methyl 2,4-dichloro-5-sulfamoyl-benzoate | 5046-15-1

• 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: methyl 2,4-dichloro-5-sulfamoyl-benzoate
• 英文别名: Methyl 5-(aminosulfonyl)-2,4-dichlorobenzoate；methyl 2,4-dichloro-5-sulfamoylbenzoate
• CAS: 5046-15-1
• 化学式: C₈H₇Cl₂NO₄S
• mdl: MFCD00099226
• 分子量: 284.12
• InChiKey: ZXSGVNRCYQXHNK-UHFFFAOYSA-N

物化性质

• 熔点：
  202 °C
• 沸点：
  447.9±55.0 °C(Predicted)
• 密度：
  1.576±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  94.8
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2935009090

反应信息

• 作为反应物：
  描述：

  methyl 2,4-dichloro-5-sulfamoyl-benzoate 在 hydrazine hydrate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 2,4-dichloro-5-(carbazoyl)benzenesulfonamide
  参考文献：
  名称：

  Carbonic anhydrase inhibitors. Synthesis of a novel series of 5-substituted 2,4-dichlorobenzenesulfonamides and their inhibition of human cytosolic isozymes I and II and the transmembrane tumor-associated isozymes IX and XII

  摘要：

  A series of novel 5-substituted 2,4-dichlorobenzenesulfonamides 5a-c, 6a-d, 7a-j and 10a-i have been synthesized and investigated as inhibitors of four isoforms of zinc enzyme carbonic anhydrase (CA.EC 4.2.1.1), that is the cytosolic CA I and II, and tumor-associated isozymes CA IX and XII. Against the human CA I investigated compounds displayed K-I values from 349 to 7355 nM, toward hCA II at range of 6.9 to 164 nM, while against hCA IX ranging from 2.8 to 76 nM and against hCA XII in the range of 2.7 to 95 nM. The excellent inhibitory activity against tumor-associated hCA IX was found. The twenty one new compounds displayed a powerful inhibitory potency toward hCA IX (K-I = 2.8-21.7 nM) in comparison with the clinically used CAIs AAZ, MZA, EZA, DCP and IND (24-50 nM). Among them the most potent hCA IX inhibitor 7b (K-I = 2.8 nM) was 8.5-fold stronger than IND (K-I = 24 nM). Toward tumor-associated hCA XII compounds 6c and 10a (K-I = 2.7 and 2.8 nM, respectively) showed a better inhibitory potency than reference sulfonamides MZA and IND (K-I = 3.4 nM). (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.039
• 作为产物：
  描述：

  2,4-二氯-5-磺酰胺基苯甲酸 在 氯化亚砜 作用下， 反应 5.0h， 生成 methyl 2,4-dichloro-5-sulfamoyl-benzoate
  参考文献：
  名称：

  Carbonic anhydrase inhibitors. Synthesis of a novel series of 5-substituted 2,4-dichlorobenzenesulfonamides and their inhibition of human cytosolic isozymes I and II and the transmembrane tumor-associated isozymes IX and XII

  摘要：

  A series of novel 5-substituted 2,4-dichlorobenzenesulfonamides 5a-c, 6a-d, 7a-j and 10a-i have been synthesized and investigated as inhibitors of four isoforms of zinc enzyme carbonic anhydrase (CA.EC 4.2.1.1), that is the cytosolic CA I and II, and tumor-associated isozymes CA IX and XII. Against the human CA I investigated compounds displayed K-I values from 349 to 7355 nM, toward hCA II at range of 6.9 to 164 nM, while against hCA IX ranging from 2.8 to 76 nM and against hCA XII in the range of 2.7 to 95 nM. The excellent inhibitory activity against tumor-associated hCA IX was found. The twenty one new compounds displayed a powerful inhibitory potency toward hCA IX (K-I = 2.8-21.7 nM) in comparison with the clinically used CAIs AAZ, MZA, EZA, DCP and IND (24-50 nM). Among them the most potent hCA IX inhibitor 7b (K-I = 2.8 nM) was 8.5-fold stronger than IND (K-I = 24 nM). Toward tumor-associated hCA XII compounds 6c and 10a (K-I = 2.7 and 2.8 nM, respectively) showed a better inhibitory potency than reference sulfonamides MZA and IND (K-I = 3.4 nM). (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.039

文献信息

• [EN] SELECTIVE INHIBITORS OF CARBONIC ANHYDRASE<br/>[FR] INHIBITEURS SÉLECTIFS D'ANHYDRASE CARBONIQUE
  申请人：UNIV VILNIUS

  公开号：WO2017017505A1

  公开（公告）日：2017-02-02

  Invention is related to novel compounds – benzenesulfonamides of general formulas (I) and (II). The compounds can be used in biomedicine as active ingredients in pharmaceutical formulations, because they inhibit enzymes which participate in disease progression. Acknowledgements: This research was funded by the European Social Fund under the Global Grant measure (no. VP1-3.1.-SMM-07-K-02-009).

