5,6-dihydroxyisoindoline hydrobromide | 105358-67-6

• 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: 5,6-dihydroxyisoindoline hydrobromide
• 英文别名: Isoindoline-5,6-diol hydrobromide；2,3-dihydro-1H-isoindole-5,6-diol;hydrobromide
• CAS: 105358-67-6
• 化学式: BrH*C₈H₉NO₂
• 分子量: 232.077
• InChiKey: UOTXRJSAADCQEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.28
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  52.5
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,6-dihydroxyisoindoline hydrobromide 在 potassium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 、 乙腈 为溶剂， 反应 20.0h， 生成 N-<(tert-butyloxy)carbonyl>-5-hydroxy-6-methoxyisoindoline
  参考文献：
  名称：

  The Discovery of Capsazepine, the First Competitive Antagonist of the Sensory Neuron Excitants Capsaicin and Resiniferatoxin

  摘要：

  Capsaicin and resiniferatoxin are natural products which act specifically on a subset of primary afferent sensory neurons to open a novel cation-selective ion channel in the plasma membrane. These sensory neurons are involved in nociception, and so, these agents are targets for the design of a novel class of analgesics. Although synthetic agonists at the capsaicin receptor have been described previously, competitive antagonists at this receptor would be interesting and novel pharmacological agents. Structure-activity relationships for capsaicin agonists have previously been rationalized, by ourselves and others, by dividing the capsaicin molecule into three regions-the A (aromatic ring)-, B (amide bond)-, and C (hydrophobic side chain)-regions. In this study, the effects on biological activity of conformational constraint of the A-region with respect to the B-region are discussed. Conformational constraint was achieved by the introduction of saturated ring systems of different sizes. The resulting compounds provided agonists of comparable potency to unconstrained analogues as well as a moderately potent antagonist, capsazepine. This compound is the first competitive antagonist of capsaicin and resiniferatoxin to be described and is active in various systems, in vitro and in vivo. It has recently attracted considerable interest as a tool for dissecting the mechanisms by which capsaicin analogues evoke their effects. NMR spectroscopy and X-ray crystallography experiments, as well as molecular modeling techniques, were used to study the conformational behavior of a representative constrained agonist and antagonist. The conformation of the saturated ring contraint in the two cases was found to differ markedly, dramatically affecting the relative disposition of the A-ring and B-region pharmacophores. In agonist structures, the A- and B-regions were virtually coplanar in contrast to those in the antagonist, in which they were approximately orthogonal. A rationale for agonist and antagonist activity at the capsaicin receptor is proposed, based on the consideration of these conformational differences.

  DOI：

  10.1021/jm00039a006
• 作为产物：
  描述：

  5,6-dimethoxy-2-[(4-methylphenyl)sulfonyl]isoindoline 在 氢溴酸 、 丙酸 、 苯酚 作用下， 反应 4.0h， 以67%的产率得到5,6-dihydroxyisoindoline hydrobromide
  参考文献：
  名称：

  SAR studies of capsazepinoid bronchodilators. Part 1: The importance of the catechol moiety and aspects of the B-ring structure

  摘要：

  Capsazepine as well as its derivatives and analogues are general inhibitors of constriction of human small airways. From a systematic variation of the capsazepine structure, divided into four regions, SARs were established. This part concerns the catechol moiety of the A-ring as well as the 2,3,4,5-tetrahydro-1H-2-azepine moiety (the B-ring) of capsazepine. It is revealed that a conformational constrain (as a fused ring) is important and that compounds with a six-membered B-ring (as a 1,2,3,4-tetrahydroisoquinoline) in general are more potent than the corresponding isoindoline, 2,3,4,5 -tetrahydro-1H-2-benzazepi ne and 2,3,4,5-tetrahydro-1H-3-benzazepine derivatives. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.055

文献信息

• SAR studies of capsazepinoid bronchodilators. Part 2: Chlorination and catechol replacement in the A-ring
  作者：Magnus Berglund、María F. Dalence-Guzmán、Staffan Skogvall、Olov Sterner

  DOI：10.1016/j.bmc.2007.11.061

  日期：2008.3

  airways. From a systematic variation of the capsazepine structure, divided into four regions, SARs were established. This paper concerns the chlorination of the A-ring as well as the replacement of the catechol with bioisosteric groups. It is revealed that chlorination of the A-ring has a profound effect on activity. Moreover, di-chlorination of the 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline structure

  辣椒素及其衍生物和类似物是人类小气道收缩的一般抑制剂。从辣椒素结构的系统变化分为四个区域，建立了SAR。本文涉及A环的氯化以及生物等位基团取代邻苯二酚。揭示了A环的氯化对活性有深远的影响。此外，与卡塞平相比，对6,7-二羟基-1,2,3,4-四氢异喹啉结构进行二氯化处理会导致效力增加10倍。
• Isoindoline derivatives and processes for their preparation
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US04987235A1

  公开（公告）日：1991-01-22

  A compound having the formula: ##STR1## wherein R is a hydrogen atom, a lower alkyl group, an alkanoyl group, an aralkyl group, an alkylsulfonyl group or an arylsulfonyl group, and R.sup.1 is a hydrogen atom or a protecting group for a hydroxyl group, or a salt thereof.

