Romazarit: a potential disease-modifying antirheumatic drug.

Abstract

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.

• Authors: C R Self, W E Barber, P J Machin, J M Osbond, C E Smithen, B P Tong, J C Wickens, D P Bloxham, D Bradshaw, C H Cashin
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 34 Issue 2 Pg. 772-7 (Feb 1991) ISSN: 0022-2623 [Print] United States
• PMID: 1995900 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Oxazoles
• romazarit

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemical synthesis, therapeutic use)
• Arthritis, Experimental (drug therapy)
• Chemical Phenomena
• Chemistry
• Drug Evaluation, Preclinical
• Female
• Oxazoles (chemical synthesis, therapeutic use)
• Rats
• Structure-Activity Relationship