5-ethoxy-4-methyl-2-phenethyl-oxazole | 1345962-73-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-ethoxy-4-methyl-2-phenethyl-oxazole
• 英文别名: 5-ethoxy-4-methyl-2-phenethyloxazole；5-Ethoxy-4-methyl-2-(2-phenylethyl)-1,3-oxazole；5-ethoxy-4-methyl-2-(2-phenylethyl)-1,3-oxazole
• CAS: 1345962-73-3
• 化学式: C₁₄H₁₇NO₂
• 分子量: 231.294
• InChiKey: ZPFMGKJAFSUMJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  35.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-ethoxy-4-methyl-2-phenethyl-oxazole 在 盐酸 、 水 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 11.0h， 生成 5-hydroxy-6-methyl-2-phenethylpyridine-3,4-dicarboxylic acid
  参考文献：
  名称：

  Design and synthesis of potent and selective P2X3 receptor antagonists derived from PPADS as potential pain modulators

  摘要：

  Pyridoxalphosphate-6-azopheny1-2',4'-disulfonate (7a, PPADS), a nonselective P2X receptor antagonist, was extensively modified to develop more stable, potent, and selective P2X(3) receptor antagonists as potential antinociceptive agents. Based on the results of our previous report, all strong anionic groups in PPADS including phosphate and sulfonate groups were changed to carboxylic acids or deleted. The unstable azo (-N=N-) linkage of 7a was transformed to more stable carbon-carbon, ether or amide linkages through the synthesis of the 5-hydroxyl-pyridine moieties with substituents at 2 position via a Diels-Alder reaction. This resulted in the retention of antagonistic activity (IC50 = 400 similar to 700 nM) at the hP2X(3) receptor in the two-electrode voltage clamp (TEVC) assay system on the Xenopus oocytes. Introduction of bulky aromatic groups at the carbon linker, as in compounds 13h-n, dramatically improved the selectivity profiles of hP2X(3) when compared with mP2X(1) and hP2X(7) receptors. Among the substituents tested at the 2-position, the m-phenoxybenzyl group showed optimum selectivity and potency at the hP2X(3) receptor. In searching for effective substituents at the 4- and 3-positions, we found that compound 36j, with 4-carboxaldehyde, 3-propenoic acid and 2-(m-phenoxy)benzyl groups, was the most potent and selective hP2X(3) receptor antagonist with an IC50 of 60 nM at hP2X(3) and marginal antagonistic activities of 10 mu M at mP2X(1) and hP2X(7). Furthermore, using an ex-vivo assay system, we found that compound 36j potently inhibited pain signaling in the rat dorsal horn with 20 mu M 36j displaying 65% inhibition while 20 mu M pregabalin, a clinically available drug, showed only 31% inhibition. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.10.026
• 作为产物：
  描述：

  L-丙氨酸乙酯 在 四磷十氧化物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 16.0h， 生成 5-ethoxy-4-methyl-2-phenethyl-oxazole
  参考文献：
  名称：

  Design and synthesis of potent and selective P2X3 receptor antagonists derived from PPADS as potential pain modulators

  摘要：

  Pyridoxalphosphate-6-azopheny1-2',4'-disulfonate (7a, PPADS), a nonselective P2X receptor antagonist, was extensively modified to develop more stable, potent, and selective P2X(3) receptor antagonists as potential antinociceptive agents. Based on the results of our previous report, all strong anionic groups in PPADS including phosphate and sulfonate groups were changed to carboxylic acids or deleted. The unstable azo (-N=N-) linkage of 7a was transformed to more stable carbon-carbon, ether or amide linkages through the synthesis of the 5-hydroxyl-pyridine moieties with substituents at 2 position via a Diels-Alder reaction. This resulted in the retention of antagonistic activity (IC50 = 400 similar to 700 nM) at the hP2X(3) receptor in the two-electrode voltage clamp (TEVC) assay system on the Xenopus oocytes. Introduction of bulky aromatic groups at the carbon linker, as in compounds 13h-n, dramatically improved the selectivity profiles of hP2X(3) when compared with mP2X(1) and hP2X(7) receptors. Among the substituents tested at the 2-position, the m-phenoxybenzyl group showed optimum selectivity and potency at the hP2X(3) receptor. In searching for effective substituents at the 4- and 3-positions, we found that compound 36j, with 4-carboxaldehyde, 3-propenoic acid and 2-(m-phenoxy)benzyl groups, was the most potent and selective hP2X(3) receptor antagonist with an IC50 of 60 nM at hP2X(3) and marginal antagonistic activities of 10 mu M at mP2X(1) and hP2X(7). Furthermore, using an ex-vivo assay system, we found that compound 36j potently inhibited pain signaling in the rat dorsal horn with 20 mu M 36j displaying 65% inhibition while 20 mu M pregabalin, a clinically available drug, showed only 31% inhibition. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.10.026

文献信息

• Thermally Controlled Decarboxylative [4 + 2] Cycloaddition between Alkoxyoxazoles and Acrylic Acid: Expedient Access to 3-Hydroxypyridines
  作者：Laurie-Anne Jouanno、Vincent Tognetti、Laurent Joubert、Cyrille Sabot、Pierre-Yves Renard

  DOI：10.1021/ol4010195

  日期：2013.5.17

  A modified Kondrat’eva cycloaddition involving an unprecedented thermally controlled metal-free decarboxylative aromatization affords an expedient access to natural 3-hydroxypyridine/piperidine systems.

