Polymorphism and Whole-Molecule Disorder of an Antitubercular 8-Nitrobenzothiazinone

IF 0.4 4区化学 Q4 CRYSTALLOGRAPHY

Journal of Chemical Crystallography Pub Date : 2024-12-07 DOI:10.1007/s10870-024-01035-0

Rüdiger W. Seidel, Richard Goddard, Tom U. Schlegel, Adrian Richter, Ines Rudolph, Peter Imming

{"title":"Polymorphism and Whole-Molecule Disorder of an Antitubercular 8-Nitrobenzothiazinone","authors":"Rüdiger W. Seidel, Richard Goddard, Tom U. Schlegel, Adrian Richter, Ines Rudolph, Peter Imming","doi":"10.1007/s10870-024-01035-0","DOIUrl":null,"url":null,"abstract":"<div><p>8-Nitrobenzo-1,3-thiazin-4-ones (BTZs) are a promising class of antitubercular agents with a novel mechanism of action, viz. suicide inhibition of decaprenylphosphoryl-β-D-ribose 2’-epimerase 1 (DprE1), an enzyme crucial for cell wall synthesis in the pathogen <i>Mycobacterium tuberculosis</i>. 8-Nitro-2-(piperidin-1-yl)-6-(trifluoromethyl)-4<i>H</i>-benzo-1,3-thiazin-4-one (<b>1</b>) is a chemically simplified analogue of the anti-tuberculosis phase 2 clinical drug candidate BTZ-043. Structural elucidation of <b>1</b> in the solid-state has been carried out by X-ray crystallography and two polymorphic forms of <b>1</b> have been revealed. <b>1</b>-I crystallizes in the triclinic system (space group <i>P</i>-1, <i>Z</i> = 6) with one molecule exhibiting whole-molecule disorder with a preferred orientation. The crystal structure of <b>1</b>-II belongs to the tetragonal system (space group <i>P</i>4<sub>3</sub>, <i>Z</i> = 4) and exhibits positional disorder in several parts of the molecule.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>X-ray crystallography revealed a triclinic (space group <i>P</i>-1, <i>Z</i> = 6) and a tetragonal (space group <i>P</i>4<sub>3</sub>, <i>Z</i> = 4) polymorph of the antimycobacterial agent 8-nitro-2-(piperidin-1-yl)-6-(trifluoromethyl)-4<i>H</i>-benzo-1,3-thiazin-4-one</p></div></div></figure></div></div>","PeriodicalId":615,"journal":{"name":"Journal of Chemical Crystallography","volume":"55 1","pages":"56 - 65"},"PeriodicalIF":0.4000,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10870-024-01035-0.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chemical Crystallography","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s10870-024-01035-0","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CRYSTALLOGRAPHY","Score":null,"Total":0}

引用次数: 0

Abstract

8-Nitrobenzo-1,3-thiazin-4-ones (BTZs) are a promising class of antitubercular agents with a novel mechanism of action, viz. suicide inhibition of decaprenylphosphoryl-β-D-ribose 2’-epimerase 1 (DprE1), an enzyme crucial for cell wall synthesis in the pathogen Mycobacterium tuberculosis. 8-Nitro-2-(piperidin-1-yl)-6-(trifluoromethyl)-4H-benzo-1,3-thiazin-4-one (1) is a chemically simplified analogue of the anti-tuberculosis phase 2 clinical drug candidate BTZ-043. Structural elucidation of 1 in the solid-state has been carried out by X-ray crystallography and two polymorphic forms of 1 have been revealed. 1-I crystallizes in the triclinic system (space group P-1, Z = 6) with one molecule exhibiting whole-molecule disorder with a preferred orientation. The crystal structure of 1-II belongs to the tetragonal system (space group P4₃, Z = 4) and exhibits positional disorder in several parts of the molecule.

Graphical Abstract

X-ray crystallography revealed a triclinic (space group P-1, Z = 6) and a tetragonal (space group P4₃, Z = 4) polymorph of the antimycobacterial agent 8-nitro-2-(piperidin-1-yl)-6-(trifluoromethyl)-4H-benzo-1,3-thiazin-4-one

查看原文本刊更多论文

抗结核的 8-硝基苯并噻嗪酮的多态性和全分子紊乱

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Chemical Crystallography 化学-光谱学

CiteScore

1.50

自引率

12.50%

发文量

审稿时长

6.3 months

期刊介绍： Journal of Chemical Crystallography is an international and interdisciplinary publication dedicated to the rapid dissemination of research results in the general areas of crystallography and spectroscopy. Timely research reports detail topics in crystal chemistry and physics and their relation to problems of molecular structure; structural studies of solids, liquids, gases, and solutions involving spectroscopic, spectrometric, X-ray, and electron and neutron diffraction; and theoretical studies.