(+/-)-10,10a-Dihydroimidazo<1,5-b>isoquinoline-1,3(2H,5H)-dione | 62373-30-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (+/-)-10,10a-Dihydroimidazo<1,5-b>isoquinoline-1,3(2H,5H)-dione
• 英文别名: 1,3-dioxo-5H-10,10a-dihydroimidazo<1,5-b>isoquinoline；10,10a-dihydroimidazo[1,5-b]isoquinoline-1,3(2H,5H)-dione；10,10a-dihydro-5H-imidazo[1,5-b]isoquinoline-1,3-dione；10,10a-dihydro-5H-imidazo[1,5-b]isoquinoline-1,3-dione；10,10a-Dihydro-1H,5H-imidazo[1,5-b]isoquinolin-1,3(2H)-dione
• CAS: 62373-30-2
• 化学式: C₁₁H₁₀N₂O₂
• 分子量: 202.213
• InChiKey: DOBOZPLUXSSGSV-UHFFFAOYSA-N

物化性质

• 熔点：
  228-230 °C
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+/-)-10,10a-Dihydroimidazo<1,5-b>isoquinoline-1,3(2H,5H)-dione 在 溴 、 乙酸酐 作用下， 以 溶剂黄146 为溶剂， 以78%的产率得到10-Bromo-1,3-dioxo-2,3-dihydro-1H-imidazo<1,5-b>isoquinolinium bromide
  参考文献：
  名称：

  Niopas, Ioannis; Smail, Gordon A., Journal of the Chemical Society. Perkin transactions I, 1991, # 1, p. 113 - 117

  摘要：

  DOI：
• 作为产物：
  描述：

  (10aS)-10,10a-dihydroimidazo[1,5-b]isoquinoline-1,3(2H,5H)-dione 在 三乙胺 作用下， 以 乙醇 为溶剂， 生成 (+/-)-10,10a-Dihydroimidazo<1,5-b>isoquinoline-1,3(2H,5H)-dione
  参考文献：
  名称：

  Kinetics and mechanism of racemization of Tic-hydantoins, potent sigma-1 agonists

  摘要：

  The configurational stability of seven Tic-hydantoin sigma-1 agonists 1-7 was studied in organic and aqueous media to mimic conditions encountered during either their synthesis or their evaluation as a drug candidate (physico chemical property determination and pharmacological study). This study was performed from the enantiomers directly obtained by asymmetric synthesis (hydantoins 1,3-7) or after semi-preparative separation of the racemic obtained according to the same asymmetric procedure (thiohydantoin 2), by chiral HPLC. The racemization phenomenon was followed using recently validated chiral HPLC and capillary electrophoresis separation methods using derivatized cellulose and amylose chiral stationary phases (Chiralcel OD-H and Chiralpak AD) and highly sulphated cyclodextrins [highly S-beta-CD in the background electrolyte (BGE)], respectively. The kinetic parameters (rate constant, half-life and apparent free energy barriers) of racemization were calculated using a first-order reaction model. The influence of the acid-base content, pH in aqueous medium, concentration of the buffer, and temperature were investigated. The fastest racemization rates were observed under basic conditions. All hydantoins were shown to present the same magnitude of configurational stability, whereas thiohydantoin 2 was characterized by a high chiral instability, especially in ethanolic and aqueous media: its high instability in ethanol explains that a racemic mixture was obtained after asymmetric synthesis; its instantaneous racemization observed from the neutral pH makes the preparation of the enantiomers of 2 not relevant. Finally, the mechanism of racemization was elucidated using nuclear magnetic resonance (NMR): the comparison of the kinetics of the deuteration to the kinetics of the racemization suggests the involvement of a common reaction mechanism of S(E)1 type for hydantoin 1, while an S(E)2 type reaction seems to be involved for thiohydantoin 2. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2011.01.015

文献信息

• New Synthesis of Tic-Hydantoins Sigma-1 Ligands and Pharmacological Evaluation on Cocaine-Induced Stimulant Effects
  作者：M. Toussaint、M.-A. Debreu-Fontaine、T. Maurice、P. Melnyk

  DOI：10.2174/157340610793563956

  日期：2010.11.1

  Activation of the newly identified σ1 chaperone protein is involved in several aspects of the psychostimulant and addictive effects of cocaine. The development of ligands that selectively target the σ1 protein may lead to putative potent anti-cocaine agents. We report here a new and more convergent synthetic pathway to amino side chain substituted hydantoins. Twenty new analogs of our lead compound were synthesized. None of them showed better in vitro affinity for σ1 receptor than our lead compound. Nevertheless, three of them, obtained as racemates, showed high in vitro affinity and selectivity for σ1 receptor. A preliminary in vivo evaluation of their pharmacological activity identified compound 22 as one that increases cocaine-induced locomotor stimulation and therefore acts as a potential efficient σ1 agonist.

