Chittiboyina Amar G, Venkatraman Meenakshi S, Mizuno Cassia S, Desai Prashant V, Patny Akshay, Benson Stephen C, Ho Christopher I, Kurtz Theodore W, Pershadsingh Harrihar A, Avery Mitchell A
Laboratory for Applied Drug Design and Synthesis, Department of Medicinal Chemistry, School of Pharmacy, University of Mississippi, 38677, USA.
J Med Chem. 2006 Jul 13;49(14):4072-84. doi: 10.1021/jm0510880.
A series of novel derivatives of potent antioxidant vitamin, alpha-lipoic acid, and related analogues were designed, synthesized, and evaluated for their PPARgamma agonist activities. Compounds 9a and the water soluble analogue11e were found to be potent PPARgamma agonists. Compound 9a appeared to have a significant role in improving insulin sensitivity and reducing triglyceride levels in fa/fa rats as well as inhibited proliferation of a variety of normal and neoplastic cultured human cell types. These novel compounds may prove efficacious not only in the treatment of Type 2 diabetes, but also atherosclerosis, prevention of vascular restenosis, and inflammatory skin diseases.
设计、合成了一系列强效抗氧化剂维生素α-硫辛酸的新型衍生物及其相关类似物，并对其过氧化物酶体增殖物激活受体γ（PPARγ）激动剂活性进行了评估。发现化合物9a和水溶性类似物11e是强效PPARγ激动剂。化合物9a似乎在改善fa/fa大鼠的胰岛素敏感性和降低甘油三酯水平方面具有重要作用，并且还能抑制多种正常和肿瘤来源的人培养细胞类型的增殖。这些新型化合物可能不仅在治疗2型糖尿病方面有效，而且在治疗动脉粥样硬化、预防血管再狭窄和炎症性皮肤病方面也有效。