  改性的Kondrat'eva环加成反应涉及前所未有的热控制的无金属脱羧芳构化，可方便地获得天然3-羟基吡啶/哌啶体系。
• Metal-Free Decarboxylative Hetero-Diels–Alder Synthesis of 3-Hydroxypyridines: A Rapid Access to <i>N</i>-Fused Bicyclic Hydroxypiperidine Scaffolds
  作者：Laurie-Anne Jouanno、Vincent Di Mascio、Vincent Tognetti、Laurent Joubert、Cyrille Sabot、Pierre-Yves Renard

  DOI：10.1021/jo402729a

  日期：2014.2.7

  A complete experimental and theoretical study of the thermally controlled metal-free decarboxylative hetero-Diels–Alder (HDA) reaction of 5-alkoxyoxazoles with acrylic acid is reported. This strategy offers a new entry to valuable 2,6-difunctionalized 3-hydroxypyridines from readily available 2- and 4-disubstituted 5-alkoxyoxazoles. The reaction conditions proved compatible with, among others, ketone

  报道了5-烷氧基恶唑与丙烯酸热控制的无金属脱羧杂狄尔斯-阿尔德（HDA）反应的完整实验和理论研究。该策略为易于获得的2-和4-二取代的5-烷氧基恶唑提供了有价值的2,6-二官能化的3-羟基吡啶的新入口。证明该反应条件尤其与酮，酰胺，酯，醚和腈基相容。该方案具有广泛的官能团耐受性，可通过吡啶脱芳构化策略快速而通用地获得羟基吲哚并咪唑和羟基喹oli嗪衍生物。
• NOVEL PYRIDINE CARBOXYLIC ACID BASED COMPOUND USED AS A P2X1 AND P2X3 RECEPTOR ANTAGONIST, A PRODUCTION METHOD FOR THE SAME AND A COMPOSITION COMPRISING THE SAME
  申请人：Kim Yong-Chul

  公开号：US20130040997A1

  公开（公告）日：2013-02-14

  Provided are a novel pyridine carboxylic acid based compound used as a P2X 1 and P2X 3 receptor antagonist, a production method for the same and a composition comprising the same. The compound according to the present invention is a powerful antagonist of P2X 1 and P2X 3 receptors, and hence can be used as a drug for treating or preventing diseases involving neurological pain or chronic inflammatory diseases which are diseases caused by P2X 1 and P2X 3 receptor activity.

  提供了一种基于吡啶羧酸的新型化合物，用作P2X1和P2X3受体拮抗剂，以及该化合物的生产方法和包含该化合物的组合物。根据本发明的化合物是P2X1和P2X3受体的强效拮抗剂，因此可用作治疗或预防涉及神经疼痛或慢性炎症疾病的药物，这些疾病是由P2X1和P2X3受体活性引起的疾病。
• US9546139B2
  申请人：——

  公开号：US9546139B2

  公开（公告）日：2017-01-17
• Design and synthesis of potent and selective P2X3 receptor antagonists derived from PPADS as potential pain modulators
  作者：Joong-Heui Cho、Kwan-Young Jung、Younghwan Jung、Min Hye Kim、Hyojin Ko、Chul-Seung Park、Yong-Chul Kim

  DOI：10.1016/j.ejmech.2013.10.026

  日期：2013.12

  Pyridoxalphosphate-6-azopheny1-2',4'-disulfonate (7a, PPADS), a nonselective P2X receptor antagonist, was extensively modified to develop more stable, potent, and selective P2X(3) receptor antagonists as potential antinociceptive agents. Based on the results of our previous report, all strong anionic groups in PPADS including phosphate and sulfonate groups were changed to carboxylic acids or deleted. The unstable azo (-N=N-) linkage of 7a was transformed to more stable carbon-carbon, ether or amide linkages through the synthesis of the 5-hydroxyl-pyridine moieties with substituents at 2 position via a Diels-Alder reaction. This resulted in the retention of antagonistic activity (IC50 = 400 similar to 700 nM) at the hP2X(3) receptor in the two-electrode voltage clamp (TEVC) assay system on the Xenopus oocytes. Introduction of bulky aromatic groups at the carbon linker, as in compounds 13h-n, dramatically improved the selectivity profiles of hP2X(3) when compared with mP2X(1) and hP2X(7) receptors. Among the substituents tested at the 2-position, the m-phenoxybenzyl group showed optimum selectivity and potency at the hP2X(3) receptor. In searching for effective substituents at the 4- and 3-positions, we found that compound 36j, with 4-carboxaldehyde, 3-propenoic acid and 2-(m-phenoxy)benzyl groups, was the most potent and selective hP2X(3) receptor antagonist with an IC50 of 60 nM at hP2X(3) and marginal antagonistic activities of 10 mu M at mP2X(1) and hP2X(7). Furthermore, using an ex-vivo assay system, we found that compound 36j potently inhibited pain signaling in the rat dorsal horn with 20 mu M 36j displaying 65% inhibition while 20 mu M pregabalin, a clinically available drug, showed only 31% inhibition. (C) 2013 Elsevier Masson SAS. All rights reserved.