N-(3,4-dimethyl-5-isoxazolyl)-2-(carbomethoxy)thiophene-3-sulfonamide | 166962-74-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: N-(3,4-dimethyl-5-isoxazolyl)-2-(carbomethoxy)thiophene-3-sulfonamide
• 英文别名: methyl 3-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]thiophene-2-carboxylate
• CAS: 166962-74-9
• 化学式: C₁₁H₁₂N₂O₅S₂
• 分子量: 316.359
• InChiKey: NOXGIYRKHCVIQI-UHFFFAOYSA-N

物化性质

• 沸点：
  509.3±60.0 °C(predicted)
• 密度：
  1.474±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  135
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(3,4-dimethyl-5-isoxazolyl)-2-(carbomethoxy)thiophene-3-sulfonamide 在 吡啶 、 sodium hydroxide 、 草酰氯 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 为溶剂， 反应 26.0h， 生成 3-[N-(3,4-dimethylisoxazol-5-yl)-N-methoxymethylaminosulfonyl]-2-thiophenecarbonyl chloride
  参考文献：
  名称：

  Endothelin Antagonists:  Substituted Mesitylcarboxamides with High Potency and Selectivity for ET_A Receptors

  摘要：

  We have previously disclosed the discovery of 2,4-disubstituted anilinothiophenesulfonamides with potent ETA-selective endothelin receptor antagonism and the subsequent identification of sitaxsentan (TBC11251, 1) as a clinical development compound (Wu et al. J. Med. Chem. 1997, 40, 1682 and 1690). The orally active 1 has demonstrated efficacy in a phase II clinical trial of congestive heart failure (Givertz ct al. Circulation 1998, 98, Abstr. #3044) and was active in rat models of myocardial infarction (Podesser et al. Circulation. 1998, 98, Abstr. #2896) and acute hypoxia-induced pulmonary hypertension (Chen et al. FASEB J. 1996, 10 (3), A104). We now report that an additional substituent at the 6-position of the anilino ring further increases the potency of this series of compounds. It was also found that a wide range of functionalities at the 3-position of the 2,4,6-trisubstituted ring increased ETA selectivity by similar to 10-fold while maintaining in vitro potency, therefore rendering the compounds amenable to fine-tuning of pharmacological and toxicological profiles with enhanced selectivity. The optimal compound in this series was found to be TBC2576 (7u), which has similar to 10-fold higher ETA binding affinity than 1, high ETA/ETB selectivity, and a serum half-life of 7.3 h in rats, as well as in vivo activity.

  DOI：

  10.1021/jm9900063
• 作为产物：
  描述：

  5-氨基-3,4-二甲基异唑 、 3-氯磺酰基-2-噻吩甲酸甲酯 在 吡啶 、 水 、 二氯甲烷 、 盐酸 、 magnesium sulfate 、 silica gel 、 hexanes ethyl acetate 作用下， 以 吡啶 为溶剂， 反应 16.0h， 以yielded 2.20 mg (65%) of a brown solid的产率得到N-(3,4-dimethyl-5-isoxazolyl)-2-(carbomethoxy)thiophene-3-sulfonamide
  参考文献：
  名称：

  N-Alkyl, N-Alkenyl, N-Alkynyl, N-Aryl and N-fused bicyclo or tricyclo thienyl-, furyl-,and Pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin

  摘要：

  提供了N-烷基，N-烯基，N-炔基，N-芳基和N-融合双环或三环噻吩基，呋喃基和吡咯基磺酰胺以及调节或改变内皮素家族肽活性的方法。具体而言，提供了(苯基)和(苯氧基)噻吩基磺酰胺，(苯基)和(苯氧基)呋喃基磺酰胺以及(苯基)和(苯氧基)吡咯基磺酰胺及其使用方法，通过将磺酰胺与受体接触来抑制内皮素肽与内皮素受体的结合。还提供了通过给予这些磺酰胺或其前药的有效剂量来治疗内皮素介导的疾病的方法，这些磺酰胺或前药能够抑制或增加内皮素的活性。

