کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1378916 | 982014 | 2005 | 7 صفحه PDF | دانلود رایگان |

We have reported on the design, synthesis, and biological characterization of (R)-4-[3,4-dioxo-2-(1,2,2-trimethyl-propylamino)-cyclobut-1-enylamino]-3-ethyl-benzonitrile (1),1 a novel, potent, and selective adenosine 5′-triphosphate-sensitive potassium (KATP) channel opener with potential utility for the treatment of urge urinary incontinence (UUI). Excising the aniline-derived nitrogen atom of 1 or replacing it with an aralkyl group, led to bladder smooth muscle relaxant chemotypes 3 and 4, respectively. Prototype compounds in these series were found to produce significant increases in an iberiotoxin (IbTx)-sensitive hyperpolarizing current, thus suggesting that these relatively modest structural modifications resulted in a switch in the mechanism of action of these smooth muscle relaxants from KATP channel openers to activators of the large-conductance Ca2+-activated potassium channel (BKCa). We report herein the syntheses and biological evaluation of a series of substituted 3-amino-4-aryl-(and aralkyl-)cyclobut-3-ene-1,2-diones.
The synthesis and smooth muscle relaxant SAR of a series of novel phenyl- and benzyl-cyclobutenediones are reported.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 15, Issue 10, 16 May 2005, Pages 2495–2501