Quinolizidinone Carboxylic Acids as CNS Penetrant, Selective M1 Allosteric Muscarinic Receptor Modulators
Quinolizidinone Carboxylic Acids as CNS Penetrant, Selective M1 Allosteric Muscarinic Receptor Modulators
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DOI：
10.1021/ml100095k
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发表时间：
2010-09-01
影响因子：
4.2
通讯作者：
Bilodeau, Mark T.
中科院分区：
文献类型：
--
作者：
Kuduk, Scott D.;Chang, Ronald K.;Bilodeau, Mark T.
M 1毒蕈碱受体的正向变构调节代表了治疗阿尔茨海默病患者认知能力下降的方法。用带有碱性胺键的喹嗪酮取代喹诺酮羧酸系列M1调节剂中的喹诺酮环系统，得到一系列具有较高游离分数、增强的CNS暴露和改善的啮齿动物体内认知模型中的功效的化合物。
Positive allosteric modulation of the M, muscarinic receptor represents an approach to treat the cognitive decline in patients with Alzheimer's disease. Replacement of a quinolone ring system in a quinolone carboxylic acid series of M, modulators with a quinolizidinone bearing a basic amine linkage led to a series of compounds with higher free fraction, enhanced CNS exposure, and improved efficacy in rodent in vivo models of cognition.