rucaparib | 283173-02-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: rucaparib
• 英文别名: 2-[4-(Methylaminomethyl)phenyl]-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-9-one
• CAS: 283173-02-4
• 化学式: C₁₉H₁₉N₃O
• 分子量: 305.379
• InChiKey: SRQIXYAZHSQGIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  56.9
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-吲哚丙酸 在 aluminum (III) chloride 、 四(三苯基膦)钯 、 正丁基锂 、 氯化亚砜 、 盐酸羟胺 、 水 、 sodium acetate 、 sodium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 氯乙酰氯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 为溶剂， 反应 52.5h， 生成 rucaparib
  参考文献：
  名称：

  Poly(ADP-ribose) Polymerase in Neurodegeneration: Radiosynthesis and Radioligand Binding in ARC-SWE tg Mice

  摘要：

  We report the synthesis, radiosynthesis, and characterization of a radioligand for poly(ADP-ribose) polymerase (PARP). PARP is of central importance in cell homeostasis, neuroplasticity, and neurodegeneration in the brain. A radiolabeled PARP inhibitor was developed and used for autoradiographic quantification of PARP protein concentration in wild-type and transgenic rodent brains ex vivo in high resolution. The binding of [H-3]rucaparib was found to be confined to PARP-expressing domains, for example, cerebellar cortex or hippocampal regions in both models. Saturation binding experiments confirmed selective and reversible binding to a single site (K-d = 1.1 +/- 0.2 nM).

  DOI：

  10.1021/acschemneuro.8b00053

文献信息

• Tricyclic inhibitors of poly(ADP-ribose) polymerases
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：US06495541B1

  公开（公告）日：2002-12-17

  Compounds of the formula below are poly(ADP-ribosyl)transferase (PARP) inhibitors, and are useful as therapuetics in treatment of cancers and the amelioration of the effects of stroke, head trauma, and nuerodegenerative disease. As cancer therapuetics, the compounds of the invention may be used, e.g., in combination with cytotoxic agents and/or radiation.

  以下公式化合物是聚(ADP核糖基)转移酶（PARP）抑制剂，可用于治疗癌症并改善中风、头部创伤和神经退行性疾病的影响。作为癌症治疗药物，本发明的化合物可与细胞毒性药物和/或放射线结合使用。
• CRYSTALLINE OF CAMPHORSULFONIC ACID SALT OF RUCAPARIB AND METHOD OF PREPARING OF TRICYCLIC COMPOUNDS, RUCAPARIB AND CRYSTALLINE OF CAMPHORSULFONIC ACID SALT OF RUCAPARIB
  申请人：Formosa Laboratories, Inc.

  公开号：US20200165261A1

  公开（公告）日：2020-05-28

  A method of preparing a tricyclic compound of formula (I), comprising the step of converting a compound of formula (II) into a compound of formula (III); and hydrogenating the compound of formula (III) in the presence of hydrogenation catalyst and hydrogen to form the tricyclic compound of formula (I); wherein R 1 is H or a C 1-3 alkyl group; and R 2 is H, a halogen element or a C 1-3 alkyl group.

  一种制备化合物(I)的三环化合物的方法，包括将化合物(II)转化为化合物(III)的步骤；并在氢化催化剂和氢气的存在下氢化化合物(III)以形成化合物(I)的三环化合物；其中R1是H或C1-3烷基基团；R2是H、卤素元素或C1-3烷基基团。
• [EN] SALTS AND POLYMORPHS OF 8-FLUORO-2-{4-[(METHYLAMINO}METHYL]PHENYL}-1,3,4,5-TETRAHYDRO-6H-AZEPINO[5,4,3-CD]INDOL-6-ONE<br/>[FR] SELS ET POLYMORPHES DE LA 8-FLUORO-2-{4-[(MÉTHYLAMINO}MÉTHYL]PHÉNYL}-1,3,4,5-TÉTRAHYDRO-6H-AZÉPINO[5,4,3-CD]INDOL-6-ONE
  申请人：PFIZER

  公开号：WO2011098971A1

  公开（公告）日：2011-08-18

  The present invention relates to novel polymorphic forms of 8-fluoro-2-4- [(methylamino)methyl]phenyf}-1,3,4,5-tetrahydro-6H-azepino(5,4,3-cd]indol-6-one;(I), and to processes for their preparation. Such polymorphic forms may be a component of a pharmaceutical composition and may be used to treat a mammalian disease condition mediated by poly(ADP-ribose) polymerase activity including the disease condition such as cancer.

  本发明涉及8-氟-2-4-[(甲氨基)甲基]苯基}-1,3,4,5-四氢-6H-氮杂并[5,4,3-cd]吲哚-6-酮(I)的新型多形态，以及其制备方法。这些多形态可以成为制药组合物的组成部分，并可用于治疗由聚(ADP-核糖)聚合酶活性介导的哺乳动物疾病状态，包括癌症等疾病状态。
• [EN] TRICYCLIC INHIBITORS OF POLY(ADP-RIBOSE) POLYMERASES<br/>[FR] INHIBITEURS TRICYCLIQUES DE POLY(ADP-RIBOSE) POLYMERASES
  申请人：AGOURON PHARMA

  公开号：WO2000042040A1

  公开（公告）日：2000-07-20

  Compounds of formula (I) are poly(ADP-ribosyl)transferase (PARP) inhibitors, and are useful as therapeutics in treatment of cancers and the amelioration of the effects of stroke, head trauma, and neurodegenerative disease. As cancer therapeutics, the compounds of the invention may be used, e.g., in combination with cytotoxic agents and/or radiation.

  公式（I）的化合物是聚(ADP-核糖基)转移酶（PARP）抑制剂，并可用于治疗癌症和改善中风、头部创伤和神经退行性疾病的影响，作为治疗剂。作为癌症治疗剂，本发明的化合物可以与细胞毒性剂和/或放射线结合使用。
• LIPOIC ACID AND NITROXIDE DERIVATIVES AND USES THEREOF
  申请人：Salzman Andrew Lurie

  公开号：US20130116284A1

  公开（公告）日：2013-05-09

  Provided are bifunctional compounds comprising a poly(ADP-ribose) polymerase (PARP) inhibitor moiety and a reactive oxygen species (ROS) scavenger moiety, more particularly, a lipoic acid or cyclic nitroxide derivative, covalently attached either directly or via a linker, as well as pharmaceutical compositions comprising them. The compounds and pharmaceutical compositions are useful for prevention, treatment, or management of diseases, disorders and conditions associated with elevated PARP activity or expression.

  提供的是双功能化合物，包括聚(ADP-核糖)聚合酶（PARP）抑制剂基团和反应性氧自由基（ROS）清除剂基团，更具体地说，是硫辛酸或环状亚硝基衍生物，直接或通过连接剂共价连接，以及包含它们的制药组合物。这些化合物和制药组合物对于预防、治疗或管理与提高的PARP活性或表达相关的疾病、疾病和病况是有用的。