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أ. د. عبدالرحمن بن عبدالعزيز المهيزع Prof. Abdulrahman A. Almehizia

Professor

Professor of Medicinal Chemistry

كلية الصيدلة
كلية الصيدلة (مبنى رقم 23) الدور الثاني مكتب رقم 2 أ 133
publication
Journal Article
2013

Novel triaryl sulfonamide derivatives as selective cannabinoid receptor 2 inverse agonists and osteoclast inhibitors: discovery, optimization, and biological evaluation

P, Yang . 2013

Cannabinoid receptors have gained increasing attention as drug targets for developing potential therapeutic ligands. Here, we report the discovery and optimization of triaryl sulfonamides as a novel series possessing significant CB2 receptor affinity and selectivity. Four sets of triaryl ligands were designed and synthesized for further structural modifications and led to the identification of eight compounds as potent and selective CB2 inverse agonists with high binding affinity (CB2K(i) < 10 nM). Especially, compound 57 exhibited the strongest binding affinity on the CB2 receptor (CB2K(i) of 0.5 nM) and the best selectivity over the CB1 receptor (selectivity index of 2594). Importantly, 57 also showed potent inhibitory activity on osteoclast formation, and it was confirmed by a cell viability assay that the inhibition effects were not derived from the cytotoxicity. Finally, 3D QSAR studies confirmed our SAR findings that three bulky groups play an important role for CB2 receptor binding affinity.

Volume Number
56
Issue Number
5
Magazine \ Newspaper
Journal of Medicinal Chemistry
Pages
2045-58
more of publication
publications

Apurinic/apyrimidinic endonuclease-1/redox effector factor-1 (APE-1) is a critical component of base excision repair that excises abasic lesions created enzymatically by the action of DNA…

by Zhiwei F, Stanton K, Close D, Wang L, Srinivasan A, Almehizia A, Iyer P, Xie XQ, Johnston P, Gold B
2015
publications

Multiple myeloma (MM) is an uncontrolled differentiation of plasma B cells and the deposits in the bone marrow. MM accounts for 10% of blood cancers and nearly more than 22,000 new cases are…

by Almehizia A, Yang P, Wang L, Xie XQ
2013
publications

Cannabinoid receptors have gained increasing attention as drug targets for developing potential therapeutic ligands. Here, we report the discovery and optimization of triaryl sulfonamides as a…

by Yang P, Wang L, Feng R, Almehizia A, Tong Q, Myint KZ, Ouyang Q, Alqarni M, Xie XQ
2013