2. Academic Validation
  3. Synthesis and biological evaluations of 8-biaryl-2,2-dimethylbenzopyranamide derivatives against Alzheimer's disease and ischemic stroke

Synthesis and biological evaluations of 8-biaryl-2,2-dimethylbenzopyranamide derivatives against Alzheimer's disease and ischemic stroke

  • Bioorg Chem. 2024 Feb:143:107064. doi: 10.1016/j.bioorg.2023.107064.
Ruolin Cao 1,  Fangyu Du 1,  Yuhang Cui 2,  Minggang Qi 1,  Junning Zhuang 1,  Jieru Wang 1,  Maoying Zhang 1,  Xiaoyu Zhang 3,  Zhongbo Liu 3,  Libo Zou 4,  Wei Xiao 5,  Guoliang Chen 6
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 2 Life Science and Biology Pharmacy College, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
  • 3 School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
  • 4 Life Science and Biology Pharmacy College, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: Libozou@163.com.
  • 5 Jiangsu Kanion Pharmaceutical Co., Ltd., Jiangning Industrial City, Economic and Technological Development Zone, Lianyungang, Jiangsu 222001, China. Electronic address: xw_kanion@163.com.
  • 6 Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: chenguoliang@syphu.edu.cn.
PMID: 38150937 DOI: 10.1016/j.bioorg.2023.107064
Abstract

Alzheimer's disease, the commonest cause of dementia, is a growing global health concern with huge implications for individuals and society. Stroke has still been a significant challenge in clinics for a long time, which is the second leading cause of death in the world, especially ischemic stroke. Both Alzheimer's disease and stroke are closely related to oxidative stress and HIF-1 signaling pathways in nerve cells. Herein, we describe our structure-based design, synthesis, and biological evaluation of a new class of 8-biaryl-2,2-dimethylbenzopyranamide derivatives as natural product derivatives. Our efforts have resulted in the discovery of highly potent neuroprotective agents, as exemplified by compound D13 as a HIF-1α Inhibitor, which significant improvement in the behavior of Alzheimer's disease mice and shows great potential improvement of brain infarct volume in pMCAO model rats, improves the increase of blood-brain barrier permeability after cerebral ischemia in rats, neuroprotective effect, reduce the level of apoptotic cells in rats after cerebral ischemia, better than Edaravone.

Keywords

2-dimethylbenzopyranamide derivatives; 8-Biaryl-2; Alzheimer's disease; HIF-1α inhibitor; Stroke.

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