Chhabria Mahesh T, Suhagia Bhanubhai N, Brahmkshatriya Pathik S, Raval Priyesha M
Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, India.
Arzneimittelforschung. 2011;61(8):452-7. doi: 10.1055/s-0031-1296227.
Hyperlipidemia is considered one of the key factors for cardiovascular diseases. Based on earlier work on a series of 5-alkyl-4-aryl-3-mercapto-(4H)-1,2,4-triazoles, for further lead modification, a series of 4-(substituted)amino-5-substituted-3-mercapto-(4H)-1,2,4-triazoles was designed. Target compounds were synthesized by the well known Hoggarth synthesis of substituted 1,2,4-triazoles. Synthesized compounds were screened for lipid lowering activity using the "Poloxamer 407 induced hyperlipidemia in rats" model at a dose of 100 mg/kg p.o. Compounds were found to alter serum lipid levels significantly. Most of the compounds significantly reduced serum cholesterol and triglyceride levels. Some of the compounds were found to reduce triglycerides and elevate high density lipoprotein (HDL) levels more than the standard drug atorvastatin (CAS 134523-03-8). Compounds with chloro substitution on aryl rings were found more active in reducing serum lipid levels than other substitutions.
高脂血症被认为是心血管疾病的关键因素之一。基于早期对一系列5-烷基-4-芳基-3-巯基-(4H)-1,2,4-三唑的研究工作，为了进一步对先导化合物进行修饰，设计了一系列4-(取代)氨基-5-取代-3-巯基-(4H)-1,2,4-三唑。目标化合物通过众所周知的霍格思合成法合成取代的1,2,4-三唑。使用“泊洛沙姆407诱导大鼠高脂血症”模型，以100mg/kg口服剂量对合成的化合物进行降脂活性筛选。发现这些化合物能显著改变血清脂质水平。大多数化合物能显著降低血清胆固醇和甘油三酯水平。发现一些化合物降低甘油三酯并提高高密度脂蛋白(HDL)水平的作用比标准药物阿托伐他汀(CAS 134523-03-8)更强。发现芳环上有氯取代的化合物在降低血清脂质水平方面比其他取代的化合物更具活性。
