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

IF 0.6 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

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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

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抗结核的 8-硝基苯并噻嗪酮的多态性和全分子紊乱

8-硝基苯-1,3-噻嗪-4-酮（BTZs）是一类很有前途的抗结核药物，具有新的作用机制，即自杀抑制十烯丙基磷酸基-β- d -核糖2 ' - epimase 1 (DprE1)， DprE1是结核分枝杆菌细胞壁合成的关键酶。8-硝基-2-（胡椒苷-1-基）-6-（三氟甲基）- 4h -苯并-1,3-噻嗪-4-one(1)是抗结核2期临床候选药物BTZ-043的化学简化类似物。利用x射线晶体学对固态中的1进行了结构解析，发现了2种1的多晶形态。1-I在三斜体系（空间群P-1， Z = 6）中结晶，其中一个分子表现出具有优先取向的全分子无序。1-II的晶体结构属于四方体系（空间群P43， Z = 4），在分子的几个部分表现出位置紊乱。x射线结晶学显示抗真菌剂8-硝基-2-（胡椒苷-1-基）-6-（三氟甲基）- 4h -苯并-1,3-噻嗪-4- 1具有三斜（空间群P-1， Z = 6）和四方（空间群P43， Z = 4）多晶型

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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.