
Review Cancer 'survivor-care': I. the α7 nAChR as potential target for chemotherapy-related cognitive impairment.
Raffa RB. J Clin Pharm Ther. 2011 Aug; 36(4):437-45. Epub 2010 Aug 24.
Review Pharmacological enhancement of memory and executive functioning in laboratory animals. [Neuropsychopharmacology. 2011]
Review Pharmacological enhancement of memory and executive functioning in laboratory animals.
Floresco SB, Jentsch JD. Neuropsychopharmacology. 2011 Jan; 36(1):227-50. Epub 2010 Sep 15.

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
BioAssay
PubChem BioAssay experiments on the biological activities of small molecules that cite the current articles. The depositors of BioAssay data provide these references.
Compound (MeSH Keyword)
PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Discovery of 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonan...
Discovery of 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a novel alpha 7 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders in schizophrenia: synthesis, SAR development, and in vivo efficacy in cognition models.
J Med Chem. 2010 Feb 11 ;53(3):1222-37.

PubMed
Bioinspired materials for controlling stem cell fate.
Bioinspired materials for controlling stem cell fate.
Acc Chem Res. 2010 Mar 16 ;43(3):419-28.

PubMed
Postradiation cutaneous vascular tumors of the breast: a review.
Postradiation cutaneous vascular tumors of the breast: a review.
Semin Diagn Pathol. 2009 Aug ;26(3):141-9.

PubMed
Blastocystis hominis--past and future.
Blastocystis hominis--past and future.
Clin Microbiol Rev. 1991 Jan ;4(1):61-79.

PubMed
Eltrombopag for the treatment of chronic immune (idiopathic) thrombocytopenic pu...
Eltrombopag for the treatment of chronic immune (idiopathic) thrombocytopenic purpura.
Oncology (Williston Park). 2009 Nov 30 ;23(13):1171-7.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to:

Discovery of 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a novel alpha 7 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders in schizophrenia: synthesis, SAR development, and in vivo efficacy in cognition models.

Source

Abstract

MeSH Terms, Substances

MeSH Terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Chemical Information

Medical

Supplemental Content

Save items

Related citations in PubMed

Cited by 2 PubMed Central articles

Related information

Recent activity

Simple NCBI Directory

Getting Started

Resources

Popular

Featured

NCBI Information