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Dihydropyridine Neuropeptide Y Y1 Receptor Antagonists 2. Bioisosteric Urea Replacements

Graham S Poindexter, Marc A Bruce, J Guy Breitenbucher, Mendi A Higgins, S-Y Sit, Jeffrey L Romine, Scott W Martin, Sally A Ward, Rachel T McGovern, Wendy Clarke, John Russell, Ildiko Antal-Zimanyi

Bioorg Med Chem. 2004 Jan 15;12(2):507-21.

PMID: 14723969

Abstract:

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).

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP186185035 BMS-193885 BMS-193885 186185-03-5 Price
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