methyl 6-chloro-2-[4-(methylsulfonyl)benzyl]-1-oxo-4-{[(trifluoromethyl)sulfonyl]oxy}-1,2-dihydroisoquinoline-3-carboxylate | 583837-82-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: methyl 6-chloro-2-[4-(methylsulfonyl)benzyl]-1-oxo-4-{[(trifluoromethyl)sulfonyl]oxy}-1,2-dihydroisoquinoline-3-carboxylate
• 英文别名: 6-chloro-2-(4-methanesulfonylbenzyl)-1-oxo-4-trifluoromethanesulfonyloxy-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester；6-Chloro-2-(4-methanesulfonylbenzyl)-1-oxo-4-trifluoromethanesulfonyloxy-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester；methyl 6-chloro-2-[(4-methylsulfonylphenyl)methyl]-1-oxo-4-(trifluoromethylsulfonyloxy)isoquinoline-3-carboxylate
• CAS: 583837-82-5
• 化学式: C₂₀H₁₅ClF₃NO₈S₂
• 分子量: 553.921
• InChiKey: JIULVWOZXVZMEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  141
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  methyl 6-chloro-2-[4-(methylsulfonyl)benzyl]-1-oxo-4-{[(trifluoromethyl)sulfonyl]oxy}-1,2-dihydroisoquinoline-3-carboxylate 、 4-甲酰基苯硼酸 生成 methyl 6-chloro-4-(4-formylphenyl)-2-[4-(methylsulfonyl)benzyl]-1-oxo-1,2-dihydroisoquinoline-3-carboxylate
  参考文献：
  名称：

  Jnk inhibitor

  摘要：

  含有异喹啉酮骨架或其盐的JNK抑制剂，例如由以下式表示的化合物：其中环A和环B均为可选取代的苯环，X为—O—，—N═，—NR3—或—CHR3—，R2为酰基，可选的酯化或硫酯化羧基，可选的取代的氨基甲酰基或可选的取代的氨基基团等，破折号表示单键或双键，而R1为氢原子，可选的取代的碳氢基团，可选的取代的杂环基团等。

  公开号：

  US20050148624A1
• 作为产物：
  描述：

  N-苯基双(三氟甲烷磺酰)亚胺 、 methyl 6-chloro-4-hydroxy-2-[4-(methylsulfonyl)benzyl]-1-oxo-1,2-dihydroisoquinoline-3-carboxylate 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以48%的产率得到methyl 6-chloro-2-[4-(methylsulfonyl)benzyl]-1-oxo-4-{[(trifluoromethyl)sulfonyl]oxy}-1,2-dihydroisoquinoline-3-carboxylate
  参考文献：
  名称：

  Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (1)

  摘要：

  A novel series of 4-phenylisoquinolones were synthesized and evaluated as c-Jun N-terminal kinase (JNK) inhibitors. Initial modi. cation at the 2- and 3-positions of the isoquinolone ring of hit compound 4, identified from high-throughput screening, led to the lead compound 6b. The optimization was carried out using a JNK1-binding model of 6b and several compounds exhibited potent JNK inhibition. Among them, 11g significantly inhibited cardiac hypertrophy in rat pressure-overload models without affecting blood pressure and the concept of JNK inhibitors as novel therapeutic agents for heart failure was confirmed. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.02.027

文献信息

• JNK INHIBITOR
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1484320A1

  公开（公告）日：2004-12-08

  A JNK inhibitor containing a compound having an isoquinolinone skeleton or a salt thereof, such as a compound represented by the formula wherein ring A and ring B are each an optionally substituted benzene ring, X is -O-, -N=, -NR3- or -CHR3-, R2 is an acyl group, an optionally esterified or thioesterified carboxyl group, an optionally substituted carbamoyl group or an optionally substituted amino group and the like, a broken line shows a single bond or a double bond, and R1 is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like, and the like.

  一种含有异喹啉酮骨架或其盐的JNK抑制剂，例如由以下公式表示的化合物： 其中环A和环B分别是可选择取代的苯环，X是-O-，-N=，-NR3-或-CHR3-，R2是酰基，可选择酯化或硫酯化的羧基，可选择取代的氨基甲酰基或可选择取代的氨基等，虚线表示单键或双键，R1是氢原子，可选择取代的碳氢基团，可选择取代的杂环基团等。
• Jnk inhibitor
  申请人：Itoh Fumio

  公开号：US20050148624A1

  公开（公告）日：2005-07-07

  A JNK inhibitor containing a compound having an isoquinolinone skeleton or a salt thereof, such as a compound represented by the formula wherein ring A and ring B are each an optionally substituted benzene ring, X is —O—, —N═, —NR 3 — or —CHR 3 —, R 2 is an acyl group, an optionally esterified or thioesterified carboxyl group, an optionally substituted carbamoyl group or an optionally substituted amino group and the like, a broken line shows a single bond or a double bond, and R 1 is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like, and the like.

  含有异喹啉酮骨架或其盐的JNK抑制剂，例如由以下式表示的化合物：其中环A和环B均为可选取代的苯环，X为—O—，—N═，—NR3—或—CHR3—，R2为酰基，可选的酯化或硫酯化羧基，可选的取代的氨基甲酰基或可选的取代的氨基基团等，破折号表示单键或双键，而R1为氢原子，可选的取代的碳氢基团，可选的取代的杂环基团等。
• JNK inhibitor
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US07402595B2

  公开（公告）日：2008-07-22

  A JNK inhibitor containing a compound having an isoquinolinone skeleton or a salt thereof, such as a compound represented by the formula wherein ring A and ring B are each an optionally substituted benzene ring, X is —O—, —N═, —NR3— or —CHR3—, R2 is an acyl group, an optionally esterified or thioesterified carboxyl group, an optionally substituted carbamoyl group or an optionally substituted amino group and the like, a broken line shows a single bond or a double bond, and R1 is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like, and the like.

  一种含有异喹啉酮骨架或其盐的JNK抑制剂，例如由下式表示的化合物：其中环A和环B均为可选取代的苯环，X为—O—、—N═、—NR3—或—CHR3—，R2为酰基、可选酯化或硫酯化的羧基、可选取代的氨基甲酰基或可选取代的氨基基团等，破折号表示单键或双键，R1为氢原子、可选取代的碳氢基团、可选取代的杂环基团等。
• US7402595B2
  申请人：——

  公开号：US7402595B2

  公开（公告）日：2008-07-22
• Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (1)
  作者：Yasutomi Asano、Shuji Kitamura、Taiichi Ohra、Kazuyoshi Aso、Hideki Igata、Tomoko Tamura、Tomohiro Kawamoto、Toshimasa Tanaka、Satoshi Sogabe、Shin-ichi Matsumoto、Masashi Yamaguchi、Hiroyuki Kimura、Fumio Itoh

  DOI：10.1016/j.bmc.2008.02.027

  日期：2008.4

  A novel series of 4-phenylisoquinolones were synthesized and evaluated as c-Jun N-terminal kinase (JNK) inhibitors. Initial modi. cation at the 2- and 3-positions of the isoquinolone ring of hit compound 4, identified from high-throughput screening, led to the lead compound 6b. The optimization was carried out using a JNK1-binding model of 6b and several compounds exhibited potent JNK inhibition. Among them, 11g significantly inhibited cardiac hypertrophy in rat pressure-overload models without affecting blood pressure and the concept of JNK inhibitors as novel therapeutic agents for heart failure was confirmed. (c) 2008 Elsevier Ltd. All rights reserved.