Romazarit: a potential disease-modifying antirheumatic drug.
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.
Self
C R
CR
Roche Products Limited, Welwyn Garden City, Herts, England.
Barber
W E
WE
Machin
P J
PJ
Osbond
J M
JM
Smithen
C E
CE
Tong
B P
BP
Wickens
J C
JC
Bloxham
D P
DP
Bradshaw
D
D
Cashin
C H
CH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D055598:Chemical Phenomena; D002621:Chemistry; D004353:Drug Evaluation, Preclinical; D005260:Female; D010080:Oxazoles / Q000138:chemical synthesis / Q000627:therapeutic use*; D051381:Rats; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010080:Oxazoles; C063528:romazarit