变构调节
变构调节剂
乙酰胆碱受体
烟碱激动剂
化学
烟碱乙酰胆碱受体
过程(计算)
药理学
受体
计算机科学
生物化学
生物
操作系统
作者
Takayoshi Tajima,Go Ito,Aki Saito,Yoshinori Kohmura
标识
DOI:10.1021/acs.oprd.3c00317
摘要
A practical and efficient process was developed for the manufacture of a positive allosteric modulator (PAM) of the α7 nicotinic acetylcholine receptor via an eight-step synthetic route that furnished a high-quality active pharmaceutical ingredient. Highlights of this synthesis include (1) a highly reproducible palladium-catalyzed cyanation; (2) reduction in the number of steps by revisiting the original protection/deprotection strategy; (3) avoidance of the use of halogenated solvents in all of the steps; (4) replacement of reagents that had procurement issues, such as N-phenyltrifluoromethanesulfonimide and Ghosez's reagent, with more commonly used reagents; and (5) no chromatographic purification in any step. This highly efficient process was successfully demonstrated on a pilot scale to yield up to 63.5 kg of the active pharmaceutical ingredient.
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