5,6-dimethoxy-1-oxo-indan-2-carbaldehyde | 91963-73-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 5,6-dimethoxy-1-oxo-indan-2-carbaldehyde
• 英文别名: 5,6-Dimethoxy-1-oxo-indan-2-carbaldehyd；2-Formyl-5,6-dimethoxy-1-hydrindon；5,6-Dimethoxy-3-oxo-1,2-dihydroindene-2-carbaldehyde
• CAS: 91963-73-4
• 化学式: C₁₂H₁₂O₄
• 分子量: 220.225
• InChiKey: OQWWQBFOXHRUSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5,6-dimethoxy-1-oxo-indan-2-carbaldehyde 在 溶剂黄146 、 肼 作用下， 以 乙醇 为溶剂， 生成 6,7-dimethoxy-1,4-dihydroindeno[1,2-c]pyrazole
  参考文献：
  名称：

  Discovery of 4′-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-benzonitriles and 4′-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-pyridine-2′-carbonitriles as potent checkpoint kinase 1 (Chk1) inhibitors

  摘要：

  An extensive structure-activity relationship study of the 3-position of a series of tricyclic pyrazole-based Chk1 inhibitors is described. As a result, 4'-,1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-benzonitriles (4) and 4'-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)pyridine-2'-carbonitriles (29) emerged as new lead series. Compared with the original lead compound 2, these new leads fully retain the biological activity in both enzymatic inhibition and cell-based assays. More importantly, the new leads 4 and 29 exhibit favorable physicochemical properties such as lower molecular weight, lower Clog P, and the absence of a hydroxyl group. Furthermore, structure-activity relationship studies were performed at the 6- and 7-positions of 4, which led to the identification of ideal Chk1 inhibitors 49, 50, 51, and 55. These compounds not only potently inhibit Chk1 in an enzymatic assay but also significantly potentiate the cytotoxicity of DNA-damaging agents in cell-based assays while they show little single agent activity. A cell cycle analysis by FACS confirmed that these Chk1 inhibitors efficiently abrogate the G2/M and S checkpoints induced by DNA-damaging agent. The current work paved the way to the identification of several potent Chk1 inhibitors with good pharmacokinetics that are suitable for in vivo study with oral dosing. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.102
• 作为产物：
  描述：

  5,6-二甲氧基茚酮 在 formic acid ester 、 sodium amide 作用下， 生成 5,6-dimethoxy-1-oxo-indan-2-carbaldehyde
  参考文献：
  名称：

  Engels; Perkin; Robinson, Journal of the Chemical Society, 1908, vol. 93, p. 1152

  摘要：

  DOI：

文献信息

• PSIORZ, MANFRED;HEIDER, JOACHIM;BOMHARD, ANDREAS;HAUEL, NORBERT;NOLL, KLA+
  作者：PSIORZ, MANFRED、HEIDER, JOACHIM、BOMHARD, ANDREAS、HAUEL, NORBERT、NOLL, KLA+

  DOI：——

  日期：——
• Neue Naphtalin- und Indanderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu deren Herstellung
  申请人：Dr. Karl Thomae GmbH

  公开号：EP0259782B1

  公开（公告）日：1990-12-27
• [EN] NOVEL PROCESS FOR PRODUCTION OF HIGHLY PURE POLYMORPH (I) DONEPEZIL HYDROCHLORIDE<br/>[FR] NOUVEAU PROCÉDÉ POUR LA PRODUCTION DE CHLORHYDRATE DE DONÉPÉZIL POLYMORPHE (I) EXTRÊMEMENT PUR
  申请人：RICHTER GEDEON VEGYESZET

  公开号：WO2007072087A2

  公开（公告）日：2007-06-28

  [EN] The present invention provides a novel, industrially realisable and economically preferable process for production of highly pure l-benzyl-4-[(5,6-dimethoxy-l-indanon)-2-yl]methyl piperidine hydrochloride, i.e., donepezil hydrochloride shown in the following reaction scheme, in Polymorph (I) morphological crystal form. (I) In one of the key steps of the process, during the hydrogenation 5,6-dimethoxy-2-(pyridine-4-yhnethylene)indan-l-one hydrochloride is saturated using Pd carbon to get 4-[(5,6-dimethoxy-l-indanon)-2-yl]-methyl piperidine at more than 97 % HPLC purity. In the crystallization step donepezil-hydrochloride is crystallized from an aqueous alcoholic solvent to get Polymorph (I) in at least 99.95 % HPLC purity.
  [FR] La présente invention concerne un nouveau procédé industriellement réalisable et économiquement préférable pour la production de chlorhydrate de 1-benzyl-4-[(5,6-diméthoxy-1-indanon)-2-yl]méthylpipéridine, c'est-à-dire de chlorhydrate de donépézil, extrêmement pur, représenté dans le schéma de réaction suivant, sous la forme de cristaux morphologiques polymorphes (I). (I) Dans une des étapes clés du procédé, au cours de l'hydrogénation, le chlorhydrate de 5,6-diméthoxy-2-(pyridin-4-ylméthylène)indan-1-one est saturé en utilisant du Pd sur carbone pour obtenir de la 4-[(5,6-diméthoxy-1-indanon)-2-yl]méthylpipéridine à plus de 97 % de pureté telle que déterminée par HPLC. Dans l'étape de cristallisation le chlorhydrate de donépézil est cristallisé dans un solvant alcoolique aqueux pour obtenir le polymorphe (I) ayant une pureté d'au moins 99,95 % telle que déterminée par HPLC.