Substituted 3-phenyl-7H-thiazolo(3,2-b)(1,2,4)triazin-7-ones as antiinflammatory agents with immunomodulating properties.
After structure-activity relationship studies (SAR) on a novel class of substituted thiazolo(3,2-b)(1,2,4)triazin-7-ones, HWA-131 (3-(3,5-di-tert.butyl-4-hydroxyphenyl)-7H-thiazolo(3,2-b)(1,2,4)triaz in-7-one) was selected for incremental pharmacological investigations. This compound was effective in not only preventing, but also curing established arthritic disorders of rats such as adjuvant and type II collagen arthritis as well as those of mice such as chronic graft-versus-host (CGVH) disease, a model for systemic lupus erythematosus (SLE). Further, this non-immunosuppressive drug effectively inhibited the carrageenan-induced paw oedema, attenuated the active Arthus reaction, and demonstrated antierythema as well as antipyretic activity. Part of the antiinflammatory effects of this new compound is most probably related to its antioxidative activity, as well as inhibition of lipoxygenase metabolites. HWA-131's good gastric tolerance may have to do with its limited ability to inhibit the production of cyclooxygenase metabolites. Based on our data, we are sure that HWA-131 will be an effective nonsteroidal antiinflammatory agent, with immunomodulating properties, to combat human autoimmune disorders.
Bartlett
R R
RR
Department of Pharmacological Research, Hoechst AG Werk Kalle-Albert, Wiesbaden, FRG.
Gebert
U
U
Kerékjártó
B
B
Schleyerbach
R
R
Thorwart
W
W
Weithmann
K U
KU
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology; D001183:Arthus Reaction / Q000188:drug therapy; D015551:Autoimmunity / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000009:adverse effects / Q000494:pharmacology*; D014227:Triazines / Q000009:adverse effects / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013844:Thiazoles; D014227:Triazines; C063617:HWA 131