  发明涉及新化合物 - 通式（I）和（II）的苯磺酰胺。这些化合物可以作为药物配方中的活性成分在生物医学中使用，因为它们抑制参与疾病进展的酶。致谢：本研究得到欧洲社会基金在全球拨款措施（编号VP1-3.1.-SMM-07-K-02-009）下的资助。
• Methyl 2-Halo-4-Substituted-5-Sulfamoyl-Benzoates as High Affinity and Selective Inhibitors of Carbonic Anhydrase IX
  作者：Audrius Zakšauskas、Edita Čapkauskaitė、Vaida Paketurytė-Latvė、Alexey Smirnov、Janis Leitans、Andris Kazaks、Elviss Dvinskis、Laimonas Stančaitis、Aurelija Mickevičiūtė、Jelena Jachno、Linas Jezepčikas、Vaida Linkuvienė、Andrius Sakalauskas、Elena Manakova、Saulius Gražulis、Jurgita Matulienė、Kaspars Tars、Daumantas Matulis

  DOI：10.3390/ijms23010130

  日期：——

  sulfonamide group, a well-known marker of CA inhibitors, and determined their affinities for all twelve CA isozymes. Variations of substituents on the benzenesulfonamide ring led to compound 4b, which exhibited an extremely high observed binding affinity to CAIX; the Kd was 0.12 nM. The intrinsic dissociation constant, where the binding-linked protonation reactions have been subtracted, reached 0.08 pM. The

  在人体内存在的 12 种具有催化活性的碳酸酐酶同工酶中，CAIX 在各种实体瘤中高度过表达。该酶酸化肿瘤微环境，促进侵袭和转移过程。因此，已经进行了许多尝试来设计化合物，这些化合物相对于其余十一种催化活性CA同工酶表现出高亲和力和选择性结合CAIX，以限制不希望的副作用。据推测，此类药物可能具有抗癌特性，可用于肿瘤治疗。在这里，我们设计了一系列化合物，5-氨磺酰基苯甲酸甲酯，其带有伯磺酰胺基团，这是众所周知的 CA 抑制剂标记，并确定了它们与所有 12 种 CA 同工酶的亲和力。苯磺酰胺环上取代基的变化产生了化合物4b ，它表现出观察到的与 CAIX 极高的结合亲和力； K d为0.12 nM。扣除结合质子化反应后的内在解离常数达到 0.08 pM。该化合物还表现出比其余 C​​A 同工酶高 100 倍的选择性。与 CAIX 结合的化合物3b的 X 射线晶体结构显示了结构位置，而与其他 CA
• 7-MEMBERED RING COMPOUND AND METHOD OF PRODUCTION AND PHARMACEUTICAL APPLICATION THEREOF
  申请人：DAIICHI SANKYO COMPANY, LIMITED

  公开号：US20130296551A1

  公开（公告）日：2013-11-07

  A 7-membered heterocyclic compound having the formula (I), or its salt, or a solvate thereof with a chymase inhibitory action and useful for the prevention or treatment of various diseases, in which chymase is involved: a method for producing the same, and a pharmaceutical composition useful for the prevention or treatment of diseases, in which chymase is involved, including the compound of having the formula (I), or its pharmaceutically acceptable salt, or a solvate thereof are provided.

  提供一种具有式(I)的七元杂环化合物或其盐或其溶剂合物，具有抑制chymase作用，可用于预防或治疗各种与chymase有关的疾病的方法，以及制备该化合物的方法和制备用于预防或治疗与chymase有关的疾病的药物组合物，包括具有式(I)的化合物或其药学上可接受的盐或其溶剂合物。
• Photochemical and Atom-Economical Sulfonylimination of Alkenes with Bifunctional <i>N</i>-Sulfonyl Ketimine
  作者：Lei Wang、Yang Yu、Li Deng、Kang Du

  DOI：10.1021/acs.orglett.3c00724

  日期：——

  tolerance, provides a direct and atom-economic approach for the synthesis of valuable β-amino sulfone derivatives as a single regioisomer. In addition to terminal alkenes, internal alkenes participate in this reaction with high diastereoselectivity. N-Sulfonyl ketimines with aryl or alkyl substituents were found to be compatible with this reaction condition. This method could be applied in the late-stage

  通过使用现成的N-磺酰基酮亚胺作为双功能试剂，开发了烯烃的有机光催化磺酰化。这种转化具有显着的官能团耐受性，为合成有价值的 β-氨基砜衍生物作为单一区域异构体提供了一种直接且原子经济的方法。除了末端烯烃外，内部烯烃也以高非对映选择性参与该反应。发现具有芳基或烷基取代基的N-磺酰基酮亚胺与该反应条件相容。该方法可应用于药物的后期修饰。此外，观察到烯烃正式插入环状磺酰亚胺中，得到扩环产物。
• Selective inhibitors of carbonic anhydrase
  申请人：VILNIUS UNIVERSITY

  公开号：US11312682B2

  公开（公告）日：2022-04-26

  Disclosed are novel compounds—benzenesulfonamides of general formulas (I) and (II) The compounds can be used in biomedicine as active ingredients in pharmaceutical formulations, because they inhibit enzymes which participate in disease progression. Also disclosed are method of treatment using such compounds.

  公开了通式 (I) 和 (II) 的新型化合物-苯磺酰胺 这些化合物可用于生物医学，作为药物制剂的活性成分，因为它们能抑制参与疾病进展的酶。此外，还公开了使用此类化合物进行治疗的方法。