In 2020 EUR J MED CHEM published article about VON-WILLEBRAND-FACTOR; PLATELET ACTIVATION; PREVENTS THROMBOSIS; LACTIC-ACIDOSIS; METFORMIN; RISK; ADHESION; PRODRUG in [Xin, Guang; Ming, Yue; Wei, Zeliang; Li, Shiyi; Zhang, Xiaoyu; Yu, Kui; Li, Youping; Xing, Zhihua; He, Yarong; Chen, Zhen; Niu, Hai; Huang, Wen] Sichuan Univ, West China Hosp, West China Sch Med, Lab Ethnopharmacol, Chengdu, Peoples R China; [Ji, Chengjie] Hosp Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Clin Lab, Chengdu, Sichuan, Peoples R China; [Morris-Natschke, Susan L.; Lee, Kuo-Hsiung] Univ N Carolina, Nat Prod Res Labs, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA; [Zhang, Boli; Zhang, Junhua] Tianjin Univ Tradit Chinese Med, Tianjin, Peoples R China; [Yang, Xijing] Sichuan Univ, West China Hosp, Anim Expt Ctr, West China Sch Med, Chengdu, Sichuan, Peoples R China; [Niu, Hai] Sichuan Univ, Coll Math, Chengdu, Sichuan, Peoples R China in 2020, Cited 46. The Name is Benzoic anhydride. Through research, I have a further understanding and discovery of 93-97-0. Safety of Benzoic anhydride
Platelet thrombosis is the main pathogeny resulting in the low curability of ischemic stroke, a leading cause of mortality and disability worldwide. Metformin, a biguanide derivative that is the first-line oral medicine for type 2 diabetes, alleviates the severity of ischemic stroke in diabetic patients and suppresses platelet activation in experimental animal model. However, the clinical implementation of commercial biguanide analogs for stroke related to platelet thrombosis remains challenging due to its weak potency, poor pharmacokinetic characteristics and possible hypoglycemia. Here, twenty-three biguanide derivatives were designed and synthesized based on the principles of bioisosteres. These derivatives were evaluated for the activity of antiplatelet thrombosis in vivo. We found that N-tri-fluoromethanesulfonyl biguanide derivative, compound b10, uniquely prevented cerebral infarction as well as neuronal function injury, and significantly decrease the mortality rate of ischemic stroke in the middle cerebral artery occlusion mice without significant side effects. We verified that b10 directly inhibited platelets thrombus formation and decreased the compactness of stroke thrombi. Particularly, b10 exhibited good potency to inhibit human platelet activation including platelet aggregation, adhesion, pseudopodia formation, integrin GPIIb/IIIa activation, CD62P expression and clot retraction. Meanwhile, the pharmacokinetics assessment showed that b10 had satisfying pharmacological characteristics including a longer duration and a higher oral absorption ratio than its parent compound. In addition, b10 remarkably ameliorated not only stroke related to platelet thrombosis but also carotid artery thrombus formation. It is concluded that the novel potent antiplatelet thrombotic agent derived from biguanide is a promising candidate for stroke treatment. (C) 2020 Elsevier Masson SAS. All rights reserved.
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Reference:
Isothiazole – Wikipedia,
,Isothiazole – ScienceDirect.com