(S)-4,5-dimethoxy-2-(1,2,3,4-tetrahydronaphthalen-1-yl)isoindoline-1,3-dione | 1123214-65-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: (S)-4,5-dimethoxy-2-(1,2,3,4-tetrahydronaphthalen-1-yl)isoindoline-1,3-dione
• 英文别名: (S)-4,5-dimethoxy-2-(1,2,3,4-tetrahydronaphthaIen-l-yl)isoindoIine-1,3-dione；4,5-dimethoxy-2-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]isoindole-1,3-dione
• CAS: 1123214-65-2
• 化学式: C₂₀H₁₉NO₄
• 分子量: 337.375
• InChiKey: LJZGBVBRWSZMMU-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-4,5-dimethoxy-2-(1,2,3,4-tetrahydronaphthalen-1-yl)isoindoline-1,3-dione 在 三溴化硼 、 水 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-4,5-dihydroxy-2-(1,2,3,4-tetrahydronaphthalen-1-yl)isoindoline-1,3-dione
  参考文献：
  名称：

  Diketoacid-genre HIV-1 integrase inhibitors containing enantiomeric arylamide functionality

  摘要：

  Using our recently disclosed 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one and 4,5-dihydroxy-1H-isoindole-1,3( 2H)-dione integrase inhibitors, we report differential effects on inhibitory potency induced by introduction of an alpha-chiral center into a key aryl substituent. We show that introduction of the chiral center is uniformly deleterious to binding, with the (R)-enantiomer being more deleterious than the (S)enantiomer. A greater enantiomeric difference in potency is shown by inhibitors that have restricted rotation of the aryl ring, with the larger difference being due to poorer potency of the (R)-enantiomer rather than higher potency of the (S)-enantiomer. The potency difference for enantiomers based on the isoindoline-1,3-dione ring system is less than for those derived from the isoindol-1-one ring system. Our findings provide useful information that should aid in understanding molecular binding interactions of DKA-derived IN inhibitors. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2009.05.008
• 作为产物：
  描述：

  4,5-二甲氧基-2-苯并呋喃-1,3-二酮 、 (S)-(+)-1,2,3,4-四氢-1-萘胺 在 三乙胺 作用下， 以 甲苯 为溶剂， 以8%的产率得到(S)-4,5-dimethoxy-2-(1,2,3,4-tetrahydronaphthalen-1-yl)isoindoline-1,3-dione
  参考文献：
  名称：

  Diketoacid-genre HIV-1 integrase inhibitors containing enantiomeric arylamide functionality

  摘要：

  Using our recently disclosed 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one and 4,5-dihydroxy-1H-isoindole-1,3( 2H)-dione integrase inhibitors, we report differential effects on inhibitory potency induced by introduction of an alpha-chiral center into a key aryl substituent. We show that introduction of the chiral center is uniformly deleterious to binding, with the (R)-enantiomer being more deleterious than the (S)enantiomer. A greater enantiomeric difference in potency is shown by inhibitors that have restricted rotation of the aryl ring, with the larger difference being due to poorer potency of the (R)-enantiomer rather than higher potency of the (S)-enantiomer. The potency difference for enantiomers based on the isoindoline-1,3-dione ring system is less than for those derived from the isoindol-1-one ring system. Our findings provide useful information that should aid in understanding molecular binding interactions of DKA-derived IN inhibitors. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2009.05.008

文献信息

• [EN] HYDRAZIDE, AMIDE, PHTHALIMIDE AND PHTHALHYDRAZIDE ANALOGS AS INHIBITORS OF RETROVIRAL INTEGRASE<br/>[FR] ANALOGUES D'HYDRAZIDE, D'AMIDE, DE PHTALIMIDE ET DE PHTALHYDRAZIDE EN TANT QU'INHIBITEURS DE L'INTÉGRASE RÉTROVIRALE
  申请人：US GOV HEALTH & HUMAN SERV

  公开号：WO2009026248A2

  公开（公告）日：2009-02-26

  The present invention provides catechol-containing hydrazides, amides, phthalimide and phthalhydrazide analogs. These compounds are inhibitors of retroviral integrase, an essential enzyme for the proliferation of retroviruses such as HIV-1. Also provided are pharmaceutical compositions comprising at least one of the catechol-containing hydrazides, amides, phthalimide or phthalhydrazide analogs and a method of using the hydrazide, amide, phthalimide and phthalhydrazide analogs to inhibit retroviral proliferation and as therapeutics for the treatment of AIDS.
• Diketoacid-genre HIV-1 integrase inhibitors containing enantiomeric arylamide functionality
  作者：Xue Zhi Zhao、Kasthuraiah Maddali、Christophe Marchand、Yves Pommier、Terrence R. Burke

  DOI：10.1016/j.bmc.2009.05.008

  日期：2009.7

  Using our recently disclosed 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one and 4,5-dihydroxy-1H-isoindole-1,3( 2H)-dione integrase inhibitors, we report differential effects on inhibitory potency induced by introduction of an alpha-chiral center into a key aryl substituent. We show that introduction of the chiral center is uniformly deleterious to binding, with the (R)-enantiomer being more deleterious than the (S)enantiomer. A greater enantiomeric difference in potency is shown by inhibitors that have restricted rotation of the aryl ring, with the larger difference being due to poorer potency of the (R)-enantiomer rather than higher potency of the (S)-enantiomer. The potency difference for enantiomers based on the isoindoline-1,3-dione ring system is less than for those derived from the isoindol-1-one ring system. Our findings provide useful information that should aid in understanding molecular binding interactions of DKA-derived IN inhibitors. Published by Elsevier Ltd.