4-((2-ethoxy-2-oxoethyl)thio)-3-nitrobenzoic acid | 204863-51-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((2-ethoxy-2-oxoethyl)thio)-3-nitrobenzoic acid
• 英文别名: 4-Ethoxycarbonylmethylsulfanyl-3-nitrobenzoic acid；4-(2-ethoxy-2-oxoethyl)sulfanyl-3-nitrobenzoic acid
• CAS: 204863-51-4
• 化学式: C₁₁H₁₁NO₆S
• mdl: MFCD02936794
• 分子量: 285.277
• InChiKey: JFFSVJCOFFOCKB-UHFFFAOYSA-N

物化性质

• 沸点：
  439.1±45.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  135
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P362,P403+P233,P501
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  4-((2-ethoxy-2-oxoethyl)thio)-3-nitrobenzoic acid 在 乙酸酐 、 铁粉 、 溶剂黄146 、 三乙胺 作用下， 反应 17.5h， 生成 (Z)-2-(2,3-difluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxylic acid
  参考文献：
  名称：

  Discovery of a Plasmodium falciparum Glucose-6-phosphate Dehydrogenase 6-phosphogluconolactonase Inhibitor (R,Z)-N-((1-Ethylpyrrolidin-2-yl)methyl)-2-(2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (ML276) That Reduces Parasite Growth in Vitro

  摘要：

  A high-throughput screen of the NIH's MLSMR collection of similar to 340000 compounds was undertaken to identify compounds that inhibit Plasmodium falciparum glucose-6-phosphate dehydrogenase (Pf G6PD). PfG6PD is important for proliferating and propagating P. falciparum and differs structurally and mechanistically from the human orthologue. The reaction catalyzed by glucose-6-phosphate dehydrogenase (G6PD) is the first, rate-limiting step in the pentose phosphate pathway (PPP), a key metabolic pathway sustaining anabolic needs in reductive equivalents and synthetic materials in fast-growing cells. In P. falciparum, the bifunctional enzyme glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase (Pf GluPho) catalyzes the first two steps of the PPP. Because P. falciparum and infected host red blood cells rely on accelerated glucose flux, they depend on the G6PD activity of Pf GluPho. The lead compound identified from this effort, (R,Z)-N-((1-ethylpyrrolidin-2-yl)methyl)-2-(2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carbon-amide, 11 (ML276), is a submicromolar inhibitor of Pf G6PD (IC50 = 889 nM). It is completely selective for the enzyme's human isoform, displays micromolar potency (IC50 = 2.6 mu M) against P. falciparum in culture, and has good drug-like properties, including high solubility and moderate microsomal stability. Studies testing the potential advantage of inhibiting Pf G6PD in vivo are in progress.

  DOI：

  10.1021/jm300833h
• 作为产物：
  描述：

  bis(2-nitro-4-carboxyphenyl) disulfide 在 甲醇 、 sodium sulfide 作用下， 生成 4-((2-ethoxy-2-oxoethyl)thio)-3-nitrobenzoic acid
  参考文献：
  名称：

  US2026629

  摘要：

  公开号：

文献信息

• [EN] AMINE COMPOUNDS<br/>[FR] DERIVES D'INDOLE SERVANT D'ANTAGONISTE DE SOMATOSTATINE
  申请人：TAKEDA CHEMICAL INDUSTRIES LTD

  公开号：WO2004046107A1

  公开（公告）日：2004-06-03

  The present invention provide a compound of the formula (I) wherein ring A represents an aromatic ring optionally having substituents; B, Y and Ya are the same or different and each represents a bond, etc.; R1 and R2 are the same or different and each represents a hydrogen atom, etc.; R3 represents a hydrogen atom, etc.; R4 and R5 are the same or different and each represents a hydrogen, etc.; R6 represents an indolyl group optionally having substituents; and Z and Za are the same or different and each represents a hydrogen atom, etc.; or a salt thereof or a prodrug thereof, having a somatostatin receptor binding inhibition activity and is useful for preventing and/or treating diseases associated with somatostatin.

  本发明提供了一种公式(I)的化合物，其中环A代表一个具有可选取代基的芳香环；B、Y和Ya相同或不同，分别代表一个键等；R1和R2相同或不同，每个代表一个氢原子等；R3代表一个氢原子等；R4和R5相同或不同，每个代表一个氢等；R6代表一个可选有取代基的吲哚基团；Z和Za相同或不同，每个代表一个氢原子等；或其盐或前药，具有生长抑素受体结合抑制活性，并且用于预防或治疗与生长抑素相关的疾病。
• MONOACYLGLYCEROL LIPASE INHIBITORS
  申请人：Stichting Het Nederlands Kanker Instituut- Antoni van Leeuwenhoek Ziekenhuis

  公开号：EP3875452A1

  公开（公告）日：2021-09-08

  Provided are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof: Also provided are compositions comprising compounds of formula (I). The compounds and compositions are also provided for use as medicaments, for example as medicaments useful in the treatment of a condition modulated by monoacylglycerol lipase (MAGL). Also provided are the use of compounds and compositions for the inhibition of monoacylglycerol lipase (MAGL).

