Disclosing the Rich Crystal Chemistry of Lesinurad by ab Initio Laboratory X-ray Powder Diffraction Methods

被引:5
作者
Terruzzi, Stephanie [1 ,2 ]
Bellomi, Sonja [3 ]
Marras, Giovanni [3 ]
Barreca, Giuseppe [3 ]
Ventimiglia, Giampiero [3 ]
Cervellino, Antonio [4 ]
Masciocchi, Norberto [1 ,2 ]
机构
[1] Univ Insubria, Dipartimento Sci & Alta Tecnol, Via Valleggio 11, I-22100 Como, Italy
[2] Univ Insubria, To Sca Lab, Via Valleggio 11, I-22100 Como, Italy
[3] Chemessentia Srl, Via Bovio 6, I-28100 Novara, Italy
[4] Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland
关键词
DISCOVERY;
D O I
10.1021/acs.cgd.8b01083
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Lesinurad, a uric acid reabsorption inhibitor that received Food and Drug Administration approval in 2015, is known to crystallize in three unsolvated crystal forms and in a few solvated phases. The structures of the former have been determined by state-of-the-art powder diffraction methods, highlighting significant conformational as well as supramolecular differences, resulting in hydrogen bonded centrosymmetric dimers (Form 1) or helical chains (Form 2). In the complex crystal packing in Form 3, additional one-dimensional (1D) ribbons held together by unexpected C=O center dot center dot center dot Br interactions of the halogen-bond type are found. Thermal analyses and variable-temperature powder diffraction measurements (including high temperature synchrotron X-ray diffraction experiments) provided evidence for the reversible formation of a new phase, Form 2hT, obtained upon heating above 100 degrees C powders of Form 2. Structure solution and refinement of the high-temperature phase made it possible to attribute the structural change to a 60 degrees rotation of the cyclopropyl residue, leaving unaffected the conformation of the (longer) polar branch and the supramolecular 1D helical chain arrangement found in the RT phase.
引用
收藏
页码:6863 / 6872
页数:10
相关论文
共 27 条
[1]   A systematic structural study of halogen bonding versus hydrogen bonding within competitive supramolecular systems [J].
Aakeroey, Christer B. ;
Spartz, Christine L. ;
Dembowski, Sean ;
Dwyre, Savannah ;
Desper, John .
IUCRJ, 2015, 2 :498-510
[2]   Quanto:: a Rietveld program for quantitative phase analysis of polycrystalline mixtures [J].
Altomare, A ;
Burla, MC ;
Giacovazzo, C ;
Guagliardi, A ;
Moliterni, AGG ;
Polidori, G ;
Rizzi, R .
JOURNAL OF APPLIED CRYSTALLOGRAPHY, 2001, 34 :392-397
[3]  
[Anonymous], CHEMSKETCH VERS 2017
[4]   The MYTHEN detector for X-ray powder diffraction experiments at the Swiss Light Source [J].
Bergamaschi, Anna ;
Cervellino, Antonio ;
Dinapoli, Roberto ;
Gozzo, Fabia ;
Henrich, Beat ;
Johnson, Ian ;
Kraft, Philipp ;
Mozzanica, Aldo ;
Schmitt, Bernd ;
Shi, Xintian .
JOURNAL OF SYNCHROTRON RADIATION, 2010, 17 :653-668
[5]   A FUNDAMENTAL PARAMETERS APPROACH TO X-RAY LINE-PROFILE FITTING [J].
CHEARY, RW ;
COELHO, A .
JOURNAL OF APPLIED CRYSTALLOGRAPHY, 1992, 25 (pt 2) :109-121
[6]  
Chen M., Patent, Patent No. [US20160297778, 20160297778]
[7]  
Coelho A. A., 2005, TOPAS R V3 0
[8]  
David W.I. F., 2006, Structure Determination from Powder Diffraction Data
[9]   Recent encounters with atropisomerism in drug discovery [J].
Glunz, Peter W. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2018, 28 (02) :53-60
[10]  
Guagliardi A., 2015, CRC CONCISE ENCY NAN