Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1,3,5-triarylpyrazoline and 1,5-diarylpyrazole derivatives as selective COX-2 inhibitors

Khaled R A Abdellatif; Eman K A Abdelall; Wael A A Fadaly; Gehan M Kamel

doi:10.1016/j.bmcl.2015.11.105

Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1,3,5-triarylpyrazoline and 1,5-diarylpyrazole derivatives as selective COX-2 inhibitors

Bioorg Med Chem Lett. 2016 Jan 15;26(2):406-412. doi: 10.1016/j.bmcl.2015.11.105. Epub 2015 Dec 1.

Authors

Khaled R A Abdellatif¹, Eman K A Abdelall², Wael A A Fadaly², Gehan M Kamel³

Affiliations

¹ Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. Electronic address: khaled.ahmed@pharm.bsu.edu.eg.
² Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
³ Pharmacology Department, Faculty of Veterinary, Cairo University, Cairo, Egypt.

PMID: 26691756
DOI: 10.1016/j.bmcl.2015.11.105

Abstract

Two new series of 1,3,5-triarylpyrazolines 10a-m and 1,5-diarylpyrazoles 14a-d were synthesized. All prepared compounds were evaluated for their in vitro COX-1/COX-2 inhibitory activity and the in vivo anti-inflammatory activity. All compounds were more selective for COX-2 isozyme and showed good in vivo anti-inflammatory activity. Compound 10k was the most COX-2 selective compound (S.I.=5.91) and the most potent anti-inflammatory derivative (ED50=99μmol/kg) which is approximately five folds more potent than ibuprofen (ED50=499μmol/kg) and had half potency of celecoxib (ED50=47μmol/kg). All compounds were less ulcerogenic (Ulcer Indexes=1.20-5.00) than ibuprofen (Ulcer Index=20.25) and comparable to celecoxib (Ulcer Index=2.90).

Keywords: 1,5-Diarylpyrazole; Anti-inflammatory; Cyclooxygenase-2 inhibitors; Pyrazoline.

MeSH terms

Anti-Inflammatory Agents / chemical synthesis
Anti-Inflammatory Agents / chemistry*
Anti-Inflammatory Agents / pharmacology*
Cyclooxygenase 1 / metabolism
Cyclooxygenase 2 / metabolism
Cyclooxygenase 2 Inhibitors / chemical synthesis
Cyclooxygenase 2 Inhibitors / chemistry*
Cyclooxygenase 2 Inhibitors / pharmacology*
Humans
Pyrazoles / chemical synthesis
Pyrazoles / chemistry*
Pyrazoles / pharmacology*
Ulcer / chemically induced

Substances

Anti-Inflammatory Agents
Cyclooxygenase 2 Inhibitors
Pyrazoles
Cyclooxygenase 1
Cyclooxygenase 2