1-(2-chlorophenyl)-3-isoquinolinecarboxylic acid chloride | 109960-06-7

• 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)-3-isoquinolinecarboxylic acid chloride
• 英文别名: 1-(2-chlorophenyl)isoquinoline-3-carboxylic acid chloride；1-(2-Chlorophenyl)isoquinoline-3-carbonyl chloride
• CAS: 109960-06-7
• 化学式: C₁₆H₉Cl₂NO
• 分子量: 302.16
• InChiKey: BAOLORZGPRXDIP-UHFFFAOYSA-N

物化性质

• 沸点：
  426.8±40.0 °C(Predicted)
• 密度：
  1.370±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(2-chlorophenyl)-3-isoquinolinecarboxylic acid chloride 在 碘代三甲硅烷 、 碳酸氢钠 作用下， 以 氯仿 、 水 、 乙腈 为溶剂， 反应 1.17h， 生成 (S)-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
• 作为产物：
  描述：

  1-(2-氯苯基)异喹啉-3-羧酸 在 草酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 1-(2-chlorophenyl)-3-isoquinolinecarboxylic acid chloride
  参考文献：
  名称：

  的合成Ñ甲基ñ - （1-甲基丙基）-1-（2-氯苯基）异喹啉-3- [ 11 C]甲酰胺（[ 11 C-羰基] PK11195），并使用[一些类似物11 C]一氧化碳和1-（2-氯苯基）异喹啉-3-基三氟甲磺酸酯

  摘要：

  这 苯二氮卓 受体 配体， N-甲基-N-（1-甲基丙基）-1-（2-氯苯基）异喹啉-3-羧酰胺（PK11195），以及五个结构上相关的类似物进行了11 C标记通过一个钯[ 11 C]一氧化碳介导的羰基化反应，1-（2-氯苯基）异喹啉-3-基三氟甲磺酸盐 和各种 胺类。该11具有在10-55％的范围内衰变校正的放射化学产率和具有高比放射性得到C标记的产品（例如200-900吉贝微摩尔-1）。最终产物的放射化学纯度超过98％。在以3.75 GBq [ 11 C]一氧化碳开始的典型实验中，羰基化反应开始后35分钟内获得了0.57 GBq的LC纯化产物。为了确认标记位置，制备了N-（1-甲基乙基）-1-（2-氯苯基）-异喹啉-3-（13 C）甲酰胺，并通过以下方法进行了分析。核磁共振。前体1-（2-氯苯基）异喹啉-3-基三氟甲磺酸盐 从五步开始合成 2-氯二苯甲酮。前体N-甲基仲丁胺 从准备 仲丁胺

  DOI：

  10.1039/b205838c

文献信息

• Synthesis of N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-[¹¹C]carboxamide ([¹¹C-carbonyl]PK11195) and some analogues using [¹¹C]carbon monoxide and 1-(2-chlorophenyl)isoquinolin-3-yl triflate
  作者：Obaidur Rahman、Tor Kihlberg、Bengt Långström

  DOI：10.1039/b205838c

  日期：——

  using [11C]carbon monoxide, 1-(2-chlorophenyl)isoquinolin-3-yl trifluoromethanesulfonate and various amines. The 11C-labelled products were obtained with decay-corrected radiochemical yields in the range of 10–55% and with high specific radioactivity (e.g. 200–900 GBq µmol−1). The radiochemical purity of the final products exceeded 98%. In a typical experiment starting with 3.75 GBq [11C]carbon monoxide

  这 苯二氮卓 受体 配体， N-甲基-N-（1-甲基丙基）-1-（2-氯苯基）异喹啉-3-羧酰胺（PK11195），以及五个结构上相关的类似物进行了11 C标记通过一个钯[ 11 C]一氧化碳介导的羰基化反应，1-（2-氯苯基）异喹啉-3-基三氟甲磺酸盐 和各种 胺类。该11具有在10-55％的范围内衰变校正的放射化学产率和具有高比放射性得到C标记的产品（例如200-900吉贝微摩尔-1）。最终产物的放射化学纯度超过98％。在以3.75 GBq [ 11 C]一氧化碳开始的典型实验中，羰基化反应开始后35分钟内获得了0.57 GBq的LC纯化产物。为了确认标记位置，制备了N-（1-甲基乙基）-1-（2-氯苯基）-异喹啉-3-（13 C）甲酰胺，并通过以下方法进行了分析。核磁共振。前体1-（2-氯苯基）异喹啉-3-基三氟甲磺酸盐 从五步开始合成 2-氯二苯甲酮。前体N-甲基仲丁胺 从准备 仲丁胺
• 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.
• 1-(Phenyl)isoquinoline carboxamides: a novel class of subtype selective inhibitors of thyrotropin-releasing hormone (TRH) receptors
  作者：Jian-kang Jiang、Craig J. Thomas、Susanne Neumann、Xinping Lu、Kenner C. Rice、Marvin C. Gershengorn

  DOI：10.1016/j.bmcl.2004.11.017

  日期：2005.2

  We report the synthesis of and binding to the two subtypes of mouse thyrotropin-releasing hormone (TRH) receptors, TRH-R1 and TRH-R2, of several 1-(phenyl)isoquinoline carboxamide analogues. These analogues showed a degree of selectivity for binding at TRH-R2. These are the first ligands reported that show selective binding to these receptors.

  我们报告了几种1-（苯基）异喹啉羧酰胺类似物的小鼠促甲状腺激素释放激素（TRH）受体TRH-R1和TRH-R2的两个亚型的合成和结合。这些类似物显示出一定程度的结合TRH-R2的选择性。这些是报道的第一批对这些受体具有选择性结合的配体。