  提供的是式(I)的化合物，或其药学上可接受的盐或溶剂： 还提供了包含式(I)化合物的组合物。这些化合物和组合物还可用作药物，例如用于治疗由单酰基甘油脂酶（MAGL）调节的疾病的药物。还提供了利用这些化合物和组合物来抑制单酰基甘油脂酶（MAGL）的用途。
• Quantitative Structure-Activity Relationship Study of N-(3-Oxo-3,4-dihydro-2H-benzo [1,4]thiazine-6-carbonyl)guanidines as Potent Na/H Exchange Inhibitors.
  作者：Takeshi YAMAMOTO、Manabu HORI、Ikuo WATANABE、Kengo HARADA、Shoji IKEDA、Hiroshi OHTAKA

  DOI：10.1248/cpb.48.843

  日期：——

  We have previously reported that N-(4-isopropyl-2, 2-dimethyl-3-oxo-3, 4-dihydro-2H-benzo[1, 4]oxazine-6-carbonyl)guanidine (4b) methanesulfonate salt (KB-R9032) is a potent and highly water-soluble Na/H exchange inhibitor. In a series of studies on Na/H exchange inhibitors, we designed and synthesized N-(3-oxo-3, 4-dihydro-2H-benzo[1, 4]thiazine-6-carbonyl)guanidines (5) as more potent inhibitors with high water-solubility. The design strategy for 5 was based on a quantitative structure-activity relationship (QSAR) study, involving the proportional relationship between the biological activity and hydrophobicity of the ring structure of compounds 4. As expected, compounds 5 showed more potent activity than 4. It was found by using the QSAR analysis that 4 were about five-fold more potent than 4. The increase in potency of compounds 5 well agreed with our previous QSAR analysis result. The most potent derivative was the methanesulfonate salt 5d of the 4-isopropyl derivative(IC50=0.0091μM). And in addition to the in vitro study, 5d showed significant protective activity against a rat acute myocardial infraction model.

  我们以前曾报道过，N-(4-异丙基-2, 2-二甲基-3-氧代-3, 4-二氢-2H-苯并[1, 4]恶嗪-6-甲酰基)胍（4b）甲磺酸盐（KB-R9032）是一种强效、高水溶性的 Na/H 交换抑制剂。在对 Na/H 交换抑制剂的一系列研究中，我们设计并合成了 N-(3-氧代-3,4-二氢-2H-苯并[1,4]噻嗪-6-羰基)胍（5），作为更有效的高水溶性抑制剂。5 的设计策略基于定量结构-活性关系（QSAR）研究，涉及生物活性与化合物 4 环结构疏水性之间的比例关系。通过 QSAR 分析发现，化合物 5 的药效比化合物 4 高出约五倍。最有效的衍生物是 4-异丙基衍生物的甲磺酸盐 5d（IC50=0.0091μM）。除了体外研究外，5d 对大鼠急性心肌梗塞模型也显示出显著的保护活性。
• Indole derivatives as somatostatin agonists or antagonists
  申请人：Abe Hidenori

  公开号：US20060223826A1

  公开（公告）日：2006-10-05

  The present invention provide a compound of the formula (I) wherein ring A represents an aromatic ring optionally having substituents; B, Y and Ya are the same or different and each represents a bond, etc.; R 1 and R 2 are the same or different and each represents a hydrogen atom, etc.; R 3 represents a hydrogen atom, etc.; R 4 and R 5 are the same or different and each represents a hydrogen, etc.; R 6 represents an indolyl group optionally having substituents; and Z and Za are the same or different and each represents a hydrogen atom, etc.; or a salt thereof or a prodrug thereof, having a somatostatin receptor binding inhibition activity and is useful for preventing and/or treating diseases associated with somatostatin.

  本发明提供了一种化合物(I)的公式，其中环A代表一种芳香环，可选地具有取代基; B、Y和Ya相同或不同，每个代表一种键等; R1和R2相同或不同，每个代表一个氢原子等; R3代表一个氢原子等; R4和R5相同或不同，每个代表一个氢等; R6代表一种吲哚基，可选地具有取代基; Z和Za相同或不同，每个代表一个氢原子等; 或其盐或前药，具有生长抑素受体结合抑制活性，并用于预防和/或治疗与生长抑素相关的疾病。
• INDOLE DERIVATIVES AS SOMATOSTATIN AGONISTS OR ANTAGONISTS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1562898A1

  公开（公告）日：2005-08-17