Discovery of novel oxazepine and diazepine carboxamides as two new classes of heat shock protein 90 inhibitors. Issue 6 (15th March 2015)

• Record Type: Journal Article
• Authors: Neubert, Timothy; Numa, Mehdi; Ernst, Justin; Clemens, Jeremy; Krenitsky, Paul; Liu, Michael; Fleck, Beth; Woody, Lisa; Zuccola, Harmon; Stamos, Dean
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 6(2015)
• Page Start: 1338
• Page End: 1342
• Publication Date: 2015-03-15
• Subjects: HSP90 inhibitor -- Oaxazepine -- Diazepine -- Macrocycle -- Structure based design; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.01.023
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Two novel series of oxazepine and diazepine based HSP90 inhibitors are reported. This effort relied on structure based design and isothermal calorimetry to identify small drug like macrocycles. Computational modelling was used to build into a solvent exposed pocket near the opening of the ATP binding site, which led to potent inhibitors of HSP90 (25 –30 ).