3-(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)acrylic acid | 1147-53-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)acrylic acid
• 英文别名: 3-(2,2,8-Trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)acrylic acid；3-(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)prop-2-enoic acid
• CAS: 1147-53-1
• 化学式: C₁₃H₁₅NO₄
• 分子量: 249.266
• InChiKey: CYRFGVHAXBLTLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  68.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)acrylic acid 在 盐酸 、 manganese(IV) oxide 、 Oxone 、 水 、 sodium carbonate 、 sodium nitrite 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 54.0h， 生成 3-(2-carboxyethyl)-5-hydroxy-6-methyl-2-((4-sulfophenyl)diazenyl)isonicotinic acid
  参考文献：
  名称：

  Synthesis and structure–activity relationships of carboxylic acid derivatives of pyridoxal as P2X receptor antagonists

  摘要：

  Carboxylic acid derivatives of pyridoxal were developed as potent P2X(1) and P2X(3) receptor antagonists with modifications of a lead compound, pyridoxal-5'-phosphate-6-azophenyl-2',5'-disulfonate (5b, iso-PPADS). The designing strategies included the modifications of aldehyde, phosphate or sulfonate groups of 5b, which may be interacted with lysine residues of the receptor binding pocket, to weak anionic carboxylic acid groups. The corresponding carboxylic acid analogs of pyridoxal-5'-phosphate (1), 13 and 14, showed parallel antagonistic potencies. Also, most of 6-azophenyl derivatives (24-28) of compound 13 or 14 showed potent antagonistic activities similar to that of 5b at human P2X(3) receptors with 100 nM range of IC50 values in two-electrode voltage clamp (TEVC) assay system on the Xenopus oocyte. The results indicated that aldehyde and phosphoric or sulfonic acids in 5b could be changed to a carboxylic acid without affecting antagonistic potency at mouse P2X(1) and human P2X(3) receptors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.073
• 作为产物：
  描述：

  2-甲基-3-羟基-4,5-二羟甲基吡啶 在 重铬酸吡啶 、 水 、 sodium hydride 、 对甲苯磺酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 mineral oil 为溶剂， 反应 4.58h， 生成 3-(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)acrylic acid
  参考文献：
  名称：

  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

  摘要：

  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。

  公开号：

  US20130040997A1

文献信息

• Pyridoxine Chemistry. VI. Homologs of Pyridoxol and of 5-Pyridoxic Acid^1,2
  作者：W. Korytnyk

  DOI：10.1021/jm00325a023

  日期：1965.1
• Synthesis and structure–activity relationships of carboxylic acid derivatives of pyridoxal as P2X receptor antagonists
  作者：Kwan-Young Jung、Joong-Heui Cho、Jung Sun Lee、Hyo Jun Kim、Yong-Chul Kim

  DOI：10.1016/j.bmc.2013.01.073

  日期：2013.5

  Carboxylic acid derivatives of pyridoxal were developed as potent P2X(1) and P2X(3) receptor antagonists with modifications of a lead compound, pyridoxal-5'-phosphate-6-azophenyl-2',5'-disulfonate (5b, iso-PPADS). The designing strategies included the modifications of aldehyde, phosphate or sulfonate groups of 5b, which may be interacted with lysine residues of the receptor binding pocket, to weak anionic carboxylic acid groups. The corresponding carboxylic acid analogs of pyridoxal-5'-phosphate (1), 13 and 14, showed parallel antagonistic potencies. Also, most of 6-azophenyl derivatives (24-28) of compound 13 or 14 showed potent antagonistic activities similar to that of 5b at human P2X(3) receptors with 100 nM range of IC50 values in two-electrode voltage clamp (TEVC) assay system on the Xenopus oocyte. The results indicated that aldehyde and phosphoric or sulfonic acids in 5b could be changed to a carboxylic acid without affecting antagonistic potency at mouse P2X(1) and human P2X(3) receptors. (C) 2013 Elsevier Ltd. All rights reserved.
• 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。