methyl 4-bromo-5-phenylisoxazole-3-carboxylate

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 英文名称: methyl 4-bromo-5-phenylisoxazole-3-carboxylate
• 英文别名: methyl 4-bromo-5-phenyl-1,2-oxazole-3-carboxylate
• 化学式: C₁₁H₈BrNO₃
• 分子量: 282.093
• InChiKey: DHRDTTPZVUTSRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 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-bromo-5-phenylisoxazole-3-carboxylate 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 4,5-diphenylisoxazole-3-carboxylic acid
  参考文献：
  名称：

  Structure-Based Design of MptpB Inhibitors That Reduce Multidrug-Resistant Mycobacterium tuberculosis Survival and Infection Burden in Vivo

  摘要：

  Mycobacterium tuberculosis protein-tyrosine-phosphatase B (MptpB) is a secreted virulence factor that subverts antimicrobial activity in the host. We report here the structure-based design of selective MptpB inhibitors that reduce survival of multidrug-resistant tuberculosis strains in macrophages and enhance killing efficacy by first-line antibiotics. Monotherapy with an orally bioavailable MptpB inhibitor reduces infection burden in acute and chronic guinea pig models and improves the overall pathology. Our findings provide a new paradigm for tuberculosis treatment.

  DOI：

  10.1021/acs.jmedchem.8b00832
• 作为产物：
  描述：

  2,4-二氧代-4-苯丁酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 盐酸羟胺 作用下， 以 甲醇 、 三氟乙酸 为溶剂， 反应 72.0h， 生成 methyl 4-bromo-5-phenylisoxazole-3-carboxylate
  参考文献：
  名称：

  Structure-Based Design of MptpB Inhibitors That Reduce Multidrug-Resistant Mycobacterium tuberculosis Survival and Infection Burden in Vivo

  摘要：

  Mycobacterium tuberculosis protein-tyrosine-phosphatase B (MptpB) is a secreted virulence factor that subverts antimicrobial activity in the host. We report here the structure-based design of selective MptpB inhibitors that reduce survival of multidrug-resistant tuberculosis strains in macrophages and enhance killing efficacy by first-line antibiotics. Monotherapy with an orally bioavailable MptpB inhibitor reduces infection burden in acute and chronic guinea pig models and improves the overall pathology. Our findings provide a new paradigm for tuberculosis treatment.

  DOI：

  10.1021/acs.jmedchem.8b00832

文献信息

• [EN] SUBSTITUTED OXADIAZOLE DERIVATIVES AS S1P AGONISTS IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISEASES<br/>[FR] DÉRIVÉS D'OXADIAZOLE SUBSTITUÉS COMME AGONISTES DE S1P DANS LE TRAITEMENT DE MALADIES AUTO-IMMUNES ET INFLAMMATOIRES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010085581A1

  公开（公告）日：2010-07-29

  Disclosed are compounds of Formula (I) [INSERT CHEMICAL STRUCTURE HERE] (I) or pharmaceutically acceptable salts thereof, wherein Q is [INSERT CHEMICAL STRUCTURE HERE] or [INSERT CHEMICAL STRUCTURE HERE]; R1 is alkyl or aryl, said aryl optionally substituted with one to five substituents independently selected from C1 to C6 alkyl, C1 to C4 haloalkyl, OR4, and/or halogen; and R2, R3, R4, and n 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.

  揭示了化合物的结构式 (I) [在此插入化学结构] (I) 或其药学上可接受的盐，其中 Q 是 [在此插入化学结构] 或 [在此插入化学结构]；R1 是烷基或芳基，所述芳基可选择性地取代一个至五个取代基，独立选择自 C1 至 C6 烷基、C1 至 C4 卤代烷基、OR4 和/或卤素；而 R2、R3、R4 和 n 在此有定义。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疾病进展方面具有用途，如自身免疫疾病和血管疾病。
• A fast and efficient bromination of isoxazoles and pyrazoles by microwave irradiation
  作者：Guo Li、Ramesh Kakarla、Samuel W. Gerritz

