3-(4-cyano-3-methyl-phenyl)-2-methyl-propionic acid tert-butyl ester | 929202-13-1

• 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: 3-(4-cyano-3-methyl-phenyl)-2-methyl-propionic acid tert-butyl ester
• CAS: 929202-13-1
• 化学式: C₁₆H₂₁NO₂
• 分子量: 259.348
• InChiKey: JSESPNNUTQCARP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  50.09
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3-(4-cyano-3-methyl-phenyl)-2-methyl-propionic acid tert-butyl ester 在 盐酸羟胺 、 碳酸氢钠 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 36.0h， 生成 3-(3-Methyl-4-{5-[4-(propan-2-yloxy)-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)butanoic acid
  参考文献：
  名称：

  SAR studies of 3-arylpropionic acids as potent and selective agonists of sphingosine-1-phosphate receptor-1 (S1P1) with enhanced pharmacokinetic properties

  摘要：

  Structure-activity relationship (SAR) studies of 3-arylpropionic acids-a class of novel S1P(1) selective agonists-by introducing substitution to the propionic acid chain and replacing the adjacent phenyl ring with pyridine led to a series of modified 3-arylpropionic acids with enhanced half-life in rat. These analogs (e.g., cyclopropanecarboxylic acids) exhibited longer half-life in rat than did unmodified 3-arylpropionic acids. This result suggests that metabolic oxidation at the propionic acid chain, particularly at the C3 benzylic position of 3-arylpropionic acids, is probably responsible for their short half-life in rodent. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.057
• 作为产物：
  描述：

  甲基丙烯酸叔丁酯 在 palladium on activated charcoal tris(dibenzylideneacetone)dipalladium (0) 、 N-甲基二环己基胺 、 氢气 、 2-(二叔丁基膦)联苯 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 20.0~80.0 ℃ 、101.33 kPa 条件下， 生成 3-(4-cyano-3-methyl-phenyl)-2-methyl-propionic acid tert-butyl ester
  参考文献：
  名称：

  SAR studies of 3-arylpropionic acids as potent and selective agonists of sphingosine-1-phosphate receptor-1 (S1P1) with enhanced pharmacokinetic properties

  摘要：

  Structure-activity relationship (SAR) studies of 3-arylpropionic acids-a class of novel S1P(1) selective agonists-by introducing substitution to the propionic acid chain and replacing the adjacent phenyl ring with pyridine led to a series of modified 3-arylpropionic acids with enhanced half-life in rat. These analogs (e.g., cyclopropanecarboxylic acids) exhibited longer half-life in rat than did unmodified 3-arylpropionic acids. This result suggests that metabolic oxidation at the propionic acid chain, particularly at the C3 benzylic position of 3-arylpropionic acids, is probably responsible for their short half-life in rodent. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.057

文献信息

• [EN] (3,4-DISUBSTITUTED)PROPANOIC CARBOXYLATES AS S1P (EDG) RECEPTOR AGONISTS<br/>[FR] CARBOXYLATES PROPANOIQUES 3,4-DISUSBSTITUES UTILISES EN TANT QU'AGONISTES DU RECEPTEUR S1P (EDG)
  申请人：MERCK & CO INC

  公开号：WO2005058848A1

  公开（公告）日：2005-06-30

  The present invention encompasses compounds of Formula A: A as well as the pharmaceutically acceptable salts thereof. The compounds are S1P1/Edg1 receptor agonists and thus have immunosuppressive, anti-inflammatory and hemostatic activities by modulating leukocyte trafficking, sequestering lymphocytes in secondary lymphoid tissues, and enhancing vascular integrity. The invention is also directed to pharmaceutical compositions containing such compounds and methods of treatment or prevention.

  本发明涵盖了化合物A的公式：A以及其药用可接受的盐。这些化合物是S1P1/Edg1受体激动剂，因此通过调节白细胞的运动、在次生淋巴组织中滞留淋巴细胞以及增强血管完整性而具有免疫抑制、抗炎和止血活性。该发明还涉及含有这些化合物的药物组合物以及治疗或预防的方法。