3区 · 医学
Article
作者: Clarke, Wendy ; McGovern, Rachel T. ; Sit, S.-Y. ; Russell, John ; Bruce, Marc A. ; Poindexter, Graham S. ; Breitenbucher, J. Guy ; Antal-Zimanyi, Ildiko ; Romine, Jeffrey L. ; Martin, Scott W. ; Ward, Sally A. ; Higgins, Mendi A.
Structure-activity studies around the urea linkage in BMS-193885 (4a) identified the cyanoguanidine moiety as an effective urea replacement in a series of dihydropyridine NPY Y(1) receptor antagonists. In comparison to urea 4a (K(i)=3.3 nM), cyanoguanidine 20 (BMS-205749) displayed similar binding potency at the Y(1) receptor (K(i)=5.1 nM) and full functional antagonism (K(b)=2.6 nM) in SK-N-MC cells. Cyanoguanidine 20 also demonstrated improved permeability properties in Caco-2 cells in comparison to urea 4a (43 vs 19 nm/s).