Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an agonist of the α7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia:: Synthesis and structure-activity relationship

被引：178

作者：

Wishka, Donn G. ^{[1
]}

Walker, Daniel P. ^{[1
]}

Yates, Karen M. ^{[1
]}

Reitz, Steven C. ^{[1
]}

Jia, Shaojuan ^{[1
]}

Myers, Jason K. ^{[1
]}

Olson, Kirk L. ^{[1
]}

Jacobsen, E. Jon ^{[1
]}

Wolfe, Mark L. ^{[1
]}

Groppi, Vincent E. ^{[1
]}

Hanchar, Alexander J. ^{[1
]}

Thornburgh, Bruce A. ^{[1
]}

Cortes-Burgos, Luz A. ^{[1
]}

Wong, Erik H. F. ^{[1
]}

Staton, Brian A. ^{[1
]}

Raub, Thomas J. ^{[1
]}

Higdon, Nicole R. ^{[1
]}

Wall, Theron M. ^{[1
]}

Hurst, Raymond S. ^{[1
]}

Walters, Rodney R. ^{[1
]}

Hoffmann, William E. ^{[1
]}

Hajos, Mihaly ^{[1
]}

Franklin, Stanley ^{[1
]}

Carey, Galen ^{[1
]}

Gold, Lisa H. ^{[1
]}

Cook, Karen K. ^{[1
]}

Sands, Steven B. ^{[1
]}

Zhao, Sabrina X. ^{[1
]}

Soglia, John R. ^{[1
]}

Kalgutkar, Amit S. ^{[1
]}

Arneric, Stephen P. ^{[1
]}

Rogers, Bruce N. ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Groton, CT 06340 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 14期

关键词：

D O I：

10.1021/jm0602413

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

N-[(3R)-1-Azabicyclo[2.2.2] oct-3-yl] furo[2,3-c]pyridine-5-carboxamide (14, PHA-543,613), a novel agonist of the alpha 7 neuronal nicotinic acetylcholine receptor (alpha 7 nAChR), has been identified as a potential treatment of cognitive deficits in schizophrenia. Compound 14 is a potent and selective alpha 7 nAChR agonist with an excellent in vitro profile. The compound is characterized by rapid brain penetration and high oral bioavailability in rat and demonstrates in vivo efficacy in auditory sensory gating and, in an in vivo model to assess cognitive performance, novel object recognition.

引用

页码：4425 / 4436

页数：12

共 65 条

[51]

Schmitt JD, 2000, CURR MED CHEM, V7, P749

[52]

SEGUELA P, 1993, J NEUROSCI, V13, P596

[53] Furopyridines .21. Synthesis of cyano derivatives of furo[2,3-b]-, -[2,3-c]- and -[3,2-c]pyridine and their conversion to derivatives having another carbon-substituent [J].