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ID: ALA1136537

Journal: Bioorg Med Chem Lett

Title: The discovery of a new class of large-conductance Ca2+-activated K+ channel opener targeted for overactive bladder: synthesis and structure-activity relationships of 2-amino-4-azaindoles.

Authors: Turner SC, Carroll WA, White TK, Gopalakrishnan M, Coghlan MJ, Shieh CC, Zhang XF, Parihar AS, Buckner SA, Milicic I, Sullivan JP.

Abstract: 2-Amino-4-azaindoles have been identified as a structurally novel class of BK(Ca) channel openers. Their synthesis from 2-chloro-3-nitropyridine is described together with their in vitro properties assessed by 86Rb(+) efflux and whole-cell patch-clamp assays using HEK293 cells stably transfected with the BK(Ca) alpha subunit. In vitro functional characterization of BK(Ca) channel opening activity was also assessed by measurement of relaxation of smooth muscle tissue strips obtained from Landrace pig bladders. The preliminary SAR data indicate the importance of steric bulk around the 2-amino substituent.

CiteXplore: 12781183

DOI: 10.1016/s0960-894x(03)00324-x