Synthesis and anti-inflammatory testing of some new compounds incorporating 5-aminosalicylic acid (5-ASA) as potential prodrugs.
This work includes the synthesis of 15 final compounds (6a-h and 7b-h) as prodrugs of 5-ASA in the form of the acid itself, esters and amides linked by an amide linkage through a spacer to the endocyclic ring N of nicotinamide. Also, 15 new intermediate compounds were prepared. The target compounds (6b, 6f, 7b, and 7e-h) revealed potent analgesic and anti-inflammatory activities in comparison to sulfasalazine and 5-ASA. In addition, ulcerogenicity, LD50, in vivo and in vitro metabolism of compound 7f were determined.
Abdel-Alim
Abdel-Alim Mohamed
AA
Department of Pharm., Organic Chemistry, Faculty of Pharmacy, University of Assiut, Assiut-71526, Egypt. alim@acc.aun.edu.eg
El-Shorbagi
Abdel-Nasser Ahmed
AN
Abdel-Moty
Samia Galal
SG
Abdel-Allah
Hajjaj Hassan Mohamed
HH
D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D002351:Carrageenan; D004355:Drug Stability; D004487:Edema / Q000517:prevention & control; D005243:Feces / Q000737:chemistry; D005766:Gastrointestinal Contents / Q000382:microbiology; D006863:Hydrogen-Ion Concentration; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D019804:Mesalamine / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D010146:Pain / Q000517:prevention & control; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D012457:Salicylamides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D012459:Salicylates / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D013276:Stomach Ulcer / Q000139:chemically induced; D013297:Streptococcus pyogenes / Q000378:metabolism; D013329:Structure-Activity Relationship
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D012457:Salicylamides; D012459:Salicylates; D019804:Mesalamine; D002351:Carrageenan