  公开号：

  US06331637B1

文献信息

• Biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin
  申请人：——

  公开号：US20020095041A1

  公开（公告）日：2002-07-18

  Biphenylsulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, bicyclic or tricyclic carbon or heterocyclic ring biphenylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

  提供了二苯基磺胺类化合物和调节或改变内皮素家族肽活性的方法。具体包括使用双环或三环碳或杂环环二苯基磺胺类化合物的方法，通过将该磺胺类化合物与内皮素受体接触来抑制内皮素肽与内皮素受体的结合。还提供了通过给予有效剂量的这些磺胺类化合物或其前药来治疗内皮素介导的疾病的方法，这些化合物能够抑制或增加内皮素的活性。
• SUBSTITUTED THIOPHENES
  申请人：Gant Thomas G.

  公开号：US20080255036A1

  公开（公告）日：2008-10-16

  Disclosed herein are substituted pyrimidine-based endothelin modulators of Formula I, processes of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

  本文揭示了一种基于嘧啶的Formula I内皮素调节剂的替代物，其制备方法，药物组合物以及使用方法。
• N-aryl thienyl-, furyl-, and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin
  申请人：Texas Biotechnology Corp.

  公开号：US06342610B2

  公开（公告）日：2002-01-29

  Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

  提供了噻吩基、呋喃基和吡咯基磺酰胺以及用于调节或改变内皮素肽家族活性的方法。特别是，提供了N-(异恶唑基)噻吩磺酰胺、N-(异恶唑基)呋喃磺酰胺和N-(异恶唑基)吡咯磺酰胺以及使用这些磺酰胺通过将受体与磺酰胺接触来抑制内皮素肽与内皮素受体结合的方法。还提供了通过施用有效量的一个或多个这些磺酰胺或其前药来治疗内皮素介导的疾病的方法，这些磺酰胺或其前药抑制或增加内皮素的活性。
• Sulfonamides for treatment of endothelin-mediated disorders
  申请人：——

  公开号：US20020091270A1

  公开（公告）日：2002-07-11

  Thienylsulfonamides and their pharmaceutically acceptable derivatives, pharmaceutical compositions, articles of manufacture, combinations, lyophilized powders and methods for the treatment of endothelin diseases using these formulations and sulfonamides are provided. A process of preparing an alkali metal salt of a hydrophobic sulfonamide is provided. The process includes the step of dissolving a free sulfonamide in an organic solvent in the presence of a saturated alkali metal salt solution and recovering the formed sulfonamide salt from the organic phase.

  提供了噻唑磺胺及其药用可接受衍生物、药物组合物、制造物品、组合物、冻干粉剂以及使用这些配方和磺胺类药物治疗内皮素疾病的方法。提供了一种制备疏水性磺胺类化合物的碱金属盐的过程。该过程包括将游离磺胺类化合物溶解在有机溶剂中，在饱和的碱金属盐溶液存在下，并从有机相中回收形成的磺胺类盐的步骤。
• Thienyl-, furyl- and pyrrolyl sulfonamides and derivatives thereof that
  申请人：Texas Biotechnology Corporation

  公开号：US05594021A1

  公开（公告）日：1997-01-14

  Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

  提供了噻吩基、呋喃基和吡咯基磺酰胺以及调节或改变内皮素家族肽活性的方法。具体来说，提供了N-(异噁唑基)噻吩磺酰胺、N-(异噁唑基)呋喃磺酰胺和N-(异噁唑基)吡咯磺酰胺，以及使用这些磺酰胺通过将其与受体接触来抑制内皮素肽与内皮素受体结合的方法。还提供了通过给予这些磺酰胺或其前药的有效量来治疗内皮素介导的疾病的方法，这些磺酰胺或其前药可以抑制或增加内皮素的活性。