Synthesis and antimuscarinic activity of a series of 4-(1-Imidazolyl)-2,2-diphenylbutyramides: discovery of potent and subtype-selective antimuscarinic agents.

In a study directed toward the development of new, selective agents with potential utility in the treatment of altered smooth muscle contractility and tone, for example, as seen in urinary incontinence associated with bladder muscle instability, a series of 4-(1-imidazolyl)-2,2-diphenylbutyramide derivatives was prepared. These compounds were examined for M1, M2, and M3 muscarinic receptor subtype selectivity in isolated tissue assays. The compounds that showed potency and/or selectivity in these tests were further evaluated for in vivo anticholinergic effects on various organs and tissues, including urinary bladder, salivary gland, and eye in rats. The structure activity relationships for the series of 4-(1-imidazolyl)-2,2-diphenylbutyramide derivatives are also discussed. This study led to the identification of 4-(2-methyl-1-imidazolyl)-2,2-diphenylbutyramide (KRP-197) as a candidate drug for the treatment of urinary bladder dysfunction.

XPS and STM studies of pseudo-AgX monolayers organized on Ag(111) and Au/Ag(111) surfaces.

Simple and well-defined model AgX surfaces are useful to illuminate a variety of surface-related phenomena associated with AgX microcrystals in a different perspective with fewer experimental impediments. From this viewpoint, we discuss a couple of pseudo-AgX monolayers that can be organized on a highly planar sputter-grown Ag(111) or ultrathin-Au-covered Ag(111) film. The monolayer structures have been satisfactorily characterized by combination of XPS and STM methods. In particular, the monolayer AgX formed on Au/Ag(111) proved to have an almost identical structure with the bilayer AgX(111) atomic configuration, thus serving as a superior monolayer model of AgX or pseudo 2D ionic crystal for deeper understanding of the processes involving the AgX surfaces.