[2-(trifluoromethyl)-8,9-dihydrofuro[3,2-c]pyrazolo[1,5-a]pyridin-1-yl]methanol | 1031849-29-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: [2-(trifluoromethyl)-8,9-dihydrofuro[3,2-c]pyrazolo[1,5-a]pyridin-1-yl]methanol
• 英文别名: [4-(Trifluoromethyl)-10-oxa-5,6-diazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7-tetraen-3-yl]methanol
• CAS: 1031849-29-2
• 化学式: C₁₁H₉F₃N₂O₂
• 分子量: 258.2
• InChiKey: GTTAIHNSLBDTIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  46.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [2-(trifluoromethyl)-8,9-dihydrofuro[3,2-c]pyrazolo[1,5-a]pyridin-1-yl]methanol 在 三氟化硼乙醚 、 氨 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 2-[2-(trifluoromethyl)-8,9-dihydrofuro[3,2-c]pyrazolo[1,5-a]pyridin-1-yl]ethanamine
  参考文献：
  名称：

  Synthesis of a Novel Series of Tricyclic Dihydrofuran Derivatives: Discovery of 8,9-Dihydrofuro[3,2-c]pyrazolo[1,5-a]pyridines as Melatonin Receptor (MT₁/MT₂) Ligands

  摘要：

  Novel tricyclic dihydrofuran derivatives were designed, synthesized, and evaluated as melatonin receptor (MT1/MT2) ligands based on the previously reported 1,6-dihydro-2H-indeno[5,4-b]furan la. By screening the central tricyclic cores, we identified 8,9-dihydrofuro [3,2-c]pyrazolo [1,5-a]pyridine as a potent scaffold with a high ligand-lipophilicity efficiency (LLE) value. Subsequent optimization of the side chains led to identification of the potent MT1/MT2 agonist 4d (MT1, K-i = 0.062 nM; MT2, K-i = 0.420 nM) with good oral absorption and blood-brain barrier (BBB) penetration in rats. The oral administration of compound 4d exhibited a sleep-promoting action in freely moving cats at 0.1 mg/kg.

  DOI：

  10.1021/jm200385u
• 作为产物：
  描述：

  ethyl 2-(trifluoromethyl)-8,9-dihydrofuro[3,2-c]pyrazolo-[1,5-a]pyridine-1-carboxylate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以49%的产率得到[2-(trifluoromethyl)-8,9-dihydrofuro[3,2-c]pyrazolo[1,5-a]pyridin-1-yl]methanol
  参考文献：
  名称：

  Synthesis of a Novel Series of Tricyclic Dihydrofuran Derivatives: Discovery of 8,9-Dihydrofuro[3,2-c]pyrazolo[1,5-a]pyridines as Melatonin Receptor (MT₁/MT₂) Ligands

  摘要：

  Novel tricyclic dihydrofuran derivatives were designed, synthesized, and evaluated as melatonin receptor (MT1/MT2) ligands based on the previously reported 1,6-dihydro-2H-indeno[5,4-b]furan la. By screening the central tricyclic cores, we identified 8,9-dihydrofuro [3,2-c]pyrazolo [1,5-a]pyridine as a potent scaffold with a high ligand-lipophilicity efficiency (LLE) value. Subsequent optimization of the side chains led to identification of the potent MT1/MT2 agonist 4d (MT1, K-i = 0.062 nM; MT2, K-i = 0.420 nM) with good oral absorption and blood-brain barrier (BBB) penetration in rats. The oral administration of compound 4d exhibited a sleep-promoting action in freely moving cats at 0.1 mg/kg.

  DOI：

  10.1021/jm200385u

文献信息

• TRICYCLIC COMPOUND AND MEDICAL USE THEREOF
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2100895B1

  公开（公告）日：2012-03-07
• US8273761B2
  申请人：——

  公开号：US8273761B2

  公开（公告）日：2012-09-25
• Synthesis of a Novel Series of Tricyclic Dihydrofuran Derivatives: Discovery of 8,9-Dihydrofuro[3,2-<i>c</i>]pyrazolo[1,5-<i>a</i>]pyridines as Melatonin Receptor (MT₁/MT₂) Ligands
  作者：Tatsuki Koike、Takafumi Takai、Yasutaka Hoashi、Masaharu Nakayama、Yohei Kosugi、Masato Nakashima、Shin-ichi Yoshikubo、Keisuke Hirai、Osamu Uchikawa

  DOI：10.1021/jm200385u

  日期：2011.6.23

  Novel tricyclic dihydrofuran derivatives were designed, synthesized, and evaluated as melatonin receptor (MT1/MT2) ligands based on the previously reported 1,6-dihydro-2H-indeno[5,4-b]furan la. By screening the central tricyclic cores, we identified 8,9-dihydrofuro [3,2-c]pyrazolo [1,5-a]pyridine as a potent scaffold with a high ligand-lipophilicity efficiency (LLE) value. Subsequent optimization of the side chains led to identification of the potent MT1/MT2 agonist 4d (MT1, K-i = 0.062 nM; MT2, K-i = 0.420 nM) with good oral absorption and blood-brain barrier (BBB) penetration in rats. The oral administration of compound 4d exhibited a sleep-promoting action in freely moving cats at 0.1 mg/kg.