133141-61-4Relevant academic research and scientific papers
Prospective Identification of Biologically Active Structures by Topomer Shape Similarity Searching
Cramer, Richard D.,Poss, Michael A.,Hermsmeier, Mark A.,Caulfield, Thomas J.,Kowala, Mark C.,Valentine, Maria T.
, p. 3931 - 3933 (2007/10/03)
The principle of bioisosterism - similarly shaped molecules are more likely to share biological properties than are other molecules - has long helped to guide drug discovery. An algorithmic implementation of this principle, based on shape comparisons of a single rule-generated "topomer" conformation per molecule, had been found to be the descriptor most consistently predictive of similar biological properties in retrospective studies, and also to be well-suited for searching large (>10E12) "virtual libraries" of potential reaction products. Therefore a prospective trial of this shape similarity searching method was carried out, with synthesis of 425 compounds and testing of them for inhibition of binding of angiotensin II (A-II). The 63 compounds that were identified by shape searching as most similar to any of four query structures included all of the seven compounds found to be highly active, with none of the other 365 structures being highly active (p0.001). Additional consistent relations (p0.05) were found, among all 425 compounds, between the degree of shape similarity to the nearest query structure and the frequency of various levels of observed activity. Known "SAR" (rules specifying structural features required for A-II antagonism) were also regenerated within the biological data for the 63 shape similar structures.
Benzimidazoles and medicaments containing these compounds
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, (2008/06/13)
The invention relates to benzimidazoles of the formula STR1 in which R1 to R2 are as defined in claim 1, 1 and 3 isomer mixtures thereof and addition salts thereof which have valuable properties. In particular, the novel compounds ar
New nonpeptide angiotensin II receptor antagonists. 1. Synthesis, biological properties, and structure-activity relationships of 2-alkyl benzimidazole derivatives
Thomas,Allott,Gibson,Major,Masek,Oldham,Ratcliffe,Roberts,Russell,Thomason
, p. 877 - 885 (2007/10/02)
On the basis of an extension of the literature lead 1, a series of benzimidazoles have been synthesized and shown to be angiotensin II (AII) receptor antagonists. The structure-activity relationships of these new antagonists have been explored and the key
