(S)-2-(2,3-dihydro-1H-inden-1-yl)-4,5-dihydroxyisoindoline-1,3-dione | 1123214-95-8

• 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)-2-(2,3-dihydro-1H-inden-1-yl)-4,5-dihydroxyisoindoline-1,3-dione
• 英文别名: 2-[(1S)-2,3-dihydro-1H-inden-1-yl]-4,5-dihydroxyisoindole-1,3-dione
• CAS: 1123214-95-8
• 化学式: C₁₇H₁₃NO₄
• 分子量: 295.295
• InChiKey: ANEUNEGOGJPVGI-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  77.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (S)-2-(2,3-dihydro-1H-inden-1-yl)-4,5-dimethoxyisoindoline-1,3-dione 在 三溴化硼 、 水 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-2-(2,3-dihydro-1H-inden-1-yl)-4,5-dihydroxyisoindoline-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] SQUARATE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA SQUARATE KINASE
  申请人：WYETH CORP

  公开号：WO2009012375A2

  公开（公告）日：2009-01-22

  The present application provides compounds of Formula (I): and pharmaceutically acceptable salts thereof and pharmaceutical compositions thereof, wherein Het, R4, R9, and R10 are defined herein. Compounds of formula (I) are useful as inhibitors of MAP kinase activated protein kinase 2 (MK2).
• [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.