Bis basic substituted diaminobenzobisthiazoles as potential antiarthritic agents.
A series of benzobisthiazoles were screened for antiinflammatory activity in the carrageenan paw edema and adjuvant arthritis tests. Compound 26, 2,6-bis(N,N-diethylamino)benzo[1,2-d:5,4-d']bisthiazole, was found to inhibit the swelling of the uninjected paw in the prophylactic adjuvant arthritis model with an ED50 of 2.3 mg/kg orally. As with most compounds of this series, 26 was inactive in acute model of inflammation, such as paw edema; like steroids, it showed activity in the granuloma pouch assay but did not inhibit cyclooxygenase, indicating a mode of action different from the classical nonsteroidal antiinflammatory drugs (NSAID's). At doses higher than those producing antiinflammatory activity, 26 had some immunoregulating properties.
Cullen
E
E
Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut 06877.
Becker
R
R
Freter
K
K
LeClerq
T
T
Possanza
G
G
Wong
H C
HC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy; D004487:Edema / Q000188:drug therapy; D006462:Hemolytic Plaque Technique; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D015394:Molecular Structure; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013844:Thiazoles