  新发现的伴侣蛋白σ1的激活涉及可卡因的精神刺激和成瘾效应的多个方面。开发选择性靶向σ1蛋白的配体可能会导致潜在强效抗可卡因药物的诞生。本文报道了一种新的、更趋同的合成途径，用于氨基酸侧链取代的乙内酰脲。合成了20种新的先导化合物类似物。其中没有一种在体外对σ1受体的亲和力超过先导化合物。然而，作为消旋体制备的三种化合物显示出对σ1受体的高体外亲和力和选择性。对它们药理活性的初步体内评价确定化合物22为一种能增强可卡因诱导的运动刺激作用的化合物，因此可作为潜在的高效σ1激动剂。
• IMIDAZOLIDINE CARBOXAMIDE DERIVATIVES AS LIPASE AND PHOSPHOLIPASE INHIBITORS
  申请人：ZOLLER Gerhard

  公开号：US20100105719A1

  公开（公告）日：2010-04-29

  The present invention relates to imidazolidinecarboxamide derivatives of the general formula I, wherein R, R1, R2, X and Y are as defined herein, or pharmaceutically usable salts thereof and the use thereof as medicinal substances.

  本发明涉及一般式I的咪唑啉羧酰胺衍生物，其中R、R1、R2、X和Y如本文所定义，或其药用盐以及其作为药用物质的用途。
• 2-[2-(Pipe
  申请人：Morton-Norwich Products, Inc.

  公开号：US04001245A1

  公开（公告）日：1977-01-04

  The title compound possesses pharmacological activity as an anti-inflammatory agent.

  这个标题化合物具有药理活性，作为一种抗炎剂。
• Pyridine compounds as inhibitors of dipeptidyl peptidase IV
  申请人：Oi Satoru

  公开号：US20070037807A1

  公开（公告）日：2007-02-15

  A compound represented by the formula wherein R 1 and R 2 are the same or different and each is an optionally substituted hydrocarbon group or an optionally substituted hydroxy group; R 3 is an optionally substituted aromatic group; R 4 is an optionally substituted amino group; L is a divalent chain hydrocarbon group; Q is a bond or a divalent chain hydrocarbon group; and X is a hydrogen atom, a cyano group, a nitro group, an acyl group, a substituted hydroxy group, an optionally substituted thiol group, an optionally substituted amino group or an optionally substituted cyclic group; provided that when X is an ethoxycarbonyl group, then Q is a divalent chain hydrocarbon group. The compound has a peptidase inhibitory action, is useful as an agent for the prophylaxis or treatment of diabetes and the like, and is superior in efficacy, duration of action, specificity, lower toxicity and the like.

  该化合物的化学式为其中R1和R2是相同或不同的可选择取代的烃基或可选择取代的羟基；R3是可选择取代的芳香基；R4是可选择取代的氨基；L是二价链烃基；Q是键或二价链烃基；X是氢原子、氰基、硝基、酰基、可选择取代的羟基、可选择取代的硫醇基、可选择取代的氨基或可选择取代的环状基；但当X是乙氧羰基时，Q是二价链烃基。该化合物具有肽酶抑制作用，可用作预防或治疗糖尿病等药物，具有优异的疗效、持续时间、特异性、低毒性等特点。
• Imidazolidine carboxamide derivatives as lipase and phospholipase inhibitors
  申请人：Zoller Gerhard

  公开号：US08735437B2

  公开（公告）日：2014-05-27

  The present invention relates to imidazolidinecarboxamide derivatives of the general formula I, wherein R, R1, R2, X and Y are as defined herein, or pharmaceutically usable salts thereof and the use thereof as medicinal substances.

  本发明涉及通式I的咪唑啉羧酰胺衍生物，其中R、R1、R2、X和Y如本文所定义，或其药学可用盐，并将其用作药物物质。