A Prolific Solvate Former, Galunisertib, under the Pressure of Crystal Structure Prediction, Produces Ten Diverse Polymorphs

• DOI: 10.1021/jacs.9b06634
• Publication Date: 2019-08-09T08:03:22Z
• Authors: Rajni M. Bhardwaj; Jennifer A. McMahon; Jonas Nyman; Louise S. Price; Sumit Konar; Iain D. H. Oswald; Colin R. Pulham; Sarah L. Price; Susan M. Reutzel-...
• Keywords: Crystal Structure Prediction; Characterization; Crystal (programming language)

The solid form screening of galunisertib produced many solvates, prompting an extensive investigation into possible risks to the development favored monohydrate form. Inspired by crystal structure prediction, search for neat polymorphs was expanded unusual range experiments, including melt crystallization under pressure, work around solvate formation and thermal instability molecule. Ten were found; however, predicted be most stable has yet obtained. We present structures all ten unsolvated galunisertib, showing how state-of-the-art characterization methods can combined with emerging computational modeling techniques produce a complete landscape assess risk late-appearing, more polymorphs. exceptional conformational polymorphism this prolific former invites further methods, experimental, that are applicable larger, flexible molecules complex landscapes.