title: Synthesis and biological evaluation of some novel thieno[2,3-d] pyrimidine derivatives as potential anti-inflammatory and analgesic agents.
abstract: A novel series of thienopyrimidine derivatives bearing various substituents or linked to various heterocyclic moieties through atoms spacers were prepared starting from 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6- carboxamide potassium salt 3. Twelve out of the prepared compounds were selected and evaluated for their antiinflammatory activity using the formalin-induced paw edema and the turpentine oil-induced granuloma pouch bioassays using diclofenac sodium as a reference standard. The ulcerogenic effects and acute toxicity (ALD50) values of these compounds were also determined. In addition, the analgesic activity of the same compounds was evaluated using the rat tail withdrawal technique. The results revealed that compounds 5a, 13, 14b, 15a, 16a and 16b had high anti-inflammatory effect comparable to diclofenac sodium, whereas compounds 5a, 14a, 15a and 16a revealed pronounced analgesic activity that is equal or higher than that of the reference. All of the tested compounds revealed high GI safety profile and were well tolerated by the experimental animals with high safety margin (ALD50 > 3.0g/Kg).
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. soadhawash@yahoo.com.
authors.forename: Alaa A
authors.initials: AA
authors.lastname: El-Tombary
authors.forename: Soad A M
authors.initials: SA
authors.lastname: El-Hawash
authors.forename: Nargues S
authors.initials: NS
authors.lastname: Habib
authors.forename: Raafat
authors.initials: R
authors.lastname: Soliman
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: El-Ashmawy
authors.forename: Omaima G
authors.initials: OG
authors.lastname: Shaaban
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005557:Formaldehyde; D006099:Granuloma / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D015394:Molecular Structure; D010147:Pain Measurement / Q000187:drug effects*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013623:Tail / Q000187:drug effects*; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014425:Turpentine
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011743:Pyrimidines; D013876:Thiophenes; D005557:Formaldehyde; D014425:Turpentine