N-[(3R)-1-氮杂双环[2.2.2]辛-3-基]呋喃并[2,3-c]吡啶-5-甲酰胺的发现，一种α7烟碱型乙酰胆碱受体激动剂，用于潜在治疗精神分裂症的认知缺陷：合成与构效关系
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.
作者信息
Wishka Donn G, Walker Daniel P, Yates Karen M, Reitz Steven C, Jia Shaojuan, Myers Jason K, Olson Kirk L, Jacobsen E Jon, Wolfe Mark L, Groppi Vincent E, Hanchar Alexander J, Thornburgh Bruce A, Cortes-Burgos Luz A, Wong Erik H F, Staton Brian A, Raub Thomas J, Higdon Nicole R, Wall Theron M, Hurst Raymond S, Walters Rodney R, Hoffmann William E, Hajos Mihaly, Franklin Stanley, Carey Galen, Gold Lisa H, Cook Karen K, Sands Steven B, Zhao Sabrina X, Soglia John R, Kalgutkar Amit S, Arneric Stephen P, Rogers Bruce N
机构信息
Pfizer Global Research & Development, Eastern Point Road, Groton, Connecticut 06340, USA.
出版信息
J Med Chem. 2006 Jul 13;49(14):4425-36. doi: 10.1021/jm0602413.
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 alpha7 neuronal nicotinic acetylcholine receptor (alpha7 nAChR), has been identified as a potential treatment of cognitive deficits in schizophrenia. Compound 14 is a potent and selective alpha7 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.
N-[(3R)-1-氮杂双环[2.2.2]辛-3-基]呋喃并[2,3-c]吡啶-5-甲酰胺（14，PHA-543,613）是α7神经元烟碱型乙酰胆碱受体（α7 nAChR）的新型激动剂，已被确定为治疗精神分裂症认知缺陷的潜在药物。化合物14是一种强效且选择性的α7 nAChR激动剂，具有出色的体外特性。该化合物的特点是在大鼠体内脑内快速渗透且口服生物利用度高，并在听觉感觉门控以及评估认知表现的体内模型——新物体识别中显示出体内疗效。
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