3-aminomesitoic acid | 106567-40-2

• 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: 3-aminomesitoic acid
• 英文别名: 3-amino-2,4,6-trimethyl-benzoic acid；3-Amino-2,4,6-trimethyl-benzoesaeure；3-Amino-2,4,6-trimethylbenzoic acid
• CAS: 106567-40-2
• 化学式: C₁₀H₁₃NO₂
• 分子量: 179.219
• InChiKey: RGRYYPYFFJPMIO-UHFFFAOYSA-N

物化性质

• 沸点：
  362.4±30.0 °C(Predicted)
• 密度：
  1.170±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：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-aminomesitoic acid 生成 3-amino-2,4,6-trimethylbenzoyl chloride
  参考文献：
  名称：

  Cuyegkeng, Maria Assunta; Mannschreck, Albrecht, Chemische Berichte, 1987, vol. 120, p. 803 - 810

  摘要：

  DOI：
• 作为产物：
  描述：

  2,4,6-三甲基苯甲酸 在 硫酸 、 硝酸 、 氯化铵 、 溶剂黄146 、 锌 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 3-aminomesitoic acid
  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

文献信息

• [EN] SULFONAMIDES AND DERIVATIVES THEREOF THAT MODULATE THE ACTIVITY OF ENDOTHELIN<br/>[FR] SULFONAMIDES ET DERIVES DE CEUX-CI, MODULANT L'ACTIVITE DE L'ENDOTHELINE
  申请人：TEXAS BIOTECHNOLOGY CORPORATION

  公开号：WO1998013366A1

  公开（公告）日：1998-04-02

  (EN) Thienyl-, furyl- and pyrrolyl-sulfonamides, formulations of pharmaceutically acceptable salts thereof 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, formulations thereof 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 the activity of the endothelin are also provided.(FR) L'invention concerne des thiényl-, furyl- et pyrrolyl-sulfonamides, des formulations de sels pharmaceutiquement acceptables de ceux-ci et des procédés de modulation ou de modification de peptides de la famille de l'endothéline. Elle porte notamment sur des N-(isoxazolyl)thiénylsulfonamides, des N-(isoxazolyl)furylsulfonamides et des N-(isoxazolyl)pyrrolylsulfonamides, des formulations de ceux-ci et des procédés dans lesquels ces sulfonamides sont utilisés pour l'inhibition de la liaison d'un peptide d'endothéline à un récepteur de l'endothéline par la mise en contact du récepteur avec le sulfonamide. Elle se rapporte encore à des procédés de traitement de troubles dont l'endothéline est à l'origine, qui consistent à administrer des doses efficaces d'un ou plusieurs de ces sulfonamides ou promédicaments de ces derniers, qui inhibent l'activité de l'endothéline.

  提供了Thienyl，furyl和pyrrolyl-sulfonamides，这些药物的制剂和改变内皮素家族肽的活性或调节其活性的方法。特别地，提供了N-(异唑啉基)thienylsulfonamides，N-(异唑啉基)furylsulfonamides和N-(异唑啉基)pyrrolylsulfonamides，这些药物的制剂和使用这些磺酰胺类药物通过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类药物或其前药有效剂量来治疗内皮素介导的疾病的方法，这些药物能够抑制内皮素的活性。这些药物的药物制剂是药学上可接受的。
• The Synthesis, Acidity and Decarboxylation of Substituted Mesitoic Acids¹
  作者：F. Marshall Beringer、Seymour Sands

  DOI：10.1021/ja01110a008

  日期：1953.7
• CUYEGKENG M. A.; MANNSCHRECK A., CHEM. BER., 120,(1987) N 5, 803-809
  作者：CUYEGKENG M. A.、 MANNSCHRECK A.

  DOI：——

  日期：——
• SULFONAMIDES AND DERIVATIVES THEREOF THAT MODULATE THE ACTIVITY OF ENDOTHELIN
  申请人：TEXAS BIOTECHNOLOGY CORPORATION

  公开号：EP0946552A1

  公开（公告）日：1999-10-06
• Endothelin Antagonists:  Substituted Mesitylcarboxamides with High Potency and Selectivity for ET_A Receptors
  作者：Chengde Wu、E. Radford Decker、Natalie Blok、Huong Bui、Qi Chen、B. Raju、Andree R. Bourgoyne、Vippra Knowles、Ronald J. Biediger、Robert V. Market、Shuqun Lin、Brian Dupré、Timothy P. Kogan、George W. Holland、Tommy A. Brock、Richard A. F. Dixon

  DOI：10.1021/jm9900063

  日期：1999.11.1

  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.