Montuschi Paolo
Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Largo F. Vito, 1, 00168 Rome, Italy.
Mini Rev Med Chem. 2008 Jun;8(7):647-56. doi: 10.2174/138955708784567395.
Leukotrienes (LTs), including LTB(4) and cysteinyl-LTs (CysLTs) (LTC(4), LTD(4), and LTE(4)), are potent inflammatory lipid mediators which are derived from 5-lipoxygenase activity. CysLTs, which stimulate CysLT(1) and CysLT(2) receptor subtypes, are functionally involved in the pathophysiology of asthma. Selective CysLT(1) receptor antagonists are effective anti-asthmatic drugs. CysLT(1) receptor antagonists have been developed from leukotriene structural analogs, analogs of FPL 55712, a chromone carboxylic acid, and by random screening of corporate compound banks. This review will examine the biosynthesis, metabolism and mechanism of action of leukotrienes, their role in asthma, the therapeutic implications of the leukotriene pathway inhibition for asthma, and the medicinal chemistry strategies that have been exploited in the design of potent and selective CysLT(1) receptor antagonists.
白三烯（LTs），包括白三烯B4（LTB4）和半胱氨酰白三烯（CysLTs）（白三烯C4（LTC4）、白三烯D4（LTD4）和白三烯E4（LTE4）），是由5-脂氧合酶活性产生的强效炎症脂质介质。刺激半胱氨酰白三烯1型（CysLT1）和半胱氨酰白三烯2型（CysLT2）受体亚型的CysLTs在哮喘的病理生理学中发挥作用。选择性CysLT1受体拮抗剂是有效的抗哮喘药物。CysLT1受体拮抗剂是从白三烯结构类似物、色酮羧酸FPL 55712的类似物以及通过对公司化合物库的随机筛选开发而来的。本综述将探讨白三烯的生物合成、代谢和作用机制、它们在哮喘中的作用、白三烯途径抑制对哮喘的治疗意义，以及在设计强效和选择性CysLT1受体拮抗剂中所采用的药物化学策略。
