1-(2-aminoethyl)-3,7,8,9-tetrahydro-6H-pyrrolo[3,2-f]isoquinolin-6-one | 1018720-28-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1-(2-aminoethyl)-3,7,8,9-tetrahydro-6H-pyrrolo[3,2-f]isoquinolin-6-one
• 英文别名: 1-(2-aminoethyl)-8,9-dihydro-3H-pyrrolo[3,2-f]isoquinolin-6(7H)-one；1-(2-aminoethyl)-3,7,8,9-tetrahydropyrrolo[3,2-f]isoquinolin-6-one
• CAS: 1018720-28-9
• 化学式: C₁₃H₁₅N₃O
• 分子量: 229.282
• InChiKey: AFJVHLMQYGQCRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  70.9
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(2-aminoethyl)-3,7,8,9-tetrahydro-6H-pyrrolo[3,2-f]isoquinolin-6-one 、 N,N-二甲基甘氨酸 在 PL-Mukaiyama 、 PS-dimethylaminopyridine 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 N2,N2-dimethyl-N-[2-(6-oxo-6,7,8,9-tetrahydro-3H-pyrrolo[3,2-f]isoquinolin-1-yl)ethyl]glycinamide
  参考文献：
  名称：

  Identification of aminoethyl pyrrolo dihydroisoquinolinones as novel poly(ADP-ribose) polymerase-1 inhibitors

  摘要：

  PARP inhibitors have been demonstrated to retard intracellular DNA repair and therefore sensitize tumor cells to cytotoxic agents or ionizing radiation. We report the identification of a novel class of PARP1 inhibitors, containing a pyrrolo moiety fused to a dihydroisoquinolinone, derived from virtual screening of the proprietary collection. SAR exploration around the nitrogen of the aminoethyl appendage chain of 1 led to compounds that displayed low nanomolar activity in a PARP1 enzymatic assay. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.06.031
• 作为产物：
  描述：

  2-(3-氯丙基)-1,3-二噁戊环 、 6-hydrazino-3,4-dihydroisoquinolin-1(2H)-one 以 乙醇 、 水 为溶剂， 反应 24.0h， 生成 3-(2-aminoethyl)-1,6,7,8-tetrahydro-5H-pyrrolo[2,3-g]isoquinolin-5-one 、 1-(2-aminoethyl)-3,7,8,9-tetrahydro-6H-pyrrolo[3,2-f]isoquinolin-6-one
  参考文献：
  名称：

  Identification of aminoethyl pyrrolo dihydroisoquinolinones as novel poly(ADP-ribose) polymerase-1 inhibitors

  摘要：

  PARP inhibitors have been demonstrated to retard intracellular DNA repair and therefore sensitize tumor cells to cytotoxic agents or ionizing radiation. We report the identification of a novel class of PARP1 inhibitors, containing a pyrrolo moiety fused to a dihydroisoquinolinone, derived from virtual screening of the proprietary collection. SAR exploration around the nitrogen of the aminoethyl appendage chain of 1 led to compounds that displayed low nanomolar activity in a PARP1 enzymatic assay. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.06.031

文献信息

• WO2008/41037
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] FUSED INDOLES AND INDAZOLES AS INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (PARP)<br/>[FR] INDOLES ET INDAZOLES FUSIONNÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA POLY(ADP-RIBOSE)POLYMÉRASE (PARP)
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2008041037A1

  公开（公告）日：2008-04-10

  [EN] The present invention relates to compounds of formula I: and pharmaceutically acceptable salts or tautomers thereof which are inhibitors of poly(ADP- ribose)polymerase (PARP) and thus useful for the treatment of cancer, inflammatory diseases, reperfusion injuries, ischaemic conditions, stroke, renal failure, cardiovascular diseases, vascular diseases other than cardiovascular diseases, diabetes mellitus, neurodegenerative diseases, retroviral infections, retinal damage, skin senescence and UV-induced skin damage, and as chemo-or radiosensitizers for cancer treatment.
  [FR] La présente invention concerne des composés répondant à la formule I :, et leurs sels ou tautomères pharmaceutiquement acceptables, qui se révèlent être des inhibiteurs de la poly(ADP-ribose)polymérase (PARP) et peuvent par conséquent servir à traiter le cancer, les maladies inflammatoires, les lésions de reperfusion, les pathologies ischémiques, l'accident vasculaire cérébral, l'insuffisance rénale, les maladies cardiovasculaires, les maladies vasculaires autres que les maladies cardiovasculaires, le diabète sucré, les maladies neurodégénératives, les infections rétrovirales, les lésions rétiniennes, la sénescence cutanée et les lésions cutanées induites par les UV. Les composés se révèlent également utiles en tant que chimiosensibilisateurs ou radiosensibilisateurs pour le traitement du cancer.
• Identification of aminoethyl pyrrolo dihydroisoquinolinones as novel poly(ADP-ribose) polymerase-1 inhibitors
  作者：Danila Branca、Mauro Cerretani、Philip Jones、Uwe Koch、Federica Orvieto、Maria Cecilia Palumbi、Michael Rowley、Carlo Toniatti、Ester Muraglia

  DOI：10.1016/j.bmcl.2009.06.031

  日期：2009.8

  PARP inhibitors have been demonstrated to retard intracellular DNA repair and therefore sensitize tumor cells to cytotoxic agents or ionizing radiation. We report the identification of a novel class of PARP1 inhibitors, containing a pyrrolo moiety fused to a dihydroisoquinolinone, derived from virtual screening of the proprietary collection. SAR exploration around the nitrogen of the aminoethyl appendage chain of 1 led to compounds that displayed low nanomolar activity in a PARP1 enzymatic assay. (C) 2009 Elsevier Ltd. All rights reserved.