8-hydroxy-4-methyl-2,3,5,6-tetrahydro-(1H)-benzo[c]quinolizin-3-one | 736155-95-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 8-hydroxy-4-methyl-2,3,5,6-tetrahydro-(1H)-benzo[c]quinolizin-3-one
• 英文别名: 8-Hydroxy-4-methyl-1,2,5,6-tetrahydrobenzo[f]quinolizin-3-one
• CAS: 736155-95-6
• 化学式: C₁₄H₁₅NO₂
• 分子量: 229.279
• InChiKey: FFAQXLJVEGGTEG-UHFFFAOYSA-N

物化性质

• 沸点：
  429.1±45.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-氯苄溴 、 8-hydroxy-4-methyl-2,3,5,6-tetrahydro-(1H)-benzo[c]quinolizin-3-one 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 6.0h， 以38%的产率得到8-(4-Chloro-benzyloxy)-4-methyl-1,2,5,6-tetrahydro-pyrido[1,2-a]quinolin-3-one
  参考文献：
  名称：

  Synthesis, Biological Activity, and Three-Dimensional Quantitative Structure−Activity Relationship Model for a Series of Benzo[c]quinolizin-3-ones, Nonsteroidal Inhibitors of Human Steroid 5α-Reductase 1

  摘要：

  New 5alpha-reductase 1 (5alphaR-1) inhibitors were designed to complete a consistent set of analogues suitable for a 3D QSAR study. These compounds were synthesized by a modification of the aza-Robinson annulation, further functionalized by Pd-catalyzed cross-coupling processes, and were tested with human 5alphaR-1 expressed in Chinese hamster ovary 1827 cells. It turned out that the potency of the resulting inhibitors was strongly dependent on the type of substitution at the 8 position, with the IC50 values ranging from 8.1 to 1050 nM. The construction of this homogeneous set of molecules allowed a 3D QSAR study. In particular, comparative molecular field analysis (CoMFA) was used to correlate the potency of the inhibitors with their physicochemical features. Highly accurate evaluations of the atomic point charges were carried out by means of quantum chemical calculations at the DFT/B3LYP level of theory followed by the RESP fitting procedure. It turned out that increasing the reliability of electrostatic parameters greatly affected the statistical results of the QSAR analysis. The 3D QSAR model proposed could be very useful in the further development of 5alphaR-1 inhibitors, which are suitable candidates to be evaluated as drugs in the treatment of 5alphaR-1 related diseases such as acne and alopecia in men and hirsutism in women.

  DOI：

  10.1021/jm031131o
• 作为产物：
  描述：

  6-羟基-3,4-二氢-2(1H)-喹诺酮 在 劳森试剂 、 咪唑 、 18-冠醚-6 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 5.41h， 生成 8-hydroxy-4-methyl-2,3,5,6-tetrahydro-(1H)-benzo[c]quinolizin-3-one
  参考文献：
  名称：

  Synthesis, Biological Activity, and Three-Dimensional Quantitative Structure−Activity Relationship Model for a Series of Benzo[c]quinolizin-3-ones, Nonsteroidal Inhibitors of Human Steroid 5α-Reductase 1

  摘要：

  New 5alpha-reductase 1 (5alphaR-1) inhibitors were designed to complete a consistent set of analogues suitable for a 3D QSAR study. These compounds were synthesized by a modification of the aza-Robinson annulation, further functionalized by Pd-catalyzed cross-coupling processes, and were tested with human 5alphaR-1 expressed in Chinese hamster ovary 1827 cells. It turned out that the potency of the resulting inhibitors was strongly dependent on the type of substitution at the 8 position, with the IC50 values ranging from 8.1 to 1050 nM. The construction of this homogeneous set of molecules allowed a 3D QSAR study. In particular, comparative molecular field analysis (CoMFA) was used to correlate the potency of the inhibitors with their physicochemical features. Highly accurate evaluations of the atomic point charges were carried out by means of quantum chemical calculations at the DFT/B3LYP level of theory followed by the RESP fitting procedure. It turned out that increasing the reliability of electrostatic parameters greatly affected the statistical results of the QSAR analysis. The 3D QSAR model proposed could be very useful in the further development of 5alphaR-1 inhibitors, which are suitable candidates to be evaluated as drugs in the treatment of 5alphaR-1 related diseases such as acne and alopecia in men and hirsutism in women.

  DOI：

  10.1021/jm031131o