title: Synthesis and biological evaluation of thieno [2',3':4,5]pyrimido[1,2-b][1,2,4]triazines and thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidines as anti-inflammatory and analgesic agents.
abstract: A new series of thieno[2',3':4,5]pyrimido[1,2-b][1,2,4]triazines and thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidines was synthesized. The newly synthesized compounds were evaluated for their anti-inflammatory and analgesic activity using diclofenac Na as a reference standard. Additionally, the ulcerogenic effects and acute toxicity (ALD50) values of the active compounds were also determined. In general, the thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidine derivatives exhibited better biological activities than the thieno[2',3':4,5]pyrimido[1,2-b][1,2,4]triazines. Collectively, the thienotriazolopyrimidine derivatives 9, 13 and 14a were proved to display distinctive anti-inflammatory activity at the acute and subacute models as well as good analgesic profile with a delayed onset of action. Moreover, they revealed good gastrointestinal safety profile and are well tolerated by experimental animals with high safety margin (ALD50 > 0.3 g/kg).
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt. hayamashour@ymail.com
authors: Hayam M
authors: HM
authors: Ashour
authors: Omaima G
authors: OG
authors: Shaaban
authors: Ola H
authors: OH
authors: Rizk
authors: Ibrahim M
authors: IM
authors: El-Ashmawy
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005557:Formaldehyde; D008297:Male; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011743:Pyrimidines; D013876:Thiophenes; D014227:Triazines; D014230:Triazoles; D005557:Formaldehyde