  一种具有以下化学式的化合物：##STR1## 其中R是氢原子、低碳烷基基团、烷酰基、芳基烷基基团、烷基磺酰基或芳基磺酰基，R.sup.1是氢原子或羟基的保护基，或其盐。
• [EN] BRONCHORELAXING COMPOUNDS<br/>[FR] COMPOSES BRONCHO-RELACHANTS
  申请人：RESPIRATORIUS AB

  公开号：WO2005070887A1

  公开（公告）日：2005-08-04

  A compound of the general formula (I) including its pharmaceutically acceptable acid addition salts formula (I) wherein A is CHR9, wherein R9 is H, C1-C6 alkyl;n is 1-3; B is CHR10, wherein R10 is H, C1-C6 alkyl; m is 1 or 2; D is O or S; E is CR11R12 or NR13, wherein R11 and R12 are, independent of each other, H or C1-C6 alkyl, R13 is H or C1-C6 alkyl; F is C1-C18 alkyl or R4-R7 cycloalkyl, which may be mono- or di-unsaturated and/or substituted, is useful in treating and preventing pulmonary disease characterized by bronchoconstriction; also disclosed is a pharmaceutical composition comprising the compound of formula (I), a pharmaceutical carrier and, optionally, an anti-asthmatic, a method for its manufacture, and a method for treating or preventing such disease.

  通式（I）的化合物及其药学上可接受的酸加合盐，其中A为CHR9，其中R9为H，C1-C6烷基；n为1-3；B为CHR10，其中R10为H，C1-C6烷基；m为1或2；D为O或S；E为CR11R12或NR13，其中R11和R12独立地为H或C1-C6烷基，R13为H或C1-C6烷基；F为C1-C18烷基或R4-R7环烷基，可以是单烯或双烯和/或取代的，用于治疗和预防以支气管收缩为特征的肺部疾病；还公开了包含通式（I）的药物组合物、药物载体和可选的抗哮喘药、其制造方法以及治疗或预防该疾病的方法。
• Cephalosporin derivatives
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US04677100A1

  公开（公告）日：1987-06-30

  A compound having the formula: ##STR1## wherein R.sup.1 is a straight chain, branched chain or cyclic lower alkyl group which may be substituted by a carboxyl group, and each of R.sup.2 and R.sup.3 which may be the same or different, is a hydrogen atom, a hydroxyl group, a methoxy group or an acetoxy group, and R.sup.4 is a hydroxyl group, a methoxy group or an acetoxy group; or a pharmaceutically acceptable salt, physiologically hydrolyzable ester or solvate thereof.

  一种化合物的化学式为：##STR1## 其中R.sup.1是一种直链、支链或环状低烷基，可以被羧基取代；R.sup.2和R.sup.3各自可以相同或不同，是氢原子、羟基、甲氧基或乙酰氧基；R.sup.4是羟基、甲氧基或乙酰氧基；或其药学上可接受的盐、生理水解酯或溶剂化物。
• Bronchorelaxing compounds
  申请人：Skogvall Staffan

  公开号：US20060040919A1

  公开（公告）日：2006-02-23

  A compound of the general formula (I) including its pharmaceutically acceptable acid addition salts wherein A is CHR 9 , wherein R 9 is H, C 1 -C 6 alkyl; n is 1-3; B is CHR 10 , wherein R 10 is H, C 1 -C 6 alkyl; m is 1 or 2; D is O or S; E is CR 11 R 12 or NR 13 , wherein R 11 and R 12 are, independent of each other, H or C 1 -C 6 alkyl, R 13 is H or C 1 -C 6 alkyl; F is C 1 -C 18 alkyl or R 4 -R 7 cycloalkyl, which may be mono- or di-unsaturated and/or substituted, is useful in treating and preventing pulmonary disease characterized by bronchoconstriction; also disclosed is a pharmaceutical composition comprising the compound of formula (I), a pharmaceutical carrier and, optionally, an anti-asthmatic, a method for its manufacture, and a method for treating or preventing such disease.

  化合物的一般式(I)及其药学上可接受的酸盐包括其中，其中A为CHR9，其中R9为H，C1-C6烷基；n为1-3；B为CHR10，其中R10为H，C1-C6烷基；m为1或2；D为O或S；E为CR11R12或NR13，其中R11和R12独立地为H或C1-C6烷基，R13为H或C1-C6烷基；F为C1-C18烷基或R4-R7环烷基，可以是单烯或双烯和/或取代的，用于治疗和预防以支气管收缩为特征的肺部疾病；还公开了包括式(I)化合物的药物组合物、药物载体和可选的抗哮喘药、其制造方法以及治疗或预防该疾病的方法。