Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1376736 | Bioorganic & Medicinal Chemistry Letters | 2006 | 4 Pages |
A series of potent inhibitors of the sodium hydrogen exchanger-1 (NHE-1) is described. Structure–activity relationships identified the 3-methyl-4-fluoro analog 9t as a highly potent (IC50 = 0.0065 μM) and selective (NHE-2/NHE-1 = 1400) non-acylguanidine NHE-1 inhibitor. Pharmacokinetic studies showed that compound 9t has an oral bioavailability of 52% and a plasma half life of 1.5 h in rats. Because of its promising potency, selectivity, and a good pharmacokinetic profile, compound 9t was selected for further studies.
Graphical abstractA series of potent inhibitors of the sodium hydrogen exchanger-1 (NHE-1) is described. Structure–activity relationships identified the 3-methyl-4-fluoro analog 9t as a highly potent (IC50 = 0.0065 μM) and selective (NHE-2/NHE-1 = 1400) non-acylguanidine NHE-1 inhibitor. Pharmacokinetic studies showed that compound 9t has an oral bioavailability of 52% and a plasma half life of 1.5 h in rats.Figure optionsDownload full-size imageDownload as PowerPoint slide