(R)-6-(hydroxymethyl)-2-(2-phenylethyl)-4,5,6,7-tetrahydropyrazolo[4,3-e][1,4]diazepin-8(2H)-one | 1198319-68-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-6-(hydroxymethyl)-2-(2-phenylethyl)-4,5,6,7-tetrahydropyrazolo[4,3-e][1,4]diazepin-8(2H)-one
• CAS: 1198319-68-4
• 化学式: C₁₅H₁₈N₄O₂
• 分子量: 286.334
• InChiKey: IRGUGLKRDXGQDS-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.64
• 重原子数：
  21.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  79.18
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  异喹啉-5-甲酸 、 (R)-6-(hydroxymethyl)-2-(2-phenylethyl)-4,5,6,7-tetrahydropyrazolo[4,3-e][1,4]diazepin-8(2H)-one 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (R)-(8-oxo-2-(2-phenethyl)-2,4,5,6,7,8-hexahydropyrazolo[4,3-e][1,4]diazepin-6-yl)methyl isoquinoline-5-carboxylate
  参考文献：
  名称：

  Synthesis and structure–activity relationships of pyrazolodiazepine derivatives as human P2X7 receptor antagonists

  摘要：

  Screening of library compounds has yielded pyrazolodiazepine derivatives with P2X(7) receptor antagonist activity. To explore the structure -activity relationships (SAR) of these pyrazolodiazepines as human P2X(7) receptor antagonists, derivatives were synthesized by substitutions at positions R-2 and R-3 of the pyrazolodiazepine skeleton. Using a 2'(3')-O-(4-benzoylbenzoyl)ATP (BzATP)-induced fluorescent ethidium uptake assay, the activities of these derivatives were tested in HEK-293 cells stably expressing human P2X(7) receptors. Moreover, the effect of these derivatives was assessed by measuring their effect on IL-1 beta release induced by BzATP-induced activation of differentiated THP-1 cells. A 2-phenethyl pyrazolodiazepine derivative with a 1-methyl-1H-3-indolyl group at position R-2 had fivefold greater activity than the derivative with a 5-isoquinolinyl at R-2. Moreover, a benzyl moiety at R-3 had fivefold greater activity than a bicyclic moiety. The stereochemical effect at C-6 showed a preference for the (R)-isomer. Among the series of active derivatives, compound 23b, with a phenethyl group at R-1, a 3-methyl indole at R-2, and a benzyl at R-3, exhibited activity similar to that of the positive control, KN-62, as shown by the inhibitory effects of IL-1 beta release. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.09.053
• 作为产物：
  描述：

  (R)-6-(tert-butoxymethyl)-2-phenethyl-4,5,6,7-tetrahydropyrazolo[4,3-e][1,4]diazepin-8(2H)-one 在 苯甲醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以85%的产率得到(R)-6-(hydroxymethyl)-2-(2-phenylethyl)-4,5,6,7-tetrahydropyrazolo[4,3-e][1,4]diazepin-8(2H)-one
  参考文献：
  名称：

  Synthesis and structure–activity relationships of pyrazolodiazepine derivatives as human P2X7 receptor antagonists

  摘要：

  Screening of library compounds has yielded pyrazolodiazepine derivatives with P2X(7) receptor antagonist activity. To explore the structure -activity relationships (SAR) of these pyrazolodiazepines as human P2X(7) receptor antagonists, derivatives were synthesized by substitutions at positions R-2 and R-3 of the pyrazolodiazepine skeleton. Using a 2'(3')-O-(4-benzoylbenzoyl)ATP (BzATP)-induced fluorescent ethidium uptake assay, the activities of these derivatives were tested in HEK-293 cells stably expressing human P2X(7) receptors. Moreover, the effect of these derivatives was assessed by measuring their effect on IL-1 beta release induced by BzATP-induced activation of differentiated THP-1 cells. A 2-phenethyl pyrazolodiazepine derivative with a 1-methyl-1H-3-indolyl group at position R-2 had fivefold greater activity than the derivative with a 5-isoquinolinyl at R-2. Moreover, a benzyl moiety at R-3 had fivefold greater activity than a bicyclic moiety. The stereochemical effect at C-6 showed a preference for the (R)-isomer. Among the series of active derivatives, compound 23b, with a phenethyl group at R-1, a 3-methyl indole at R-2, and a benzyl at R-3, exhibited activity similar to that of the positive control, KN-62, as shown by the inhibitory effects of IL-1 beta release. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.09.053