每周分子 | Molecule of the Week

Original ACS 美国化学会 ACS美国化学会 2022-07-01

收录于合集 #每周分子 110个

每周分子：Zoliflodacin

Molecule of the Week: Zoliflodacin

2014年，美国马萨诸塞州威瑟姆市阿斯利康实验室的Gregory S. Basarab及其联合发明人提交了名为“治疗细菌感染的化合物和及其制备方法(Compounds and Methods for Treating Bacterial Infections)”的美国专利申请。本发明的化合物为spiro(isoxazolo[4,5-g][oxazino[4,3-a]quinolinepyrimidine)trione的衍生物。在这些衍生物中，有一种化合物AZD0914，后来被称为zoliflodacin。

本申请的模糊标题掩盖了其特定目的：寻找潜在药物对抗多药耐药性细菌。在本申请的技术背景部分，发明人指出：“根据美国传染病学会报道，美国每年死于耐甲氧西林金黄色葡萄球菌(MRSA)的病人比死于肺气肿、艾滋病毒/艾滋病、帕金森氏症和谋杀的人数加起来还要多。” 他们接着列举了几个当时已经产生抗药性的细菌的例子。

在列出的细菌中有淋病奈瑟菌——一种导致性传播疾病淋病的革兰氏阴性菌。Zoliflodacin是一种DNA旋回酶(细菌拓扑异构酶的一个亚类)抑制剂，对治疗淋病有特别的疗效。今年，John P. Mueller和来自Entasis Therapeutics (AstraZeneca Waltham的子公司)的同事们以及抗菌药物开发专家(Nyack, NY)们共同发表了一份关于zoliflodacin的开发、活性研究、作用模式以及一期和二期临床试验的完整报告。

作者们还宣布了今年将开始对1000名受试者进行临床三期试验。该试验预计将于2021年完成。

Zoliflodacin信息速览

CAS 登记号	1620458-09-4
SciFinder命名	Spiro(isoxazolo [4,5-g][1,4]oxazino [4,3-a]quinoline-5(6H),5′(2′H)-pyrimidine)-2′,4′,6′ (1′H,3′H)-trione, 11-fluoro-1,2,4,4a-tetrahydro-2,4-dimethyl-8-[(4S)-4-methyl-2-oxo-3-oxazolidinyl]-, (2R,4S,4aS)-
分子式	C₂₂H₂₂FN₅O₇
摩尔质量	487.44 g/mol
外观	固体
熔点	未报道
水溶性	0.6 mg/L (est.)

Zoliflodacin危害信息

该物质或其混合物为非危险品

【关于每周分子】

自2001年以来，“每周分子”已成为广受欢迎的栏目。多数分子由读者推荐。每个结构都经由科学家审查，并以3-D和平面图像的形式显示，同时附有该分子简介。可以通过美国化学文摘社 (CAS) 提供的SciFinder中的CAS REGISTRY获取“每周分子”的更多信息。CAS REGISTRY中的每条物质信息都展示了物质的CAS登记号、索引名、通用名、商品名、书目信息等其他更多信息。发送邮件至motw@acs.org推荐您感兴趣的分子吧。

In 2014, Gregory S. Basarab and co-inventors at the AstraZeneca lab in Waltham, MA, filed a US patent application titled “Compounds and Methods for Treating Bacterial Infections”. The compounds of the invention were derivatives of spiro(isoxazolo[4,5-g][oxazino[4,3-a]quinolinepyrimidine)trione. Among the derivatives, there was a compound, AZD0914, that came to be known as zoliflodacin.

The vague title of the application belies its specific purpose: to identify potential drugs to combat multidrug-resistant infectious bacteria. In the background section of the application, the inventors state, “[A]ccording to the Infectious Disease Society of America, methicillin-resistant Staphylococcus aureus (MRSA) kills more Americans every year than emphysema, HIV/AIDS, Parkinson's disease, and homicide combined.” They go on to list several examples of bacteria that had become drug-resistant at the time.

Among the listed bacteria is Neisseria gonorrhoeae, the Gram-negative species that is responsible for the sexually transmitted disease gonorrhea. Zoliflodacin, an inhibitor of DNA gyrase (a subclass of bacterial topoisomerase) is particularly effective for treating this disease. This year, John P. Mueller and co-workers at Entasis Therapeutics (the spinoff from AstraZeneca Waltham) and Antimicrobial Development Specialists (Nyack, NY) published a full report of the development, activity, mode of action, and Phase 1 and 2 clinical trials of zoliflodacin.

The authors also announced the beginning of a Phase 3 trial on ≈1000 subjects this year. The trial is expected to be completed in 2021.

Zoliflodacin azide fast facts

CAS Reg. No.	1620458-09-4
SciFinder nomenclature	Spiro(isoxazolo [4,5-g][1,4]oxazino [4,3-a]quinoline-5(6H),5′(2′H)-pyrimidine)-2′,4′,6′ (1′H,3′H)-trione, 11-fluoro-1,2,4,4a-tetrahydro-2,4-dimethyl-8-[(4S)-4-methyl-2-oxo-3-oxazolidinyl]-, (2R,4S,4aS)-
Empirical formula	C₂₂H₂₂FN₅O₇
Molar mass	487.44 g/mol
Appearance	Solid
Melting Point	Not reported
Water solubility	0.6 g/L (est.)

Zoliflodacin hazard information

Not a hazardous substance or mixture

About Molecule of the Week

MOTW has been a popular feature on ACS website since 2001. Many molecules are suggested by our website visitors. Every structure is reviewed by a scientist and displayed in 3-D and flat images with a brief description. Each week’s molecule also links to a sample record from the CAS REGISTRY, which is searched using SciFinder. Each record displays the registry number, index name and synonyms, bibliographic information, and more. Send us a molecule suggestion at motw@acs.org.

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