methyl 2-(7-hydroxy-4,8-dimethyl-2-oxo-2H-chromen-3-yl)acetate | 433703-81-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: methyl 2-(7-hydroxy-4,8-dimethyl-2-oxo-2H-chromen-3-yl)acetate
• 英文别名: methyl 2-(7-hydroxy-4,8-dimethyl-2-oxochromen-3-yl)acetate
• CAS: 433703-81-2
• 化学式: C₁₄H₁₄O₅
• mdl: MFCD03146921
• 分子量: 262.262
• InChiKey: VHNZFXKDCIJJSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  methyl 2-(7-hydroxy-4,8-dimethyl-2-oxo-2H-chromen-3-yl)acetate 在 sodium hydroxide 作用下， 以 水 、 异丙醇 为溶剂， 以83%的产率得到(7-hydroxy-4,8-dimethyl-2-oxochromen-3-yl)acetic acid
  参考文献：
  名称：

  改性香豆素。25.含有香豆素片段的N-酰基胞嘧啶衍生物

  摘要：

  通过用香豆素-3-乙酸酰化制备新的修饰的胞嘧啶衍生物。

  DOI：

  10.1007/s10600-007-0053-x
• 作为产物：
  描述：

  乙酰丁二酸二甲酯 在 硫酸 作用下， 反应 24.0h， 生成 methyl 2-(7-hydroxy-4,8-dimethyl-2-oxo-2H-chromen-3-yl)acetate
  参考文献：
  名称：

  Substituted 4-methylcoumarin inhibitors of SLC26A3 (DRA) for treatment of constipation and hyperoxaluria

  摘要：

  Substituted 4-methylcoumarins were found to be active against SLC26A3 (DRA) using in vitro and in vivo assays.

  DOI：

  10.1039/d3md00644a

文献信息

• Psoralen derivatives as inhibitors of NF- $$\upkappa \hbox {B/DNA}$$ κ B/DNA interaction: the critical role of the furan ring
  作者：Giovanni Marzaro、Ilaria Lampronti、Monica Borgatti、Paolo Manzini、Roberto Gambari、Adriana Chilin

  DOI：10.1007/s11030-015-9586-2

  日期：2015.8

  Simplified analogues of previously reported NF- $$\upkappa \hbox B/DNA}$$ interaction inhibitors, lacking the furan moiety, were synthesized and evaluated by performing experiments based on electrophoretic mobility shift assay (EMSA). The synthetic modifications led to simpler coumarin derivatives with lower activity allowing to better understand the minimal structural requirement for the binding to NF- $$\upkappa \hbox B}$$ .

  通过基于电泳迁移率测定（EMSA）的实验，合成并评估了以前报道的 NF- $$\upkappa （hbox B/DNA}$$ 相互作用抑制剂的简化类似物，这些类似物缺少呋喃分子。通过合成修饰得到了活性较低的简单香豆素衍生物，从而更好地理解了与 NF- $$\upkappa \hbox B}$ 结合的最低结构要求。
• Design, synthesis and fungicidal evaluation of novel psoralen derivatives containing sulfonohydrazide or acylthiourea moiety
  作者：Jingyue Dong、Kun Li、Zeyu Hong、Lei Chen、Liangfu Tang、Lijun Han、Lai Chen、Zhijin Fan

  DOI：10.1007/s11030-022-10402-y

  日期：——

  To search a novel lead structure for antiphytopathogenic fungus agent, a series of novel psoralen derivatives possessing sulfonohydrazide or acylthiourea structure were designed and synthesized, and their fungicidal activity against seven phytopathogens was evaluated. Their structures were confirmed by melting points, 1H NMR, 13C NMR and HRMS, and the typical crystal structure was determined by X-ray

  为了寻找抗植物病原真菌剂的新型先导结构，设计合成了一系列具有磺酰肼或酰基硫脲结构的新型补骨脂素衍生物，并评价了它们对七种植物病原体的杀真菌活性。它们的结构通过熔点、1 H NMR、13 C NMR和HRMS确定，典型的晶体结构通过X射线衍射确定以进行验证。初步杀真菌活性表明，一些标题化合物表现出一定至高的杀真菌活性。化合物I-13对Botrytis cinerea、Cercospora arachidicola和Physalospora piricola具有良好的杀真菌活性，具有 EC50 个值分别为 12.49、13.22 和 12.12 μg/mL。化合物II-9和II-15在体外显示出 50 μg/mL对B. cinerea的超过 90% 的抑制作用。特别是，II-9表现出显着更高的杀真菌活性，EC 50值为 9.09 μg/mL，低于阳性对照 YZK-C22 (13.41 μg/m
• 2H-chromene and 7H-furo-chromene derivatives selectively inhibit tumour associated human carbonic anhydrase IX and XII isoforms
  作者：Lisa Sequeira、Simona Distinto、Rita Meleddu、Marco Gaspari、Andrea Angeli、Filippo Cottiglia、Daniela Secci、Alessia Onali、Erica Sanna、Fernanda Borges、Eugenio Uriarte、Stefano Alcaro、Claudiu T. Supuran、Elias Maccioni

  DOI：10.1080/14756366.2023.2270183

  日期：2023.12.31

  Tumour associated carbonic anhydrases (CAs) IX and XII have been recognised as potential targets for the treatment of hypoxic tumours. Therefore, considering the high pharmacological potential of t...

  肿瘤相关碳酸酐酶 (CA) IX 和 XII 已被认为是治疗缺氧肿瘤的潜在靶标。因此，考虑到它的高药理潜力...
• WO2019210103A5
  申请人：——

  公开号：WO2019210103A5

  公开（公告）日：2022-05-09
• 4,8-Dimethylcoumarin Inhibitors of Intestinal Anion Exchanger slc26a3 (Downregulated in Adenoma) for Anti-Absorptive Therapy of Constipation
  作者：Sujin Lee、Onur Cil、Peter M. Haggie、Alan S. Verkman

  DOI：10.1021/acs.jmedchem.9b01192

  日期：2019.9.12

  The chloride/bicarbonate exchanger SLC26A3 (downregulated in adenoma) is expressed mainly in colonic epithelium, where it dehydrates the stool by facilitating the final step of chloride and fluid absorption. SLC26A3 inhibition has predicted efficacy in various types of constipation including that associated with cystic fibrosis. We previously identified, by high-throughput screening, 4,8-dimethylcoumarin inhibitors of murine slc26a3 with IC50 down to similar to 150 nM. Here, we synthesized a focused library of forty-three 4,8-dimethylcoumarin analogues. Structure-activity studies revealed the requirement of 4,8-dimethylcoumarin-3-acetic acid for activity. The most potent inhibitors were produced by replacements at C7, including 3-iodo- (4az) and 3-trifluoromethyl- (4be), with IC50 of 40 and 25 nM, respectively. Pharmacokinetics in mice showed predicted therapeutic concentrations of 4az for >72 h following a single 10 mg/kg oral dose. 4az at 10 mg/kg fully normalized stool water content in a loperamide-induced mouse model of constipation. The favorable inhibition potency, selectivity within the SLC26 family, and pharmacological properties of 4az support its further preclinical development.