- Unconventional Synthetic Process of Fasudil Hydrochloride: Costly Homopiperazine Was Avoided
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An efficient, robust, and cost-effective synthetic process of fasudil hydrochloride 1 was developed. Starting from readily available ethylenediamine and 5-isoquinoline sulfonyl chloride, the target product 1 was prepared through a six-step reaction, including sulfonamidation, protection, nucleophilic substitution, deprotection, cyclization, and salification. The process afforded 1 in 67.1% overall yield (based on 5-isoquinoline sulfonyl chloride) with 99.94% purity. Compared to the earlier published methodologies, the use of homopiperazine or its derivatives as intermediates was avoided. The salient features of this environmentally friendly synthetic route include easily available starting materials and operational simplicity, which could be suitable for large-scale industrial production.
- Zhao, Jianhong,Wang, Dingding,Yang, Wu-Lin,Niu, Jinming,Wu, Weiting
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- PRMT5 INHIBITORS AND USES THEREOF
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Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof:wherein Y1 is of formula (?) or formula (y):Ring Y is a 5- to 6-membered heteroaryl ring; and V4, V5, Rx, x, y, and n are as defined herein. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
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Paragraph 00692; 00693
(2016/04/20)
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