6,7-dichloro-4-(3-([4-(n,n-dimethylglycyl)piperazin-1-yl]carbonyl)-4-fluorobenzyl)pyrrolo[1,2-a]pyrazin-1(2H)-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 6,7-dichloro-4-(3-([4-(n,n-dimethylglycyl)piperazin-1-yl]carbonyl)-4-fluorobenzyl)pyrrolo[1,2-a]pyrazin-1(2H)-one
• 英文别名: 6,7-dichloro-4-(3-(4-(2-(dimethylamino)acetyl)piperazine-1-carbonyl)-4-fluorobenzyl)pyrrolo[1,2-a]pyrazin-1(2H)-one；6,7-dichloro-4-[[3-[4-[2-(dimethylamino)acetyl]piperazine-1-carbonyl]-4-fluorophenyl]methyl]-2H-pyrrolo[1,2-a]pyrazin-1-one
• 化学式: C₂₃H₂₄Cl₂FN₅O₃
• 分子量: 508.38
• InChiKey: URRPAFUDRLDWED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  77.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6,7-dichloro-4-[4-fluoro-3-(piperazin-1-ylcarbonyl)benzyl]pyrrolo[1,2-a]pyrazin-1(2H)-one 、 N,N-二甲基甘氨酸 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 6,7-dichloro-4-(3-([4-(n,n-dimethylglycyl)piperazin-1-yl]carbonyl)-4-fluorobenzyl)pyrrolo[1,2-a]pyrazin-1(2H)-one
  参考文献：
  名称：

  Identification and SAR of novel pyrrolo[1,2-a]pyrazin-1(2H)-one derivatives as inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1)

  摘要：

  Herein we describe the discovery of a novel series of pyrrolo[1,2-a]pyrazin-1(2H)-one PARP inhibitors. Optimization led to compounds that display excellent PARP-1 enzyme potency and inhibit the proliferation of BRCA deficient cells in the low double-digit nanomolar range showing excellent selectivity over BRCA proficient cancer cells. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.026

文献信息

• Pyrrolo[1,2-A] Pyrazin-1(2H)-One and Pyrrolo[1,2-D][1,2,4]Triazin-1(2H)-One Derivatives as Inhibitors of Poly(Adp-Ribose)Polymerase (Parp)
  申请人：Jones Philip

  公开号：US20090209523A1

  公开（公告）日：2009-08-20

  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.

  本发明涉及式I的化合物及其药学上可接受的盐或互变异构体，其作为poly(ADP-核糖)聚合酶（PARP）的抑制剂，因此在癌症治疗、炎症性疾病、再灌注损伤、缺血性疾病、中风、肾衰竭、心血管疾病、除心血管疾病外的血管疾病、糖尿病、神经退行性疾病、逆转录病毒感染、视网膜损伤、皮肤老化和紫外线诱导的皮肤损伤中有用，并可用作癌症治疗的化疗或放射敏化剂。
• PYRROLO[1,2-A]PYRAZIN-1(2H)-ONE AND PYRROLO[1,2-D][1,2,4]TRIAZIN-1(2H)-ONE DERIVATIVES AS INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE(PARP)
  申请人：Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A.

  公开号：EP2032140A1

  公开（公告）日：2009-03-11
• US7834015B2
  申请人：——

  公开号：US7834015B2

  公开（公告）日：2010-11-16
• [EN] PYRROLO[1,2-A]PYRAZIN-1(2H)-ONE AND PYRROLO[1,2-D][1,2,4]TRIAZIN-1(2H)-ONE DERIVATIVES AS INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE(PARP)<br/>[FR] DÉRIVÉS DE PYRROLO[1,2-A]PYRAZIN-1(2H)-ONE ET DE PYRROLO[1,2-D][1,2,4]TRIAZIN-1(2H)-ONE UTILISÉS EN TANT QU'INHIBITEURS DE LA POLY(ADP-RIBOSE)POLYMÉRASE (PARP)
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2007138355A1

  公开（公告）日：2007-12-06

  [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 des sels ou des tautomères pharmaceutiquement acceptables de ces composés, qui sont des inhibiteurs de la poly(ADP-ribose)polymérase (PARP) et se révèlent en conséquence utiles pour le traitement du cancer, de maladies inflammatoires, de lésions dues à une reperfusion, de pathologies ischémiques, d'un accident vasculaire cérébral, d'une insuffisance rénale, de maladies cardiovasculaires, de maladies vasculaires autres que les maladies cardiovasculaires, du diabète sucré, de maladies neurodégénératives, d'infections rétrovirales, d'un dommage rétinien, d'une sénescence de la peau et d'une lésion cutanée induite par les UV, de même qu'ils se révèlent utiles comme chimiosensibilisateurs ou radiosensibilisateurs pour le traitement du cancer.
• Identification and SAR of novel pyrrolo[1,2-a]pyrazin-1(2H)-one derivatives as inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1)
  作者：Giovanna Pescatore、Danila Branca、Fabrizio Fiore、Olaf Kinzel、Laura Llauger Bufi、Ester Muraglia、Federica Orvieto、Michael Rowley、Carlo Toniatti、Caterina Torrisi、Philip Jones

  DOI：10.1016/j.bmcl.2009.12.026

  日期：2010.2

  Herein we describe the discovery of a novel series of pyrrolo[1,2-a]pyrazin-1(2H)-one PARP inhibitors. Optimization led to compounds that display excellent PARP-1 enzyme potency and inhibit the proliferation of BRCA deficient cells in the low double-digit nanomolar range showing excellent selectivity over BRCA proficient cancer cells. (C) 2009 Elsevier Ltd. All rights reserved.