3-(2-thienylmethoxycarbonyl)-8-(N-Boc-pyrrol-2-yl)-pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide | 1310053-62-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(2-thienylmethoxycarbonyl)-8-(N-Boc-pyrrol-2-yl)-pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide
• 英文别名: Thiophen-2-ylmethyl 8-[1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrol-2-yl]-5-oxidopyrazolo[5,1-c][1,2,4]benzotriazin-5-ium-3-carboxylate
• CAS: 1310053-62-3
• 化学式: C₂₄H₂₁N₅O₅S
• 分子量: 491.527
• InChiKey: GZGFODOTTXFCJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  141
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-(2-thienylmethoxycarbonyl)-8-(N-Boc-pyrrol-2-yl)-pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 在 甲醇 、 sodium methylate 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以69%的产率得到3-methoxycarbonyl-8-(pyrrol-2-yl)pyrazolo[5,1-c][1,2,4]-benzotriazine 5-oxide
  参考文献：
  名称：

  New 3-, 8-disubstituted pyrazolo[5,1-c][1,2,4]benzotriazines useful for studying the interaction with the HBp-3 area (hydrogen bond point area) in the benzodiazepine site on the γ-aminobutyric acid type A (GABAA) receptor

  摘要：

  The pharmacophoric model using ADLR procedure, based on pyrazolo[5,1-c][1,2,4]benzotriazine system, studied in our laboratory, allowed us to identify the essential interaction points (HBp-1, HBp-2, and Lp-1) and the important areas for affinity modulation (HBp-3 and Lp-2) for binding recognition at benzodiazepine (Bzs) site of GABA(A) receptors (GABA(A)-Rs). In this work ADLR method is used to rationalize the affinity data of 23 new compounds and to improve the knowledge on HBp-3 area, hydrogen bond area. Among these new compounds emerge the pyrrolo derivatives (18, 25, 28, 34, and 37) for their good affinity value (14.9 > K-i(nM) > 63.0). In the orientations proposed by ADLR, the NH moiety of the pyrrole ring, independently of the position in the pyrazolobenzotriazine core, fits in HBp-3 area and points out the acceptor feature of this hydrogen bond area, already known as donor area. Unexpectedly, the oxygen atom of the furane ring does not form efficient hydrogen bond with the same area, probably for an imperfect distance. The size of substituent at position 8 is important but not necessary for the receptor recognition, in fact the interdependence between the features of the 3- and 8-substituent's is again verified, (i.e., compound 20 vs 32). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.009
• 作为产物：
  描述：

  3-(2-thienylmethoxycarbonyl)-8-iodopyrazolo[5,1-c]-[1,2,4]benzotriazine 5-oxide 、 1-Boc-吡咯-2-硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 水 、 甲苯 为溶剂， 反应 3.0h， 以80%的产率得到3-(2-thienylmethoxycarbonyl)-8-(N-Boc-pyrrol-2-yl)-pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide
  参考文献：
  名称：

  New 3-, 8-disubstituted pyrazolo[5,1-c][1,2,4]benzotriazines useful for studying the interaction with the HBp-3 area (hydrogen bond point area) in the benzodiazepine site on the γ-aminobutyric acid type A (GABAA) receptor

  摘要：

  The pharmacophoric model using ADLR procedure, based on pyrazolo[5,1-c][1,2,4]benzotriazine system, studied in our laboratory, allowed us to identify the essential interaction points (HBp-1, HBp-2, and Lp-1) and the important areas for affinity modulation (HBp-3 and Lp-2) for binding recognition at benzodiazepine (Bzs) site of GABA(A) receptors (GABA(A)-Rs). In this work ADLR method is used to rationalize the affinity data of 23 new compounds and to improve the knowledge on HBp-3 area, hydrogen bond area. Among these new compounds emerge the pyrrolo derivatives (18, 25, 28, 34, and 37) for their good affinity value (14.9 > K-i(nM) > 63.0). In the orientations proposed by ADLR, the NH moiety of the pyrrole ring, independently of the position in the pyrazolobenzotriazine core, fits in HBp-3 area and points out the acceptor feature of this hydrogen bond area, already known as donor area. Unexpectedly, the oxygen atom of the furane ring does not form efficient hydrogen bond with the same area, probably for an imperfect distance. The size of substituent at position 8 is important but not necessary for the receptor recognition, in fact the interdependence between the features of the 3- and 8-substituent's is again verified, (i.e., compound 20 vs 32). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.009

文献信息

• New 3-, 8-disubstituted pyrazolo[5,1-c][1,2,4]benzotriazines useful for studying the interaction with the HBp-3 area (hydrogen bond point area) in the benzodiazepine site on the γ-aminobutyric acid type A (GABAA) receptor
  作者：Gabriella Guerrini、Giovanna Ciciani、Fabrizio Bruni、Silvia Selleri、Fabrizio Melani、Simona Daniele、Claudia Martini、Annarella Costanzo

  DOI：10.1016/j.bmc.2011.04.009

  日期：2011.5

  The pharmacophoric model using ADLR procedure, based on pyrazolo[5,1-c][1,2,4]benzotriazine system, studied in our laboratory, allowed us to identify the essential interaction points (HBp-1, HBp-2, and Lp-1) and the important areas for affinity modulation (HBp-3 and Lp-2) for binding recognition at benzodiazepine (Bzs) site of GABA(A) receptors (GABA(A)-Rs). In this work ADLR method is used to rationalize the affinity data of 23 new compounds and to improve the knowledge on HBp-3 area, hydrogen bond area. Among these new compounds emerge the pyrrolo derivatives (18, 25, 28, 34, and 37) for their good affinity value (14.9 > K-i(nM) > 63.0). In the orientations proposed by ADLR, the NH moiety of the pyrrole ring, independently of the position in the pyrazolobenzotriazine core, fits in HBp-3 area and points out the acceptor feature of this hydrogen bond area, already known as donor area. Unexpectedly, the oxygen atom of the furane ring does not form efficient hydrogen bond with the same area, probably for an imperfect distance. The size of substituent at position 8 is important but not necessary for the receptor recognition, in fact the interdependence between the features of the 3- and 8-substituent's is again verified, (i.e., compound 20 vs 32). (C) 2011 Elsevier Ltd. All rights reserved.