ethyl 3-phenyl-5-(trifluoromethyl)isoxazole-4-carboxylate

• 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: ethyl 3-phenyl-5-(trifluoromethyl)isoxazole-4-carboxylate
• 英文别名: 4-ethoxycarbonyl-3-phenyl-5-trifluoromethyl-isoxazole；4-ethoxycarbonyl-3-phenyl-5-trifluoromethylisoxazole；3-Phenyl-5-(trifluoromethyl)isoxazole-4-carboxylic acid ethyl ester；ethyl 3-phenyl-5-(trifluoromethyl)-1,2-oxazole-4-carboxylate
• 化学式: C₁₃H₁₀F₃NO₃
• 分子量: 285.223
• InChiKey: BTTKBZODDAEFJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 3-phenyl-5-(trifluoromethyl)isoxazole-4-carboxylate 在 盐酸 、 溶剂黄146 作用下， 生成 3-phenyl-5-trifluoromethyl-isoxazole-4-carboxylic acid
  参考文献：
  名称：

  [EN] CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF
  [FR] MODULATEURS DE CALPAIN ET LEURS UTILISATIONS THÉRAPEUTIQUES

  摘要：

  公开号：

  WO2018064119A8
• 作为产物：
  描述：

  在 manganese(IV) oxide 作用下， 以 甲苯 为溶剂， 以100%的产率得到ethyl 3-phenyl-5-(trifluoromethyl)isoxazole-4-carboxylate
  参考文献：
  名称：

  有效的大规模合成BMS-520，有效和选择性的含异恶唑的S1P 1受体激动剂。

  摘要：

  本文报告了1-（4-（5-（3-苯基-4-（三氟甲基）异恶唑-5-基）-1,2,4-恶二唑-3-基）苄基）氮杂环丁烷的高效放大合成-3-羧酸（BMS-520），一种有效且选择性的含异恶唑的S1P 1受体激动剂。该方法的特点是具有高度区域选择性的环加成反应，生成关键中间体3-苯基-4-（三氟甲基）异恶唑-5-羧酸乙酯，其区域异构体的化学选择性水解以及改进的1,2,4方法-恶二唑的形成，相对于原始合成。改进后的工艺被用于制备多批次的BMS-520，用于临床前毒理学研究。

  DOI：

  10.1021/acs.oprd.6b00112

文献信息

• [EN] SPHINGOSINE-1-PHOSPHATE RECEPTOR AGONISTS<br/>[FR] AGONISTES DES RÉCEPTEURS SPHINGOSINE-1-PHOSPHATE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2011017578A1

  公开（公告）日：2011-02-10

  Disclosed are compounds of Formula (I), or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein: A is formula (II) Q is a substituted 5-membered monocyclic heteroaryl group; W is CH2, O, or NH; and R1, R2, R3, R4, R5, R6, m, n, t, and x are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, 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.

  揭示了Formula (I)的化合物，或其立体异构体或药用可接受的盐，其中：A为Formula (II)，Q为取代的5-成员单环杂芳基团；W为CH2、O或NH；而R1、R2、R3、R4、R5、R6、m、n、t和x在此处有定义。还揭示了将这些化合物用作G蛋白偶联受体S1P1的选择性激动剂的方法，以及包含这些化合物的药物组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或紊乱方面具有用处，如自身免疫疾病和血管疾病。
• Design, synthesis and SAR of a novel series of heterocyclic phenylpropanoic acids as GPR120 agonists
  作者：Xuqing Zhang、Chaozhong Cai、Michael Winters、Michele Wells、Mark Wall、James Lanter、Zhihua Sui、Jingyuan Ma、Aaron Novack、Imad Nashashibi、Yuanping Wang、Wen Yan、Arthur Suckow、Hong Hua、Austin Bell、Peter Haug、Wilma Clapper、Celia Jenkinson、Joseph Gunnet、James Leonard、William V. Murray

  DOI：10.1016/j.bmcl.2017.06.028

  日期：2017.8

  A novel series of 5-membered heterocycle-containing phenylpropanoic acid derivatives was discovered as potent GPR120 agonists with low clearance, high oral bioavailability and in vivo antidiabetic activity in rodents.

