Synthesis and anti-inflammatory properties of 1,2-dialkoxy-4-(3-dimethylaminopropionyl)benzenes and their 5-halogeno derivatives.
A series of new 1,2-dialkoxy-4-(3-dimethylaminopropionyl)benzene hydrochlorides and their 5-halogeno derivatives were synthesized and studied for anti-inflammatory properties. The diethoxy and dipropoxy derivatives were more active than the dimethoxy derivative and previously reported heterocyclic analogues. The introduction of a halogeno substituent at the 5-position of the dimethoxy derivative aromatic ring potentiated the activity. The 5-bromo derivative was more active than 5-chloro and 5-fluoro derivatives. Anti-inflammatory and analgesic effects of the 5-bromo derivative were less pronounced than those of indomethacin but greater than those of lysine acetylsalicylate (LAS). The 5-bromo derivative was more toxic than LAS but possessed similar gastrotoxicity. This compound was significantly less toxic and significantly less gastrotoxic than indomethacin++. Therapeutic indices of the 5-bromo derivative were significantly greater than those of LAS and indomethacin.
Dauksas
V
V
Faculty of Chemistry, Vilnius University, Lithuania.
Gaidelis
P
P
Udrènaitè
E
E
Kuliesius
V
V
Labanauskas
L
L
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001169:Arthritis, Experimental / Q000188:drug therapy; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000150:complications / Q000517:prevention & control; D018409:Foot Injuries; D007213:Indomethacin / Q000494:pharmacology; D007928:Lethal Dose 50; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010538:Peritonitis / Q000188:drug therapy; D011427:Propiophenones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011427:Propiophenones; D008239:Lysine; D001241:Aspirin; C010395:acetylsalicylic acid lysinate; D007213:Indomethacin