6-hydroxy-3-(4-methoxyphenyl)-1,2,4-triazolo[3,4-a]phthalazine | 87540-94-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-hydroxy-3-(4-methoxyphenyl)-1,2,4-triazolo[3,4-a]phthalazine
• 英文别名: 3-(4-methoxyphenyl)-5H-[1,2,4]triazolo[3,4-a]phthalazin-6-one
• CAS: 87540-94-1
• 化学式: C₁₆H₁₂N₄O₂
• 分子量: 292.297
• InChiKey: IJIKKYUDVPQLGL-UHFFFAOYSA-N

物化性质

• 熔点：
  307-309 °C(Solv: chloroform (67-66-3))
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  69
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-溴-2-吡咯啉酮 、 6-hydroxy-3-(4-methoxyphenyl)-1,2,4-triazolo[3,4-a]phthalazine 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 以82%的产率得到3-[[3-(4-methoxyphenyl)-1,2,4-triazolo[3,4-a]phthalazin-6-yl]oxy]-2-pyrrolidinone
  参考文献：
  名称：

  6-substituted-s-triazolo[3,4-a]phthalazine derivatives

  摘要：

  本发明涉及新的s-三唑并[3,4-a]酞嗪衍生物，涉及它们的制备方法以及含有它们的药物组合物。

  公开号：

  US04788186A1
• 作为产物：
  描述：

  1-chloro-4-hydrazinophthalazine 在 sodium 作用下， 反应 8.25h， 生成 6-hydroxy-3-(4-methoxyphenyl)-1,2,4-triazolo[3,4-a]phthalazine
  参考文献：
  名称：

  Tarzia; Occelli; Corsico, Farmaco, Edizione Scientifica, 1988, vol. 43, # 2, p. 189 - 201

  摘要：

  DOI：

文献信息

• 3-Phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-<i>a</i>]phthalazines and Analogues:  High-Affinity γ-Aminobutyric Acid-A Benzodiazepine Receptor Ligands with α2, α3, and α5-Subtype Binding Selectivity over α1
  作者：Robert W. Carling、Kevin W. Moore、Leslie J. Street、Deborah Wild、Catherine Isted、Paul D. Leeson、Steven Thomas、Desmond O'Connor、Ruth M. McKernan、Katherine Quirk、Susan M. Cook、John R. Atack、Keith A. Wafford、Sally A. Thompson、Gerard R. Dawson、Pushpinder Ferris、José L. Castro

  DOI：10.1021/jm031020p

  日期：2004.3.1

  Studies with our screening lead 5 and the literature compound 6 led to the identification of 6-benzyloxy-3-(4-methoxy)phenyl-1,2,4-triazolo[3,4-a]phthalazine 8 as a ligand with binding selectivity for the gamma-aminobutyric acid-A (GABA-A) alpha3- and alpha5-containing receptor subtypes over the GABA-A alpha1 subtype (K-i: alpha2 = 850 nM, alpha3 = 170 nM, alpha5 = 72 nM, alpha1 = 1400 nM). Early optimization studies identified the close analogue 10 (Ki: alpha2 = 16 nM, alpha3 = 41 nM, alpha5 = 38 nM, alpha1 = 280 nM) as a suitable lead for further study. High-affinity ligands were identified by replacing the 6-benzyloxy group of compound 10 with 2-pyridylmethoxy (compound 29), but binding selectivity was not enhanced (K-i: alpha2 = 1.7 nM, alpha3 = 0.71 nM, alpha5 = 0.33 nM, alpha1 = 2.7 nM). Furthermore, on evaluation in xenopus oocytes,(22) 29 was discovered to be a weak to moderate inverse agonist at all four receptor subtypes (alpha1, -7%; alpha2, -5%; alpha3, -16%; alpha5, -5%). Replacement of the 3-phenyl group of 29 with alternatives led to reduced affinity, and smaller 3-substituents led to reduced efficacy. Methyl substitution of the benzo-fused ring of 29 at the 7-, 8-, and 10-positions resulted in increased efficacy although selectivity was abolished. Increased efficacy and retention of selectivity for alpha3 over alpha1 was achieved with the 7,8,9,10-tetrahydro-(7,10-ethano)-phthalazine 62. Compound 62 is currently one of the most binding selective GABA-A alpha3-benzodiazepine-site partial agonists known, and although its selectivity is limited, its good pharmacokinetic profile in the rat (33% oral bioavailability after a 3 mg/kg dose, reaching a peak plasma concentration of 179 ng/mL; half-life of I h) made it a useful pharmacological tool to explore the effect of a GABA-A alpha2/alpha3 agonist in vivo.
• TARZIA, G.;OCCELLI, E.;CORSICO, N.;LUZZANI, F.;BARONE, D., FRAMACO. ED. SCI., 43,(1988) N 2, C. 189-201
  作者：TARZIA, G.、OCCELLI, E.、CORSICO, N.、LUZZANI, F.、BARONE, D.

  DOI：——

  日期：——
• New 6-substituted-s-triazolo(3,4-a)phthalazine derivatives
  申请人：GRUPPO LEPETIT S.P.A.

  公开号：EP0085840B1

  公开（公告）日：1986-10-01
• US4788186A
  申请人：——

  公开号：US4788186A

  公开（公告）日：1988-11-29
• 6-substituted-s-triazolo[3,4-a]phthalazine derivatives
  申请人：Gruppo Lepetit S.p.A.

  公开号：US04788186A1

  公开（公告）日：1988-11-29

  The present invention refers to new s-triazolo[3,4-a]phthalazine derivatives, to the process for their preparation and to the pharmaceutical compositions containing them.

  本发明涉及新的s-三唑并[3,4-a]酞嗪衍生物，涉及它们的制备方法以及含有它们的药物组合物。