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吡咯-2-基-苯基亚烯丙基肼甲脒衍生物作为乙酰胆碱酯酶/β-分泌酶1双重抑制剂的设计、合成与评价

Design, synthesis, , and evaluation of pyrrol-2-yl-phenyl allylidene hydrazine carboximidamide derivatives as AChE/BACE 1 dual inhibitors.

作者信息

Sharma Amit, Rudrawar Santosh, Sharma Ankita, Bharate Sandip B, Jadhav Hemant R

机构信息

Pharmaceutical Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus Vidya Vihar Pilani RJ 333031 India

Institute for Glycomics, Griffith University Gold Coast 4222 Australia.

出版信息

RSC Adv. 2024 Aug 23;14(37):26703-26722. doi: 10.1039/d4ra03589e. eCollection 2024 Aug 22.

DOI:10.1039/d4ra03589e
PMID:39184009
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11341970/
Abstract

Alzheimer's disease (AD) manifests as a progressive decline in cognitive function and mental behavior. Targeting two crucial enzymes associated with AD, acetylcholinesterase (AChE) and BACE 1 (Beta-site APP Cleaving Enzyme), in combination, holds promise for therapeutic breakthroughs. In this study, 40 derivatives of pyrrol-2-yl-phenyl allylidene hydrazine carboximidamide were designed based on prior research. These derivatives underwent synthesis and assessment for their inhibitory potential against AChE and BACE 1. ADME predictions indicated favorable physicochemical properties for these compounds. The findings offer novel avenues for exploring the dual inhibition of AChE and BACE 1 as a promising therapeutic strategy for AD.

摘要

阿尔茨海默病（AD）表现为认知功能和精神行为的进行性衰退。联合靶向与AD相关的两种关键酶，即乙酰胆碱酯酶（AChE）和β-分泌酶1（BACE 1，β位点淀粉样前体蛋白裂解酶），有望实现治疗突破。在本研究中，基于先前的研究设计了40种吡咯-2-基-苯基亚苄基肼甲酰胺衍生物。对这些衍生物进行了合成，并评估了它们对AChE和BACE 1的抑制潜力。ADME预测表明这些化合物具有良好的物理化学性质。这些发现为探索联合抑制AChE和BACE 1作为AD一种有前景的治疗策略提供了新途径。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9550/11341970/351c9ae76905/d4ra03589e-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9550/11341970/a4c149c8bf65/d4ra03589e-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9550/11341970/dd9959e5e841/d4ra03589e-f10.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9550/11341970/c413e0797ad1/d4ra03589e-f12.jpg

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