Self C R, Barber W E, Machin P J, Osbond J M, Smithen C E, Tong B P, Wickens J C, Bloxham D P, Bradshaw D, Cashin C H
Roche Products Limited, Welwyn Garden City, Herts, England.
J Med Chem. 1991 Feb;34(2):772-7. doi: 10.1021/jm00106a044.
The synthesis of a series of substituted heterocyclic alkoxypropionic acids is described. They were evaluated for antiinflammatory effects in two animal models of chronic inflammation; adjuvant arthritis and type II collagen arthritis in the rat. The desired profile of biological activity was characterized by the reduction of inflammation with the coincident restoration toward normal levels of the biochemical markers (acute phase proteins) associated with the inflammatory response, an effect that was not shared by classical nonsteroidal antiinflammatory agents. Romazarit, (Ro 31-3948, 7), 2-[[2-(4-chlorophenyl)-4-methyl-5-oxazolyl]methoxy]-2-methylpropio nic acid, was selected for further evaluation. In contrast to NSAIDs, romazarit was inactive in animal models of acute inflammation, and furthermore it did not inhibit the cyclooxygenase enzyme in vitro or in vivo. Inhibition of interleukin-1-mediated events in vitro has been observed.
本文描述了一系列取代杂环烷氧基丙酸的合成。在两种慢性炎症动物模型（佐剂性关节炎和大鼠II型胶原性关节炎）中对它们的抗炎作用进行了评估。所需的生物活性特征是炎症减轻，同时与炎症反应相关的生化标志物（急性期蛋白）恢复到正常水平，而经典的非甾体抗炎药没有这种作用。罗美扎利（Ro 31-3948，7），即2-[[2-(4-氯苯基)-4-甲基-5-恶唑基]甲氧基]-2-甲基丙酸，被选作进一步评估。与非甾体抗炎药不同，罗美扎利在急性炎症动物模型中无活性，而且在体外和体内均不抑制环氧化酶。已观察到它在体外可抑制白细胞介素-1介导的反应。