  DOI：10.1016/j.tetlet.2007.04.118

  日期：2007.6

  fast and efficient method has been developed for the bromination of isoxazoles and pyrazoles using microwave irradiation. In this method, N-bromosuccinimide was used in different acid solvents according to the reactivity of the substrates to give mono-brominated isoxazoles and pyrazoles in good yields. Trifluoroacetic acid was found to be the best solvent for highly unreactive isoxazoles and pyrazoles

  已经开发出一种快速有效的方法，利用微波辐射将异恶唑和吡唑溴化。在该方法中，根据底物的反应性，在不同的酸性溶剂中使用N-溴琥珀酰亚胺，以高收率得到单溴代异恶唑和吡唑。发现三氟乙酸是高度不反应的异恶唑和吡唑的最佳溶剂。
• Reactivity of 2-Halo-2H-azirines. Part II. Thermal Ring Expansion Reactions: Synthesis of 4-Haloisoxazoles
  作者：Teresa M. V. D. Pinho e Melo、Cláudia S. J. Lopes、António M. d’A. Rocha Gonsalves、Richard C. Storr

  DOI：10.1055/s-2002-23542

  日期：——

  The thermolysis of haloazidoalkenes and 2-halo-2H-azirines is described. 2-Benzoyl-2-halo-2H-azirine-3-carboxylates (2a and 2b) underwent ring expansion leading to the synthesis of new 4-haloisoxazoles in high yield. The same isoxazoles were also obtained in high yield directly from haloazidoalkenes (la and 1b). The thermolysis of the β-azido-α,β-unsaturated ketone 1e led to complete conversion to

  描述了卤代叠氮化物和 2-卤代-2H-氮杂环丙烷的热解。2-Benzoyl-2-halo-2H-azirine-3-carboxylates（2a 和 2b）经历了扩环，导致以高产率合成新的 4-haloisoxazoles。同样的异恶唑也可以直接从卤代叠氮烯烃中以高产率获得（la 和 1b）。β-叠氮基-α,β-不饱和酮1e的热解导致完全转化形成相应的异恶唑4e。他还可以从 2-溴-3-苯基-2H-氮杂环丙烷-2-羧酸盐 (1c) 以中等收率获得异恶唑衍生物 4c。从叠氮基烯烃Id的热解中，唯一可以分离的产物是吡嗪-2,3,5,6-四羧酸盐(5)。
• SUBSTITUTED ISOXAZOLE COMPOUNDS
  申请人：Watterson Scott Hunter

  公开号：US20110300165A1

  公开（公告）日：2011-12-08

  Disclosed are compounds of Formula (I) or pharmaceutically acceptable salts thereof, wherein Q is R 1 is alkyl or aryl, said aryl optionally substituted with one to five substituents independently selected from C 1 to C 6 alkyl, C 1 to C 4 haloalkyl, —OR 4 , and/or halogen; and R 2 , R 3 , R 4 , and n 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）化合物或其药学上可接受的盐，其中Q是R1是烷基或芳基，所述芳基可选择性地被1到5个独立选择的取代基所取代，所述取代基选择自C1到C6烷基，C1到C4卤代烷基，-OR4和/或卤素; R2、R3、R4和n在此被定义。本发明还涉及使用这些化合物作为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制药组合物。这些化合物在多种治疗领域中有用，例如自身免疫性疾病和血管疾病的治疗、预防或减缓疾病或障碍的进展。
• Substituted isoxazole compounds
  申请人：Watterson Scott Hunter

  公开号：US08354398B2

  公开（公告）日：2013-01-15

  Disclosed are compounds of Formula (I) or pharmaceutically acceptable salts thereof, wherein Q is R1 is alkyl or aryl, said aryl optionally substituted with one to five substituents independently selected from C1 to C6 alkyl, C1 to C4 haloalkyl, —OR4, and/or halogen; and R2, R3, R4, and n 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.

  本发明涉及以下化合物（I）或其药学上可接受的盐，其中Q为R1为烷基或芳基，所述芳基可选地被一到五个取自C1到C6烷基，C1到C4卤代烷基，—OR4和/或卤素的取代基取代；而R2、R3、R4和n在此定义。本发明还涉及使用这些化合物作为选择性G蛋白偶联受体S1P1激动剂的方法，以及包含这些化合物的药物组合物。这些化合物在多种治疗领域中有用，例如自身免疫性疾病和血管疾病的治疗、预防或减缓疾病或疾病进展。