title: Design, synthesis and biological screening of some novel celecoxib and etoricoxib analogs with promising COX-2 selectivity, anti-inflammatory activity and gastric safety profile.
abstract: Two new series of 4,6-diaryl-3-cyanopyridine 4a-r and 1,3,5-triaryl-2-pyrazolines 6a-f and were prepared. The new compounds were evaluated for their in vitro COX-2 selectivity and in vivo anti-inflammatory activity. Compounds 4o,r and 6d,f had moderate to high selectivity index (S.I.) compared to celecoxib (selectivity indexes of 4.5, 3.14, 4.79 and 3.21, respectively) and also, showed in vivo anti-inflammatory activity approximately equal to or higher than celecoxib (edema inhibition %=60.5, 64.5, 59.3 and 59.3, after 3h, respectively) and the effective anti-inflammatory doses were (ED50=10.1, 7.8, 8.46 and 10.7mg/kg respectively, celecoxib ED50=10.8mg/kg) and ulcerogenic liability were determined for these compounds which showed promising activity by being more potent than celecoxib with nearly negligible ulcerogenic liability compared to celecoxib (reduction in ulcerogenic liability versus celecoxib=85, 82, 74 and 67%, respectively).
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Fayoum University, Fayoum 63514, Egypt.
authors.forename: Shahinda S R
authors.initials: SS
authors.lastname: Alsayed
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni Suef University, Beni Suef 62514, Egypt.
authors.forename: Heba A H
authors.initials: HA
authors.lastname: Elshemy
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni Suef University, Beni Suef 62514, Egypt; College of Pharmac, Al Jouf University, Sakaka, Al jouf 2014, Saudi Arabia. Electronic address: mohamed.abdelgawad@pharm.bsu.edu.eg.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Abdelgawad
authors.affiliation: Department of Zoology, Faculty of Science, Beni Suef University, Beni Suef 62514, Egypt.
authors.forename: Mahmoud S
authors.initials: MS
authors.lastname: Abdel-Latif
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni Suef University, Beni Suef 62514, Egypt; Pharmaceutical Sciences Department, Ibn Sina National College for Medical Studies, Jeddah 21418, Kingdom of Saudi Arabia.
authors.forename: Khaled R A
authors.initials: KR
authors.lastname: Abdellatif
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D000068579:Celecoxib / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D004487:Edema / Q000188:drug therapy; D000077613:Etoricoxib; D005260:Female; D051379:Mice; D011720:Pyrazoles / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced; D013450:Sulfones / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D013450:Sulfones; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D000077613:Etoricoxib; C020729:3-cyanopyridine
keywords: Anti-inflammatory; Cyanopyridine; Cyclooxygenase inhibition; Pyrazoline