(E)-4-(3-(3-methoxyphenyl)-3-oxoprop-1-en-1-yl)benzoic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-4-(3-(3-methoxyphenyl)-3-oxoprop-1-en-1-yl)benzoic acid
• 英文别名: 4-[(E)-3-(3-methoxyphenyl)-3-oxoprop-1-enyl]benzoic acid
• 化学式: C₁₇H₁₄O₄
• 分子量: 282.296
• InChiKey: SJDQYBNZACZDGI-JXMROGBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-4-(3-(3-methoxyphenyl)-3-oxoprop-1-en-1-yl)benzoic acid 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 (E)-N-(5-(3,4-dihydroxyphenyl)-1,3,4-thiadiazol-2-yl)-4-(3-(3-methoxyphenyl)-3-oxoprop-1-en-1-yl)benzamide
  参考文献：
  名称：

  Novel 1,3,4-thiadiazole–chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies

  摘要：

  含有邻二酚基团和查尔酮结构的1,3,4-噻二唑化合物被合成并进行抗氧化活性、细胞毒性和DNA结合活性的检查。

  DOI：

  10.1039/c8md00316e
• 作为产物：
  描述：

  对醛基苯甲酸 、 3-甲氧基苯乙酮 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 2.5h， 生成 (E)-4-(3-(3-methoxyphenyl)-3-oxoprop-1-en-1-yl)benzoic acid
  参考文献：
  名称：

  Novel 1,3,4-thiadiazole–chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies

  摘要：

  含有邻二酚基团和查尔酮结构的1,3,4-噻二唑化合物被合成并进行抗氧化活性、细胞毒性和DNA结合活性的检查。

  DOI：

  10.1039/c8md00316e

文献信息

• A chalcone derivative binds a putative allosteric site of YopH: Inhibition of a virulence factor of Yersinia
  作者：Ana C.A. de Souza、Mattia Mori、Larissa Sens、Ruth F. Rocha、Tiago Tizziani、Luiz F.S. de Souza、Louise Domeneghini Chiaradia-Delatorre、Maurizio Botta、Ricardo J. Nunes、Hernán Terenzi、Angela C.O. Menegatti

  DOI：10.1016/j.bmcl.2020.127350

  日期：2020.8

  Identification of allosteric inhibitors of PTPs has attracted great interest as a new strategy to overcome the challenge of discover potent and selective molecules for therapeutic intervention. YopH is a virulence factor of the genus Yersinia , validated as an antimicrobial target. The finding of a second substrate binding site in YopH has revealed a putative allosteric site that could be further exploited. Novel chalcone compounds that inhibit PTPs activity were designed and synthesized. Compound 3j was the most potent inhibitor, interestingly, with different mechanisms of inhibition for the panel of enzymes evaluated. Further, our results showed that com- pound 3j is an irreversible non-competitive inhibitor of YopH that binds to a site different than the catalytic site, but close to the well-known second binding site of YopH.
• Structure Guided Lead Generation for <i>M. tuberculosis</i> Thymidylate Kinase (Mtb TMK): Discovery of 3-Cyanopyridone and 1,6-Naphthyridin-2-one as Potent Inhibitors
  作者：Maruti Naik、Anandkumar Raichurkar、Balachandra S. Bandodkar、Begur V. Varun、Shantika Bhat、Rajesh Kalkhambkar、Kannan Murugan、Rani Menon、Jyothi Bhat、Beena Paul、Harini Iyer、Syeed Hussein、Julie A. Tucker、Martin Vogtherr、Kevin J. Embrey、Helen McMiken、Swati Prasad、Adrian Gill、Bheemarao G. Ugarkar、Janani Venkatraman、Jon Read、Manoranjan Panda

  DOI：10.1021/jm5012947

  日期：2015.1.22

  M. tuberculosis thymidylate kinase (Mtb TMK) has been shown in vitro to be an essential enzyme in DNA synthesis. In order to identify novel leads for Mtb TMK, we performed a high throughput biochemical screen and an NMR based fragment screen through which we discovered two novel classes of inhibitors, 3-cyanopyridones and 1,6-naphthyridin-2-ones, respectively. We describe three cyanopyridone subseries that arose during our hit to lead campaign, along with cocrystal structures of representatives with Mtb TMK. Structure aided optimization of the cyanopyridones led to single digit nanomolar inhibitors of Mtb TMK. Fragment based lead generation, augmented by crystal structures and the SAR from the cyanopyridones, enabled us to drive the potency of our 1,6-naphthyridin-2-one fragment hit from 500 mu M to 200 nM while simultaneously improving the ligand efficiency. Cyanopyridone derivatives containing sulfoxides and sulfones showed cellular activity against M. tuberculosis. To the best of our knowledge, these compounds are the first reports of non-thymidine-like inhibitors of Mtb TMK.
• Synthesis and structure-activity relationship of new chalcone linked 5-phenyl-3-isoxazolecarboxylic acid methyl esters potentially active against drug resistant Mycobacterium tuberculosis
  作者：Santosh Kumar Sahoo、Bandela Rani、Nikhil Baliram Gaikwad、Mohammad Naiyaz Ahmad、Grace Kaul、Manjulika Shukla、Srinivas Nanduri、Arunava Dasgupta、Sidharth Chopra、Venkata Madhavi Yaddanapudi

  DOI：10.1016/j.ejmech.2021.113580

  日期：2021.10

  agents active against emerging drug-resistant Mycobacterium tuberculosis and to counter the long treatment protocol of existing drugs, herein we present synthesis and biological evaluation of a new series of 5-phenyl-3-isoxazolecarboxylic acid methyl ester-chalcone hybrids. Among 35 synthesized compounds, 32 analogues displayed potent in-vitro activity against Mycobacterium tuberculosis H37Rv with MIC

  为了寻找对新出现的耐药结核分枝杆菌有效的新型治疗剂并应对现有药物的长期治疗方案，我们在此介绍了一系列新的 5-苯基-3-异恶唑羧酸甲酯-查耳酮杂化物的合成和生物学评价. 在 35 种合成化合物中，32 种类似物显示出对结核分枝杆菌H37Rv 的有效体外活性，MIC 为 0.12–16 μg/mL。针对 Vero 细胞的细胞活力测试表明 29 种化合物无细胞毒性（CC 50  > 20 μg/mL & SI > 10）。大多数 MIC 为 0.12 μg/mL（7 b、7j、7 ab）的有效化合物的选择性指数 (SI) 超过 320。 进一步研究抗药性结核分枝杆菌显示 7j 是最有效的化合物，MIC 为 0.03–0.5 μg/mL。时间杀伤动力学研究表明，化合物 7j 显示出浓度依赖性杀菌活性，其效力与目前的一线抗结核药物相当。综上所述，7j 呈现出一种新的热门产品，有可能被转化为一种有效的抗分枝杆菌。
• Novel 1,3,4-thiadiazole–chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies
  作者：Katarina Jakovljević、Milan D. Joksović、Ivana Z. Matić、Nina Petrović、Tatjana Stanojković、Dušan Sladić、Miroslava Vujčić、Barbara Janović、Ljubinka Joksović、Snežana Trifunović、Violeta Marković

  DOI：10.1039/c8md00316e

  日期：——

  1,3,4-Thiadiazole compounds containing catechol moiety and chalcone motif are synthesized and examined for antioxidant activity, cytotoxicity and DNA-binding activity.

  含有邻二酚基团和查尔酮结构的1,3,4-噻二唑化合物被合成并进行抗氧化活性、细胞毒性和DNA结合活性的检查。