title: Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1-phenylpyrazolo[3,4-d]pyrimidine derivatives.
abstract: A new group of 1-phenylpyrazolo[3,4-d]pyrimidine derivatives 14a-d-21 were synthesized from 2-(6-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)acetohydrazide (12). All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity and ulcerogenic liability. All the target compounds were more potential in inhibiting COX-2 than COX-1. Compounds having pyrazolyl moiety in a hybrid structure with pyrazolo[3,4-d]pyrimidine scaffold (14a-d, 16 and 17) showed higher edema inhibition percentage activities (34-68%) and the 5-aminopyrazole derivative (14c, ED50=87.9 μmol/kg) was the most potent one > celecoxib (ED50=91.9 μmol/kg). While, the in vivo potent compounds (14a-d, 16, 17 and 21) caused variable ulceration effect (ulcer index= 0.33-4.0) comparable to that of celecoxib (ulcer index= 0.33), the pyrazol-3-one derivative (16) and the acetohydrazide (21) were the least ulcerogenic derivatives showing the same ulcerogenic potential of celecoxib.
authors.affiliation: a Department of Pharmaceutical Organic Chemistry , Beni-Suef University , Beni-Suef , Egypt , and.
authors.forename: Rania B
authors.initials: RB
authors.lastname: Bakr
authors.affiliation: b Department of Pharmacology and Toxicology , Beni-Suef University , Beni-Suef , Egypt.
authors.forename: Amany A
authors.initials: AA
authors.lastname: Azouz
authors.affiliation: a Department of Pharmaceutical Organic Chemistry , Beni-Suef University , Beni-Suef , Egypt , and.
authors.forename: Khaled R A
authors.initials: KR
authors.lastname: Abdellatif
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002351:Carrageenan; D000068579:Celecoxib / Q000009:adverse effects; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D015394:Molecular Structure; D011720:Pyrazoles / Q000009:adverse effects* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000009:adverse effects* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced*; D013329:Structure-Activity Relationship
chemical_list: C000614125:1-phenylpyrazolo(3,4-d)pyrimidine; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib
keywords: Anti-inflammatory; cyclooxygenase inhibition; pyrazolo [3,4-d] pyrimidine