tert-butyl 2-(4-isopropylpiperazine-1-carbonyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate | 1539278-05-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 2-(4-isopropylpiperazine-1-carbonyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate
• CAS: 1539278-05-1
• 化学式: C₂₀H₃₆N₄O₃
• 分子量: 380.531
• InChiKey: GYSXYWMKSAFDGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.47
• 重原子数：
  27.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  56.33
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(4-isopropylpiperazine-1-carbonyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 (4-isopropylpiperazin-1-yl)(2,7-diazaspiro[3.5]nonan-2-yl)methanone
  参考文献：
  名称：

  Discovery of Spirofused Piperazine and Diazepane Amides as Selective Histamine-3 Antagonists with in Vivo Efficacy in a Mouse Model of Cognition

  摘要：

  A new series of potent and selective histamine-3 receptor (H3R) antagonists was identified on the basis of an azaspiro[2.5]octane carboxamide scaffold. Many scaffold modifications were largely tolerated, resulting in nanomolar-potent compounds in the H3R functional assay. Exemplar compound 6s demonstrated a selective profile against a panel of 144 secondary pharmacological receptors, with activity at only sigma 2 (62% at 10 mu M). Compound 6s demonstrated free-plasma exposures above the IC50 (similar to 50x) with a brain-to-plasma ratio of similar to 3 following intravenous dosing in mice. At three doses tested in the mouse novel object recognition model (1, 3, and 10 mg/kg s.c.), 6s demonstrated a statistically significant response compared with the control group. This series represents a new scaffold of H-3 receptor antagonists that demonstrates in vivo exposure and efficacy in an animal model of cognition.

  DOI：

  10.1021/jm4014828
• 作为产物：
  描述：

  1-异丙基哌嗪 、 2,7-二氮杂螺[3.5]壬烷-7-羧酸叔丁酯盐酸盐 、 对硝基苯基氯甲酸酯 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 12.08h， 以72%的产率得到tert-butyl 2-(4-isopropylpiperazine-1-carbonyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate
  参考文献：
  名称：

  Discovery of Spirofused Piperazine and Diazepane Amides as Selective Histamine-3 Antagonists with in Vivo Efficacy in a Mouse Model of Cognition

  摘要：

  A new series of potent and selective histamine-3 receptor (H3R) antagonists was identified on the basis of an azaspiro[2.5]octane carboxamide scaffold. Many scaffold modifications were largely tolerated, resulting in nanomolar-potent compounds in the H3R functional assay. Exemplar compound 6s demonstrated a selective profile against a panel of 144 secondary pharmacological receptors, with activity at only sigma 2 (62% at 10 mu M). Compound 6s demonstrated free-plasma exposures above the IC50 (similar to 50x) with a brain-to-plasma ratio of similar to 3 following intravenous dosing in mice. At three doses tested in the mouse novel object recognition model (1, 3, and 10 mg/kg s.c.), 6s demonstrated a statistically significant response compared with the control group. This series represents a new scaffold of H-3 receptor antagonists that demonstrates in vivo exposure and efficacy in an animal model of cognition.

  DOI：

  10.1021/jm4014828