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：比马前列素

Molecule of the Week: Bimatoprost

比马前列素是一款用于治疗和美容(均与眼睛有关)的药物，已经被使用了20年。它与激素的前列腺素家族密切相关。

2001年，美国FDA批准了艾尔建(美国加利福尼亚州欧文)的一款新药申请，该药用于使用比马前列素滴眼剂降低患有开角型青光眼的患者的眼压。7年后，FDA批准了艾尔建将比马前列素用于化妆品的申请：增加睫毛的长度、厚度和暗度。就在去年，FDA批准了艾尔建的缓释比马前列素植入剂的申请，该植入剂可使青光眼患者避免使用眼药水。

比马前列素有几种不良副作用。最常见的一种是结膜炎，它发生在10％以上的患者中。其他还包括视力模糊、虹膜发红、灼热和变暗。当在睫毛上使用该药物时，可能会发生眼睑感染和发黑。

2015年，意大利米兰大学的Diego Romano及其同事报道了一种使用酶促反应改进比马前列素及其表亲拉坦前列素的合成方法。然后，在2019年，比马前列素成为了结合人类知识与机器学习的合成开发项目的“实验对象”。

2012年，蔚山国立科学技术院（韩国）和波兰科学院（华沙）的Bartosz A. Grzybowski发布了Chematica——一种利用化学信息生成合成结果的软件。Grzybowski及其同事更新了Chematica，采取的更新方法为：添加使用该软件数据库的机器学习算法和化学专家的见解，优化其生成的反应结果。

重要的是，hybrid version 的Chematica可以识别很少使用的反应来生成原始版本无法找到的结果。比马前列素合成就是原始Chematica软件被“训练”之前无法呈现的一个例子。

比马前列素信息速览

CAS 登记号	155206-00-1
SciFinder命名	5-Heptenamide, 7-{(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenyl-1-penten-1-yl]cyclopentyl}-N-ethyl-, (5Z)-
分子式	C₂₅H₃₇NO₄
摩尔质量	415.57 g/mol
外观	白色粉末
熔点	67–68 ºC
水溶性	19 mg/L (est.)

比马前列素危害信息

GHS 分类*: 非危害物质或混合物

【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。

Bimatoprost is an almost 20-year-old drug that has medical and cosmetic uses, both pertaining to the eyes. It is closely related to the prostaglandin family of hormones.

In 2001, the US Food and Drug Administration approved a new drug application from Allergan (Irvine, CA) for using bimatoprost eyedrops to lower intraocular pressure in patients suffering from open-angle glaucoma. Seven years later, FDA approved Allergan’s application for a cosmetic use of bimatoprost: increasing the length, thickness, and darkness of eyelashes. Just last year, FDA accepted Allergan’s application for a sustained-release bimatoprost implant that lets glaucoma patients avoid the need for eyedrops.

Bimatoprost has several adverse side effects. The most frequent one is conjunctivitis, which occurs in more than 10% of patients. Others include blurred vision, redness, burning, and darkening of the iris. Eyelid infection and darkening can occur when the drug is used on eyelashes.

In 2015, Diego Romano and co-workers at the University of Milan (Italy) reported an improved synthesis of bimatoprost and its cousin latanoprost that uses enzymatic reactions. Then, in 2019, bimatoprost was a “guinea pig” during the development of a synthesis-planning program that combines human knowledge with machine learning.

In 2012, Bartosz A. Grzybowski of the Ulsan National Institute of Science and Technology (South Korea) and the Polish Academy of Sciences (Warsaw) published Chematica, a program that uses chemical information to generate synthetic sequences. Grzybowski and colleagues updated Chematica by adding machine-learning algorithms that use the software’s database and chemistry experts’ insights to optimize the practicality of the reaction sequences it produces.

Significantly, the hybrid version of Chematica can identify seldom-used reactions to generate sequences that the original version was unable to find. Bimatoprost synthesis is an example of the use of reactions that did not show up before the original Chematica program was “trained”.

Bimatoprost fast facts

CAS Reg. No.	155206-00-1
SciFinder nomenclature	5-Heptenamide, 7-{(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenyl-1-penten-1-yl]cyclopentyl}-N-ethyl-, (5Z)-
Empirical formula	C₂₅H₃₇NO₄
Molar mass	415.57 g/mol
Appearance	White powder
Melting point	67–68 ºC
Water solubility	19 mg/L (est.)

Bimatoprost hazard information

GHS classification*: not a hazardous substance or mixture

*Globally Harmonized System of Classification and Labeling of Chemicals.

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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