Synthesis and antiinflammatory and analgesic properties of 2-amino-1H-benzimidazole and 1,2-dihydro-2-iminocycloheptimidazole derivatives.
2-Amino-1H-benzimidazoles (3) and 1,2-dihydro-2-iminocycloheptimidazoles (4) were synthesized and evaluated for antiinflammatory and analgesic activities. The compounds in the series 3 were synthesized via phenylthioureas (6) or 2-chloro-1H-benzimidazole (12). Most of 4 were synthesized by two methods. One was the reaction of carbodiimides (14) with 2-amino-2,4,6-cycloheptatrien-1-one (method A). The other was the reaction of guanidines (15) with 2-chloro-2,4,6-cycloheptatrien-1-one (method B). Some of the compounds 3 and 4 exhibited potent antiinflammatory and analgesic activities when compared to timegadine (1) or tiaramide hydrochloride (HCl) (17). It was of interest that 1-(2-benzothiazolyl)-2-cyclohexylimino-1,2-dihydrocycloheptimid azole (4e) showed superior analgesic activity to timegadine or tiaramide HCl (ED50 = 1.7 mg/kg p.o. in the acetic acid-induced writhing test, ED30 = 14.0 mg/kg p.o. in Randall-Selitto method) in spite of no effect on prostaglandin E2 synthesis.
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
K
K
Taniguchi
S
S
Shigenaga
T
T
Ogahara
T
T
Fujitsu
M
M
Matsuo
D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D052160:Benzothiazoles; D015232:Dinoprostone / Q000096:biosynthesis; D006146:Guanidines / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001562:Benzimidazoles; D052160:Benzothiazoles; D006146:Guanidines; D007093:Imidazoles; D010879:Piperazines; C028998:timegadine; C003468:tiaramide; D015232:Dinoprostone