(+/-)-1-(2-chlorophenyl)-N-(1-methylpropyl)-N-(2-aminoethyl)-3-isoquinolinecarboxamide | 109960-11-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (+/-)-1-(2-chlorophenyl)-N-(1-methylpropyl)-N-(2-aminoethyl)-3-isoquinolinecarboxamide
• 英文别名: N-(2-aminoethyl)-1-(2-chlorophenyl)-N-sec-butyl-isoquinoline-3-carboxamide；N-(2-aminoethyl)-N-butan-2-yl-1-(2-chlorophenyl)isoquinoline-3-carboxamide
• CAS: 109960-11-4
• 化学式: C₂₂H₂₄ClN₃O
• 分子量: 381.905
• InChiKey: AWSPPPGCMKCOEW-UHFFFAOYSA-N

物化性质

• 沸点：
  559.6±50.0 °C(Predicted)
• 密度：
  1.195±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-1-(2-chlorophenyl)-N-(1-methylpropyl)-N-(2-aminoethyl)-3-isoquinolinecarboxamide 、 硫光气 以86%的产率得到
  参考文献：
  名称：

  NEWMAN, AMY HAUCK;LUEDDENS, HARTMUT W. M.;SKOLNICK, PHIL;RICE, KENNER C., J. MED. CHEM., 30,(1987) N 10, 1901-1905

  摘要：

  DOI：
• 作为产物：
  描述：

  1-(2-氯苯基)异喹啉-3-羧酸 在 磺酰氯 、 碘代三甲硅烷 、 碳酸氢钠 作用下， 以 氯仿 、 水 、 乙腈 为溶剂， 反应 4.17h， 生成 (+/-)-1-(2-chlorophenyl)-N-(1-methylpropyl)-N-(2-aminoethyl)-3-isoquinolinecarboxamide
  参考文献：
  名称：

  Novel irreversible ligands specific for "peripheral" type benzodiazepine receptors: (.+-.)-, (+)- and (-)-1-(2-chlorophenyl)-N-(1-methylpropyl)-N-(2-isothiocyanatoethyl)-3-isoquinolinecarboxamide and 1-(2-isothiocyanatoethyl)-7-chloro-1,3-dihydro-5-(4-chlorophenyl)-2H-1,4-benzodiazepin-2-one

  摘要：

  Novel ligands that bind irreversibly and selectively to "peripheral" type benzodiazepine receptors (PBR) have been prepared. These compounds inhibit radiolabeled binding to PBR in the nanomolar range. The 2-isothiocyanatoethyl analogue of Ro 5-4864 (1-methyl-7-chloro-1,3-dihydro-5-(4-chlorophenyl)-2H-1,4-benzodiazepi n-2-one) (5, AHN 086) was synthesized in three steps from desmethyl Ro 5-4864. The (+/-) (11a, AHN 070), R-(-) (11b), and S-(+) (11c) 2-isothiocyanatoethyl derivatives of PK 11195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxami de) were each prepared in three steps from PK 11209 (1-(2-chlorophenyl)-3-isoquinolinecarboxylic acid, 6). All four compounds inhibited radioligand binding to the PBR in brain and kidney. The R-(-) stereoisomer 11b was observed to be approximately 2.5-fold more potent than its enantiomer 11c; this is the first report of stereoselectivity in the isoquinoline series of ligands selective for the PBR. Furthermore, pH dependency studies showed that, at lower pH, change in the affinities for the PBR ligands is a property of the receptor, substantiating the hypothesis that a histidine moiety on the PBR is the most likely site for covalent bond formation, whereas, at higher pH, the observed changes in affinities can be attributed to properties of the compounds. All four of these novel ligands are potentially useful tools in the investigation of the PBR.

  DOI：

  10.1021/jm00393a036

文献信息

• NEWMAN, AMY HAUCK;LUEDDENS, HARTMUT W. M.;SKOLNICK, PHIL;RICE, KENNER C., J. MED. CHEM., 30,(1987) N 10, 1901-1905
  作者：NEWMAN, AMY HAUCK、LUEDDENS, HARTMUT W. M.、SKOLNICK, PHIL、RICE, KENNER C.

  DOI：——

  日期：——
• Novel irreversible ligands specific for "peripheral" type benzodiazepine receptors: (.+-.)-, (+)- and (-)-1-(2-chlorophenyl)-N-(1-methylpropyl)-N-(2-isothiocyanatoethyl)-3-isoquinolinecarboxamide and 1-(2-isothiocyanatoethyl)-7-chloro-1,3-dihydro-5-(4-chlorophenyl)-2H-1,4-benzodiazepin-2-one
  作者：Amy Hauck Newman、Hartmut W. M. Lueddens、Phil Skolnick、Kenner C. Rice

  DOI：10.1021/jm00393a036

  日期：1987.10

  Novel ligands that bind irreversibly and selectively to "peripheral" type benzodiazepine receptors (PBR) have been prepared. These compounds inhibit radiolabeled binding to PBR in the nanomolar range. The 2-isothiocyanatoethyl analogue of Ro 5-4864 (1-methyl-7-chloro-1,3-dihydro-5-(4-chlorophenyl)-2H-1,4-benzodiazepi n-2-one) (5, AHN 086) was synthesized in three steps from desmethyl Ro 5-4864. The (+/-) (11a, AHN 070), R-(-) (11b), and S-(+) (11c) 2-isothiocyanatoethyl derivatives of PK 11195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxami de) were each prepared in three steps from PK 11209 (1-(2-chlorophenyl)-3-isoquinolinecarboxylic acid, 6). All four compounds inhibited radioligand binding to the PBR in brain and kidney. The R-(-) stereoisomer 11b was observed to be approximately 2.5-fold more potent than its enantiomer 11c; this is the first report of stereoselectivity in the isoquinoline series of ligands selective for the PBR. Furthermore, pH dependency studies showed that, at lower pH, change in the affinities for the PBR ligands is a property of the receptor, substantiating the hypothesis that a histidine moiety on the PBR is the most likely site for covalent bond formation, whereas, at higher pH, the observed changes in affinities can be attributed to properties of the compounds. All four of these novel ligands are potentially useful tools in the investigation of the PBR.