乙基3-(2-溴苯基)-5-甲基-1,2-恶唑-4-羧酸酯 | 848186-83-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 乙基3-(2-溴苯基)-5-甲基-1,2-恶唑-4-羧酸酯
• 英文名称: 3-(o-bromophenyl)-5-methylisoxazole-4-carboxylic acid ethyl ester
• 英文别名: Ethyl 3-(2-bromophenyl)-5-methylisoxazole-4-carboxylate；ethyl 3-(2-bromophenyl)-5-methyl-1,2-oxazole-4-carboxylate
• CAS: 848186-83-4
• 化学式: C₁₃H₁₂BrNO₃
• 分子量: 310.147
• InChiKey: SRLYCHULXLHBFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 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：
  4

反应信息

• 作为反应物：
  描述：

  乙基3-(2-溴苯基)-5-甲基-1,2-恶唑-4-羧酸酯 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以100%的产率得到3-(2-bromo-phenyl)-5-methyl-isoxazole-4-carboxylic acid
  参考文献：
  名称：

  Synthesis and structure–activity relationships of isoxazole carboxamides as growth hormone secretagogue receptor antagonists

  摘要：

  A series of isoxazole carboxamide derivatives has been developed as potent ghrelin receptor antagonists. The synthesis and structure-activity relationship (SAR) are described. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.11.075
• 作为产物：
  描述：

  2-溴苯甲醛肟 在 吡啶 、 N-氯代丁二酰亚胺 、 sodium 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 8.0h， 生成 乙基3-(2-溴苯基)-5-甲基-1,2-恶唑-4-羧酸酯
  参考文献：
  名称：

  Dimeric isoxazolyl-1,4-dihydropyridines have enhanced binding at the multi-drug resistance transporter

  摘要：

  A series of dimeric isoxazolyl-1,4-dihydropyridines (IDHPs) were prepared by click chemistry and examined for their ability to bind the multi-drug resistance transporter (MDR-1), a member of the ATP-binding cassette superfamily (ABC). Eight compounds in the present study exhibited single digit micromolar binding to this efflux transporter. One monomeric IDHP m-Br-1c, possessed submicromolar binding of 510 nM at MDR-1. Three of the dimeric IDHPs possessed <1.5 mu M activity, and 4b and 4c were observed to have superior binding selectivity compared to their corresponding monomers verses the voltage gated calcium channel (VGCC). The dimer with the best combination of activity and selectivity for MDR-1 was analog 4c containing an m-Br phenyl moiety in the 3-position of the isoxazole, and a tether with five ethyleneoxy units, referred to herein as Isoxaquidar. Two important controls, mono-triazole 5 and pyridine 6, also were examined, indicating that the triazole - incorporated as part of the click assembly as a spacer - contributes to MDR-1 binding. Compounds were also assayed at the allosteric site of the mGluR5 receptor, as a GPCR 7TM control, indicating that the p-Br IDHPs 4d, 4e and 4f with tethers of from n = 2 to 5 ethylenedioxy units, had sub-micromolar affinities with 4d being the most efficacious at 193 nM at mGluR5. The results are interpreted using a docking study using a human ABC as our current working hypothesis, and suggest that the distinct SARs emerging for these three divergent classes of biomolecular targets may be tunable, and amenable to the development of further selectivity. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.04.008

文献信息

• Dimeric isoxazolyl-1,4-dihydropyridines have enhanced binding at the multi-drug resistance transporter
  作者：Scott A. Steiger、Chun Li、Donald S. Backos、Philip Reigan、N.R. Natale

  DOI：10.1016/j.bmc.2017.04.008

  日期：2017.6

  A series of dimeric isoxazolyl-1,4-dihydropyridines (IDHPs) were prepared by click chemistry and examined for their ability to bind the multi-drug resistance transporter (MDR-1), a member of the ATP-binding cassette superfamily (ABC). Eight compounds in the present study exhibited single digit micromolar binding to this efflux transporter. One monomeric IDHP m-Br-1c, possessed submicromolar binding of 510 nM at MDR-1. Three of the dimeric IDHPs possessed <1.5 mu M activity, and 4b and 4c were observed to have superior binding selectivity compared to their corresponding monomers verses the voltage gated calcium channel (VGCC). The dimer with the best combination of activity and selectivity for MDR-1 was analog 4c containing an m-Br phenyl moiety in the 3-position of the isoxazole, and a tether with five ethyleneoxy units, referred to herein as Isoxaquidar. Two important controls, mono-triazole 5 and pyridine 6, also were examined, indicating that the triazole - incorporated as part of the click assembly as a spacer - contributes to MDR-1 binding. Compounds were also assayed at the allosteric site of the mGluR5 receptor, as a GPCR 7TM control, indicating that the p-Br IDHPs 4d, 4e and 4f with tethers of from n = 2 to 5 ethylenedioxy units, had sub-micromolar affinities with 4d being the most efficacious at 193 nM at mGluR5. The results are interpreted using a docking study using a human ABC as our current working hypothesis, and suggest that the distinct SARs emerging for these three divergent classes of biomolecular targets may be tunable, and amenable to the development of further selectivity. (C) 2017 Elsevier Ltd. All rights reserved.
• Synthesis and structure–activity relationships of isoxazole carboxamides as growth hormone secretagogue receptor antagonists
  作者：Zhili Xin、Hongyu Zhao、Michael D. Serby、Bo Liu、Verlyn G. Schaefer、Douglas H. Falls、Wiweka Kaszubska、Christine A. Colins、Hing L. Sham、Gang Liu

  DOI：10.1016/j.bmcl.2004.11.075

  日期：2005.2

  A series of isoxazole carboxamide derivatives has been developed as potent ghrelin receptor antagonists. The synthesis and structure-activity relationship (SAR) are described. (C) 2004 Elsevier Ltd. All rights reserved.