2,2-Dimethyl-propionic acid 4-benzyl-1-hydroxy-6-methyl-1,3-dihydro-furo[3,4-c]pyridin-7-yl ester | 860462-16-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2,2-Dimethyl-propionic acid 4-benzyl-1-hydroxy-6-methyl-1,3-dihydro-furo[3,4-c]pyridin-7-yl ester
• CAS: 860462-16-4
• 化学式: C₂₀H₂₃NO₄
• 分子量: 341.407
• InChiKey: BLQWVGLLVMYWGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.45
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  68.65
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2,2-Dimethyl-propionic acid 4-benzyl-1-hydroxy-6-methyl-1,3-dihydro-furo[3,4-c]pyridin-7-yl ester 在 氢氧化钾 、 氯化亚砜 作用下， 以 苯 为溶剂， 反应 72.25h， 生成 dimethyl (4-dimethoxymethyl-3-hydroxy-2-methyl-6-benzylpyrid-5-yl)methylphosphonate
  参考文献：
  名称：

  Synthesis of pyridoxal phosphate derivatives with antagonist activity at the P2Y13 receptor

  摘要：

  We have synthesized a series of derivatives of the known P2 receptor antagonist PPADS (pyridoxit-5'-phosphate-6-azo-phenyl-2.4-disulfonate) and examined their ability to inhibit functional activity of the recombinant human P2Ytt nucleotide receptor expressed in 1321N1 human astrocytoma cells co-expressing G alpha(16) protein (AG32). Analogues of PPADS modified through substitution of the phenylazo ring, including halo and nitro substitution, and 5'-alkyl phosphonate analogues were synthesized and tested. A 6-benzyl-5'-methyl phosphonate analogue was prepared to examine the effect of stable replacement of the azo linkage, The highest antagonistic poteney was observed for 6-(3-nitrophenylazo) derivatives of pyridoxal-5'-phosphate, The 2-chloro-5-nitro analogue (MRS 2211) and 4-chloro-3-nitro analogue (MRS 2603) inhibited ADP (100 nM)-induced inositol trisphosphate (IP3) formation with pIC(50) values of 5.97 and 6.18, respectively, being 45- and 74-fold more potent than PPADS. The antagonism of MRS 2211 was competitive with a pA(2) value of 6.3. MRS2211 and MRS2603 inhibited phospholipase C (PLC) responses to 30 nM 2-methylthio-ADP in human P2Y(1) receptor-mediated 1321N1 astrocytoma cells with IC50 values of > 10and 0.245 mu M, respectively. Both analogues were inactive(> 10 mu M) as antagonists of human P2Y(12) receptor-mediated PLC responses in 1321N1 astrocytoma cells, Thus. MRS2211 displayed > 20-fold selectivity as antagonist of the P2Y(13) receptor in comparison to P2Y(1) and P2Y12 receptors, while MRS2603 antagonized both P2Y(1) and P2Y(13), receptors. (c) 2005 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2005.04.021
• 作为产物：
  描述：

  3-trimethylmethylcarbonyl-6-(benzyl)pyridoxal monomethyl acetal 在 硫酸 作用下， 以 水 、 丙酮 为溶剂， 反应 48.0h， 以79%的产率得到2,2-Dimethyl-propionic acid 4-benzyl-1-hydroxy-6-methyl-1,3-dihydro-furo[3,4-c]pyridin-7-yl ester
  参考文献：
  名称：

  Synthesis of pyridoxal phosphate derivatives with antagonist activity at the P2Y13 receptor

  摘要：

  We have synthesized a series of derivatives of the known P2 receptor antagonist PPADS (pyridoxit-5'-phosphate-6-azo-phenyl-2.4-disulfonate) and examined their ability to inhibit functional activity of the recombinant human P2Ytt nucleotide receptor expressed in 1321N1 human astrocytoma cells co-expressing G alpha(16) protein (AG32). Analogues of PPADS modified through substitution of the phenylazo ring, including halo and nitro substitution, and 5'-alkyl phosphonate analogues were synthesized and tested. A 6-benzyl-5'-methyl phosphonate analogue was prepared to examine the effect of stable replacement of the azo linkage, The highest antagonistic poteney was observed for 6-(3-nitrophenylazo) derivatives of pyridoxal-5'-phosphate, The 2-chloro-5-nitro analogue (MRS 2211) and 4-chloro-3-nitro analogue (MRS 2603) inhibited ADP (100 nM)-induced inositol trisphosphate (IP3) formation with pIC(50) values of 5.97 and 6.18, respectively, being 45- and 74-fold more potent than PPADS. The antagonism of MRS 2211 was competitive with a pA(2) value of 6.3. MRS2211 and MRS2603 inhibited phospholipase C (PLC) responses to 30 nM 2-methylthio-ADP in human P2Y(1) receptor-mediated 1321N1 astrocytoma cells with IC50 values of > 10and 0.245 mu M, respectively. Both analogues were inactive(> 10 mu M) as antagonists of human P2Y(12) receptor-mediated PLC responses in 1321N1 astrocytoma cells, Thus. MRS2211 displayed > 20-fold selectivity as antagonist of the P2Y(13) receptor in comparison to P2Y(1) and P2Y12 receptors, while MRS2603 antagonized both P2Y(1) and P2Y(13), receptors. (c) 2005 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2005.04.021