Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, USA.
J Med Chem. 2010 Feb 11;53(3):1222-37. doi: 10.1021/jm9015075.
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.
一种新型的 alpha 7 nAChR 激动剂，4-(5-甲基恶唑并[4,5-b]吡啶-2-基)-1,4-二氮杂双环[3.2.2]壬烷（24，CP-810,123），已被鉴定为治疗与精神或神经疾病相关的认知障碍的潜在药物，包括精神分裂症和阿尔茨海默病。化合物 24 是一种具有强大和选择性的化合物，具有出色的药物特性。在啮齿动物中，该化合物具有较高的口服生物利用度和优异的脑穿透性，可实现高受体占有率和体内听觉感觉门控和新物体识别的功效。该化合物的结构多样性及其临床前体外和体内资料支持这样一种假设，即 alpha 7 nAChR 激动剂可能具有作为治疗精神分裂症认知障碍的药理学治疗的潜力。