  发现了一系列新型的五元含杂环苯丙酸衍生物，作为强效的GPR120激动剂，在啮齿类动物中具有低清除率，高口服生物利用度和体内抗糖尿病活性。
• [EN] 4 - (5 - ISOXAZOLYL OR 5 - PYRRAZOLYL -1,2,4- OXADIAZOL - 3 - YL) -MANDELIC ACID AMIDES AS SPHINGOSIN- 1 - PHOSPHATE 1 RRECEPTOR AGONISTS<br/>[FR] AMIDES D'ACIDE 4-(5-ISOXAZOLYL OU 5-PYRAZOLYL-1,2,4-OXADIAZOL-3-YL)-MANDÉLIQUE COMME AGONISTES DU RÉCEPTEUR DE LA SPHINGOSINE-1-PHOSPHATE DE TYPE 1
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2011133734A1

  公开（公告）日：2011-10-27

  Disclosed are compounds of Formula (I) or stereoisomers, salts, or prodrugs thereof, wherein: Q is, or R1 is phenyl substituted with zero to 3 substituents; and R1, R2, R3, R4, R5, and G are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, 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.

  揭示了Formula (I)的化合物或其立体异构体、盐或前药，其中：Q是，或者R1是苯基，其上取代基为零至3个；而R1、R2、R3、R4、R5和G在此处有定义。还揭示了将这些化合物用作G蛋白偶联受体S1P1的选择性激动剂的方法，以及包含这些化合物的药物组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或紊乱方面具有用处，如自身免疫疾病和血管疾病。
• Synthesis of ethyl 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylate via regioselective dipolar cycloaddition
  作者：Michael A. Schmidt、Kishta Katipally、Antonio Ramirez、Omid Soltani、Xiaoping Hou、Huiping Zhang、Bang-Chi Chen、Xinhua Qian、Rajendra P. Deshpande

  DOI：10.1016/j.tetlet.2012.05.089

  日期：2012.8

  Efforts to prepare ethyl 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylate (1) by developing a regioselective 1,3-dipolar cycloaddition between phenyl nitrile oxide and various 4,4,4-trifluoromethyl crotonates are described. The substitution at the C2-position of crotonate dipolarophile 4 significantly influenced the regiochemistry and yield of the cycloaddition. Enol and enol ether-based crotonates

  努力以制备3-苯基-4-（三氟甲基）异恶唑-5-羧酸乙酯（1由显影苯基氧化腈和各种4,4,4-三氟巴豆酸酯之间的区域选择性1,3-偶极环加成）中有所描述。丁烯二酸4的巴豆酸酯C2位置的取代显着影响区域加成反应的区域化学和收率。烯醇和烯醇醚基的巴豆酸酯与苯基一氧化氮进行区域选择性环加成，以高收率提供4-三氟甲基异恶唑。
• [EN] HETEROCYCLIC COMPOUNDS AS S1P1 AGONISTS FOR THE TREATMENT OF AUTOIMMUNE AND VASCULAR DISEASES<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES UTILISÉS COMME AGONISTES DE S1P1 POUR LE TRAITEMENT DE MALADIES AUTO-IMMUNES ET VASCULAIRES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2012061459A1

  公开（公告）日：2012-05-10

  Disclosed are compounds of Formula (I) or stereoisomers, salts, or prodrugs thereof, wherein: W is CH2 or O; Q is Formula (II), Formula (III) or Formula (IV); and R1, R2, R3, R4, n, and G are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, 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.

  公开的是Formula (I)的化合物或其立体异构体、盐或前药，其中：W为CH2或O；Q为Formula (II)、Formula (III)或Formula (IV)；而R1、R2、R3、R4、n和G在此有所定义。还公开了将这些化合物用作选择性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药物组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或疾病的进展方面具有用途，如自身免疫疾病和血管疾病。