1-(4-fluorophenyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5-(2-methyl-2H-tetrazol-5-yl)-1H-indole | 243467-20-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-(4-fluorophenyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5-(2-methyl-2H-tetrazol-5-yl)-1H-indole
• 英文别名: 1-(4-fluorophenyl)-3-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-5-(2-methyltetrazol-5-yl)indole
• CAS: 243467-20-1
• 化学式: C₂₂H₂₁FN₆
• 分子量: 388.447
• InChiKey: YJLHCZXTIBFARI-UHFFFAOYSA-N

物化性质

• 沸点：
  526.1±60.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5-(2-methyl-2H-tetrazol-5-yl)-1H-indole 在 platinum(IV) oxide 、 氢气 作用下， 以 溶剂黄146 为溶剂， 20.0 ℃ 、300.01 kPa 条件下， 反应 10.0h， 以16%的产率得到1-(4-fluorophenyl)-3-(1-methyl-4-piperidinyl)-5-(2-methyltetrazol-5-yl)-1H-indole
  参考文献：
  名称：

  Discovery of novel α1-adrenoceptor ligands based on the antipsychotic sertindole suitable for labeling as PET ligands

  摘要：

  The synthesis and in vitro preclinical profile of a series of 5-heteroaryl substituted analogs of the antipsychotic drug sertindole are presented. Compounds 1-(4-fluorophenyl)-3-(1-methylpiperidin-4-yl)-5-(pyrimidin-5-yl)-1H-indole (Lu AA27122, 3i) and 1-(4-fluorophenyl)-5-(1-methyl-1H-1,2,4-triazol-3-yl)-3-(1-methylpiperidin-4-yl)-1H-indole (3l) were identified as high affinity alpha(1A)-adrenoceptor ligands with K-i values of 0.52 and 0.16 nM, respectively, and with a >100-fold selectivity versus dopamine D-2 receptors. Compound 3i showed almost equal affinity for alpha(1B)- (K-i = 1.9 nM) and alpha(1D)-adrenoceptors (K-i = 2.5 nM) as for alpha(1A), as well as moderate affinity for 5-HT1B (K-i = 13 nM) and 5-HT6 (K-i = 16 nM) receptors, whereas 3l showed >40-fold selectivity toward all other targets tested. Based on in vitro assays for assessment of permeability rates and extent, it is predicted that both compounds enter the brain of rats, non-human primates, as well as humans, and as such are good candidates to be carried forward for further evaluation as positron emission tomography (PET) ligands. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.10.049
• 作为产物：
  描述：

  1H-吲哚-5-甲腈,1-(4-氟苯基)- 在 N-甲基吡咯烷酮 、 sodium azide 、 potassium tert-butylate 、 三乙胺盐酸盐 作用下， 以 乙二醇二甲醚 、 丙酮 、 三氟乙酸 为溶剂， 反应 3.5h， 生成 1-(4-fluorophenyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5-(2-methyl-2H-tetrazol-5-yl)-1H-indole
  参考文献：
  名称：

  Discovery of novel α1-adrenoceptor ligands based on the antipsychotic sertindole suitable for labeling as PET ligands

  摘要：

  The synthesis and in vitro preclinical profile of a series of 5-heteroaryl substituted analogs of the antipsychotic drug sertindole are presented. Compounds 1-(4-fluorophenyl)-3-(1-methylpiperidin-4-yl)-5-(pyrimidin-5-yl)-1H-indole (Lu AA27122, 3i) and 1-(4-fluorophenyl)-5-(1-methyl-1H-1,2,4-triazol-3-yl)-3-(1-methylpiperidin-4-yl)-1H-indole (3l) were identified as high affinity alpha(1A)-adrenoceptor ligands with K-i values of 0.52 and 0.16 nM, respectively, and with a >100-fold selectivity versus dopamine D-2 receptors. Compound 3i showed almost equal affinity for alpha(1B)- (K-i = 1.9 nM) and alpha(1D)-adrenoceptors (K-i = 2.5 nM) as for alpha(1A), as well as moderate affinity for 5-HT1B (K-i = 13 nM) and 5-HT6 (K-i = 16 nM) receptors, whereas 3l showed >40-fold selectivity toward all other targets tested. Based on in vitro assays for assessment of permeability rates and extent, it is predicted that both compounds enter the brain of rats, non-human primates, as well as humans, and as such are good candidates to be carried forward for further evaluation as positron emission tomography (PET) ligands. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.10.049

文献信息

• Discovery of novel α1-adrenoceptor ligands based on the antipsychotic sertindole suitable for labeling as PET ligands
  作者：Morten Jørgensen、Pernille N. Jørgensen、Claus T. Christoffersen、Klaus G. Jensen、Thomas Balle、Benny Bang-Andersen

  DOI：10.1016/j.bmc.2012.10.049

  日期：2013.1

  The synthesis and in vitro preclinical profile of a series of 5-heteroaryl substituted analogs of the antipsychotic drug sertindole are presented. Compounds 1-(4-fluorophenyl)-3-(1-methylpiperidin-4-yl)-5-(pyrimidin-5-yl)-1H-indole (Lu AA27122, 3i) and 1-(4-fluorophenyl)-5-(1-methyl-1H-1,2,4-triazol-3-yl)-3-(1-methylpiperidin-4-yl)-1H-indole (3l) were identified as high affinity alpha(1A)-adrenoceptor ligands with K-i values of 0.52 and 0.16 nM, respectively, and with a >100-fold selectivity versus dopamine D-2 receptors. Compound 3i showed almost equal affinity for alpha(1B)- (K-i = 1.9 nM) and alpha(1D)-adrenoceptors (K-i = 2.5 nM) as for alpha(1A), as well as moderate affinity for 5-HT1B (K-i = 13 nM) and 5-HT6 (K-i = 16 nM) receptors, whereas 3l showed >40-fold selectivity toward all other targets tested. Based on in vitro assays for assessment of permeability rates and extent, it is predicted that both compounds enter the brain of rats, non-human primates, as well as humans, and as such are good candidates to be carried forward for further evaluation as positron emission tomography (PET) ligands. (C) 2012 Elsevier Ltd. All rights reserved.