34259-94-4Relevant articles and documents
ISOTHIAZOLOPYRIMIDINONES, PYRAZOLOPYRIMIDINONES, AND PYRROLOPYRIMIDINONES AS UBIQUITIN-SPECIFIC PROTEASE 7 INHIBITORS
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Paragraph 0525, (2016/09/08)
The disclosure relates to inhibitors of USP7 inhibitors useful in the treatment of cancers, neurodegenerative diseases, immunological disorders, inflammatory disorders, cardiovascular diseases, ischemic diseases, viral infections and diseases, and bacterial infections and diseases, having the Formula: where R1, R2, R3, R4, R5, R5′, X1, X2, X3, n, and m are described herein.
Novel pyridylmethylamines as highly selective 5-HT1A superagonists
Bollinger, Stefan,Hübner, Harald,Heinemann, Frank W.,Meyer, Karsten,Gmeiner, Peter
experimental part, p. 7167 - 7179 (2010/12/19)
To further improve the maximal serotonergic efficacy and better understand the configurational requirements for 5-HT1A binding and activation, we generated and biologically investigated structural variants of the lead structure befiradol. For a bioisosteric replacement of the 3-chloro-4-fluoro moiety, a focused library of 63 compounds by solution phase parallel synthesis was developed. Target binding of our compound collection was investigated, and their affinities for 5-HT2, α1, and α2-adrenergic as well as D1-D4 dopamine receptors were compared. For particularly interesting test compounds, intrinsic activities at 5-HT1A were examined in vitro employing a GTPγS assay. The investigation guided us to highly selective 5HT1A superagonists. The benzothiophene-3-carboxamide 8bt revealed almost exclusive 5HT1A recognition with a Ki value of 2.7 nM and a maximal efficacy of 124%. To get insights into the bioactive conformation of our compound collection, we synthesized conformationally constrained bicyclic scaffolds when SAR data indicated a chair-type geometry and an equatorially dispositioned aminomethyl substituent for the 4,4-disubstituted piperidine moiety.
