methyl 4-methyl-3-phenylisoxazole-5-carboxylate | 30408-26-5

• 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 4-methyl-3-phenylisoxazole-5-carboxylate
• 英文别名: 4-methyl-3-phenyl-isoxazole-5-carboxylic acid methyl ester；3-Phenyl-4-methyl-isoxazol-5-carbonsaeure-methylester；4-Methyl-3-Phenyl-5-isoxazol-carbonsaeure-methylester；4-Methyl-3-phenyl-isoxazole-5-carboxylicacidmethylester；methyl 4-methyl-3-phenyl-1,2-oxazole-5-carboxylate
• CAS: 30408-26-5
• 化学式: C₁₂H₁₁NO₃
• 分子量: 217.224
• InChiKey: SAZXQIDSHBCZDF-UHFFFAOYSA-N

物化性质

• 沸点：
  350.7±30.0 °C(Predicted)
• 密度：
  1.174±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-methyl-3-phenylisoxazole-5-carboxylate 在 lithium hydroxide monohydrate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 74.0h， 生成 1-(4-(5-(4-methyl-3-phenylisoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid,trifluoroacetic acid salt
  参考文献：
  名称：

  Potent and Selective Agonists of Sphingosine 1-Phosphate 1 (S1P₁): Discovery and SAR of a Novel Isoxazole Based Series

  摘要：

  Sphingosine 1-phosphate (S1P) is the endogenous ligand for the sphingosine 1-phosphate receptors (S1P(1-5)) and evokes a variety of cellular responses through their stimulation. The interaction of S1P with the S1P receptors plays a fundamental physiological role in a number of processes including vascular development and stabilization, lymphocyte migration, and proliferation. Agonism of S1P(1), in particular, has been shown to play a significant role in lymphocyte trafficking from the thymus and secondary lymphoid organs, resulting in immunosuppression. This article will detail the discovery and SAR of a potent and selective series of isoxazole based full agonists of S1P(1). Isoxazole 6d demonstrated impressive efficacy when administered orally in a rat model of arthritis and in a mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis.

  DOI：

  10.1021/acs.jmedchem.6b00089
• 作为产物：
  描述：

  巴豆酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 三乙胺 作用下， 以 四氯化碳 、 乙醚 为溶剂， 反应 1.33h， 生成 methyl 4-methyl-3-phenylisoxazole-5-carboxylate
  参考文献：
  名称：

  Christl,M. et al., Chemische Berichte, 1973, vol. 106, p. 3275 - 3290

  摘要：

  DOI：

文献信息

• TRICYCLIC HETEROCYCLIC COMPOUNDS
  申请人：Dhar T.G. Murali

  公开号：US20120214767A1

  公开（公告）日：2012-08-23

  Disclosed are compounds of Formula (I) or stereoisomers or salts thereof, wherein: X 1 , X 2 , X 3 , W, Q 1 , Q 2 , and G 2 are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P 1 , and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

  本发明涉及公式（I）的化合物或其立体异构体或盐，其中：X1、X2、X3、W、Q1、Q2和G2在此定义。还公开了使用这些化合物作为选择性G蛋白偶联受体S1P1的激动剂的方法，以及包含这些化合物的制药组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或障碍方面有用，例如自身免疫性疾病和血管疾病。
• Battioni,P. et al., Bulletin de la Societe Chimique de France, 1978, vol. <II>, p. 415 - 427
  作者：Battioni,P. et al.

  DOI：——

  日期：——
• US9216972B2
  申请人：——

  公开号：US9216972B2

  公开（公告）日：2015-12-22
• Christl,M. et al., Chemische Berichte, 1973, vol. 106, p. 3275 - 3290
  作者：Christl,M. et al.

  DOI：——

  日期：——
• Potent and Selective Agonists of Sphingosine 1-Phosphate 1 (S1P₁): Discovery and SAR of a Novel Isoxazole Based Series
  作者：Scott H. Watterson、Junqing Guo、Steve H. Spergel、Charles M. Langevine、Robert V. Moquin、Ding Ren Shen、Melissa Yarde、Mary Ellen Cvijic、Dana Banas、Richard Liu、Suzanne J. Suchard、Kathleen Gillooly、Tracy Taylor、Sandra Rex-Rabe、David J. Shuster、Kim W. McIntyre、Georgia Cornelius、Celia D’Arienzo、Anthony Marino、Praveen Balimane、Bethanne Warrack、Luisa Salter-Cid、Murray McKinnon、Joel C. Barrish、Percy H. Carter、William J. Pitts、Jenny Xie、Alaric J. Dyckman

  DOI：10.1021/acs.jmedchem.6b00089

  日期：2016.3.24

  Sphingosine 1-phosphate (S1P) is the endogenous ligand for the sphingosine 1-phosphate receptors (S1P(1-5)) and evokes a variety of cellular responses through their stimulation. The interaction of S1P with the S1P receptors plays a fundamental physiological role in a number of processes including vascular development and stabilization, lymphocyte migration, and proliferation. Agonism of S1P(1), in particular, has been shown to play a significant role in lymphocyte trafficking from the thymus and secondary lymphoid organs, resulting in immunosuppression. This article will detail the discovery and SAR of a potent and selective series of isoxazole based full agonists of S1P(1). Isoxazole 6d demonstrated impressive efficacy when administered orally in a rat model of arthritis and in a mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis.