Synthesis, analgesic and anti-inflammatory activities evaluation of some bi-, tri- and tetracyclic condensed pyrimidines.
Novel series of bicyclic pyrrolo[1,2-c]pyrimidines 3a-g, 5, 6a, b, and 7a, b, tricyclic pyrimido[5,4-e]pyrrolo[1,2-c]pyrimidines 8a-c, 9a-g, 13a-c, 17, 18a, b, 19, 20a,b and 21 and tetracyclic condensed pyrimidines 14, 22 and 23 were synthesized through different chemical reactions. Structures of all synthesized pyrimidine derivatives were supported by spectral and elemental analyses. Analgesic activity evaluation was carried out using acetic acid-induced writhing assay, and all compounds exerted comparable activity to indomethacin. The anti-inflammatory activity evaluation was performed using carrageenan-induced paw edema in rats, the potency of the bicyclic derivatives 3a-f and 7b revealed comparable activity to indomethacin without gastric ulceration. The tricyclic derivatives 13a and 20a exerted good activity, however, they induced gastric ulcers while 13b and 13c showed moderate activity without ulceration. In case of tetracyclic derivatives, compound 14 exhibited the highest potency and safety profile.
Amin
Kamilia M
KM
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, ElKasr Eleini Street, 11562 Cairo, Egypt.
Hanna
Mona M
MM
Abo-Youssef
Hanan E
HE
George
Riham F
RF
D000700:Analgesics / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D018360:Crystallography, X-Ray; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D008958:Models, Molecular; D010147:Pain Measurement / Q000187:drug effects; D011743:Pyrimidines / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D014456:Ulcer / Q000209:etiology
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D011743:Pyrimidines