3,3-dimethyl-isoindolin-1-one-imine | 854694-37-4

• 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: 3,3-dimethyl-isoindolin-1-one-imine
• 英文别名: 3,3-Dimethyl-isoindolin-1-on-imin；1,1-Dimethyl-1h-isoindol-3-amine；3,3-dimethylisoindol-1-amine
• CAS: 854694-37-4
• 化学式: C₁₀H₁₂N₂
• 分子量: 160.219
• InChiKey: RSWYTHKZAKEODI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  38.4
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3,3-dimethyl-isoindolin-1-one-imine 在 盐酸 、 水 作用下， 生成 2,3-二氢-3,3-二甲基-1H-异吲哚-1-酮
  参考文献：
  名称：

  Barrett et al., Journal of the Chemical Society, 1940, p. 1076,1078

  摘要：

  DOI：
• 作为产物：
  描述：

  甲基碘化镁 、 1,2-二氰基苯 在 乙醚 、 苯 作用下， 生成 3,3-dimethyl-isoindolin-1-one-imine
  参考文献：
  名称：

  Non-linear mixed effects modeling of sparse concentration data from rats: Application to a glycogen phosphorylase inhibitor

  摘要：

  We investigated the use of non-linear mixed effects modeling in two preclinical studies of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB). In a 28-day repeated-dose toxicity study rats were dosed once daily p.o. with 0, 20, 45, 100, or 470 mg/kg of DAB in aqueous solutions by oral gavage. Three blood samples were obtained from each animal using a staggered sampling scheme. During the cause of model development, data were included from a safety pharmacological cardiovascular study, in which rats were dosed once orally with 0, 4, 40, or 400 mg/kg of DAB thereby enabling an extension of the dose range of the model. DAB was assayed in plasma using a validated LC/MS/MS method. Non-linear mixed effects modeling was performed using the software NONMEM. The covariate analysis comprised dose, sex and time. Exposure results (C-max, AUC) obtained by mixed effects modeling were compared to results from noncompartmental analysis using naive pooling of data. The final model was a one-compartment model with first order absorption and a saturation-like dose dependent increase of the (oral) clearance (CL/f) and volume of distribution (V/f). Furthermore, V/f increased (by 55%) from Day 1 to Day 28. The dose dependencies of CL/f and V/f were most likely due to dose dependent decreases of the fraction systemically absorbed (f). The mechanism behind the dose dependencies may be saturation of a (putative) carrier mediated transport or modulation of tight junctions causing a reduced paracellular transport across the intestinal epithelium. Exposure results obtained from the model compared well with results obtained using noncompartmental analysis. An analysis of the data requirements for non-linear mixed effects modeling showed that at least three concentration values per animal were required for model development. We conclude that non-linear mixed effects modeling is feasible even with dose dependent pharmacokinetics in preclinical studies, such as 28-day toxicity studies in rodents. Supplementing data from additional preclinical studies may be required in order to extend the dose range. Non-linear mixed effects models may prove to be valuable tools in early PK and PK-PD modeling during drug development.

  DOI：

  10.1007/bf03190459

文献信息

• New Compounds 391
  申请人：Arnold James

  公开号：US20080171771A1

  公开（公告）日：2008-07-17

  This invention relates to novel compounds having the structural formula I below: and to their pharmaceutically acceptable salt, compositions and methods of use. These novel compounds provide a treatment or prophylaxis of cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.

  本发明涉及下面结构式I的新化合物，以及它们的药学上可接受的盐、组合物和使用方法。这些新化合物提供了治疗或预防认知障碍、阿尔茨海默病、神经退行性疾病和痴呆症的方法。
• New Compounds
  申请人：Arnold James

  公开号：US20110059992A1

  公开（公告）日：2011-03-10

  This invention relates to novel compounds having the structural formula I below: and to their pharmaceutically acceptable salt, compositions and methods of use. These novel compounds provide a treatment or prophylaxis of cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.

  本发明涉及结构式I的新化合物，以及它们的药学上可接受的盐、组合物和使用方法。这些新化合物提供了治疗或预防认知障碍、阿尔茨海默病、神经退行性和痴呆的方法。
• SUBSTITUTED ISOINDOLES AS BACE INHIBITORS AND THEIR USE
  申请人：AstraZeneca AB

  公开号：EP2035378A1

  公开（公告）日：2009-03-18
• US7855213B2
  申请人：——

  公开号：US7855213B2

  公开（公告）日：2010-12-21
• [EN] SUBSTITUTED ISOINDOLES AS BACE INHIBITORS AND THEIR USE<br/>[FR] ISOINDOLES SUBSTITUÉS EN TANT QU'INHIBITEURS DE BACE ET LEUR UTILISATION
  申请人：ASTRAZENECA AB

  公开号：WO2007149033A1

  公开（公告）日：2007-12-27

  [EN] This invention relates to novel compounds having the structural formula I and to their pharmaceutically acceptable salt, compositions and methods of use. These novel compounds provide a treatment or prophylaxis of cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.
  [FR] La présente invention concerne des nouveaux composés de formule structurale (I) et leur sel pharmaceutiquement acceptable, ainsi que leurs compositions et leurs procédés d'utilisation. Ces nouveaux composés permettent d'assurer le traitement ou la prophylaxie de troubles cognitifs, de la maladie d'Alzheimer, de la neurodégénérescence et de la démence.