5-氟-8-(4-氟苯基)-2,7,8,9-四氢-9-(1-甲基-1H-1,2,4-噻唑-5-基)-3H-吡啶并[4,3,2-de]二氮杂萘-3-酮 | 1207454-56-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 5-氟-8-(4-氟苯基)-2,7,8,9-四氢-9-(1-甲基-1H-1,2,4-噻唑-5-基)-3H-吡啶并[4,3,2-de]二氮杂萘-3-酮
• 英文名称: talazoparib
• 英文别名: 5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one；(±)-5-fluoro-8-(4-fluorophenyl)-2,7,8,9-tetrahydro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-3H-pyrido[4,3,2-de]phthalazin-3-one；(±)-talazoparib；5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one；7-fluoro-11-(4-fluorophenyl)-12-(2-methyl-1,2,4-triazol-3-yl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one
• CAS: 1207454-56-5
• 化学式: C₁₉H₁₄F₂N₆O
• 分子量: 380.357
• InChiKey: HWGQMRYQVZSGDQ-UHFFFAOYSA-N

物化性质

• 密度：
  1.63±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  84.2
• 氢给体数：
  2
• 氢受体数：
  7

安全信息

• 储存条件：
  2-8℃

反应信息

• 作为反应物：
  描述：

  5-氟-8-(4-氟苯基)-2,7,8,9-四氢-9-(1-甲基-1H-1,2,4-噻唑-5-基)-3H-吡啶并[4,3,2-de]二氮杂萘-3-酮 在 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 二乙胺 为溶剂， 生成 (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one hydrochloride
  参考文献：
  名称：

  [EN] DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY (ADP-RIBOSE) POLYMERASE (PARP) FOR THE TREATMENT OF MULTIPLE MYELOMA
  [FR] INHIBITEURS DIHYDROPYRIDOPHTHALAZINONE DE POLY (ADP-RIBOSE) POLYMÉRASE (PARP) POUR LE TRAITEMENT DU MYÉLOME MULTIPLE

  摘要：

  提供了一种使用聚(ADP-核糖)聚合酶抑制剂治疗多发性骨髓瘤的方法，该抑制剂的化学式为(I)。

  公开号：

  WO2013028495A1
• 作为产物：
  描述：

  7-氟-2-(4-氟苯基)-3-(1-甲基-1H-1,2,4-三唑-5-基)-4-氧代-1,2,3 在 一水合肼 作用下， 以 甲醇 为溶剂， 以78.1%的产率得到5-氟-8-(4-氟苯基)-2,7,8,9-四氢-9-(1-甲基-1H-1,2,4-噻唑-5-基)-3H-吡啶并[4,3,2-de]二氮杂萘-3-酮
  参考文献：
  名称：

  [EN] DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY (ADP-RIBOSE) POLYMERASE (PARP) FOR THE TREATMENT OF MULTIPLE MYELOMA
  [FR] INHIBITEURS DIHYDROPYRIDOPHTHALAZINONE DE POLY (ADP-RIBOSE) POLYMÉRASE (PARP) POUR LE TRAITEMENT DU MYÉLOME MULTIPLE

  摘要：

  提供了一种使用聚(ADP-核糖)聚合酶抑制剂治疗多发性骨髓瘤的方法，该抑制剂的化学式为(I)。

  公开号：

  WO2013028495A1

文献信息

• [EN] METHODS OF USING DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY (ADP-RIBOSE)POLYMERASE (PARP)<br/>[FR] MÉTHODES D'UTILISATION D'INHIBITEURS DIHYDROPYRIDOPHTHALAZINONIQUES DE LA POLY(ADP-RIBOSE) POLYMÉRASE (PARP)
  申请人：BIOMARIN PHARM INC

  公开号：WO2011130661A1

  公开（公告）日：2011-10-20

  Provided herein are methods of treating cancer comprising administering a topoisomerase inhibitor, temozolomide, or a platin in combination with a Compound of Formula (I) or Formula (II), where the substituents Y, Z, A, B, R1, R2, R3, R4 and R5 are as defined herein.

  本文提供了治疗癌症的方法，包括联合给药拓扑异构酶抑制剂、替莫唑胺或铂类药物与式（I）或式（II）化合物的方法，其中取代基Y、Z、A、B、R1、R2、R3、R4和R5如本文所定义。
• DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (PARP)
  申请人：Wang Bing

  公开号：US20100035883A1

  公开（公告）日：2010-02-11

  A compound having the structure set forth in Formula (I) and Formula (II): wherein the substituents Y, Z, A, B, R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein. Provided herein are inhibitors of poly(ADP-ribose)polymerase activity. Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of a compound or pharmaceutical composition described herein to treat diseases, disorders and conditions that are ameliorated by the inhibition of PARP activity.

  具有以下结构的化合物：其中取代基Y、Z、A、B、R1、R2、R3、R4和R5如本处所定义。本文提供了聚(ADP核糖)聚合酶活性的抑制剂。本文还描述了包括至少一种本文描述的化合物的药物组合物，以及使用本文描述的化合物或药物组合物治疗通过抑制PARP活性而改善的疾病、疾病和症状。
• DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (PARP) FOR USE IN TREATMENT OF DISEASES ASSOCIATED WITH A PTEN DEFICIENCY
  申请人：Chu Daniel

  公开号：US20110190288A1

  公开（公告）日：2011-08-04

  A compound having the structure set forth in Formula (I) and Formula (II): wherein the substituents Y, Z, A, B, R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein. Provided herein are inhibitors of poly(ADP-ribose)polymerase activity. Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of a compound or pharmaceutical composition described herein to treat diseases, disorders and conditions associated with a PTEN deficiency that are ameliorated by the inhibition of PARP activity.

  化合物具有以下公式（I）和公式（II）所示的结构： 其中，取代基Y、Z、A、B、R1、R2、R3、R4和R5的定义如本文所述。本文提供了聚(ADP-核糖)聚合酶活性抑制剂。本文还描述了包括至少一种本文所述化合物的制药组合物，以及使用本文所述的化合物或制药组合物治疗与PTEN缺陷相关的疾病、紊乱和病况，这些疾病、紊乱和病况通过抑制PARP活性得到改善。
• [EN] CRYSTALLINE (8S,9R)-5-FLUORO-8-(4-FLUOROPHENYL)-9-(1-METHYL-1H-1,2,4-TRIAZOL-5-YL)-8,9-DIHYDRO-2H-PYRIDO[4,3,2-DE]PHTHALAZIN-3(7H)-ONE TOSYLATE SALT<br/>[FR] SEL TOSYLATE DE LA (8S,9R)-5-FLUORO-8-(4-FLUOROPHÉNYL)-9-(1-MÉTHYL-1H- 1,2,4-TRIAZOL-5-YL)-8,9-DIHYDRO-2H-PYRIDO[4,3,2-DE]PHTALAZIN-3(7H)-ONE CRISTALLIN
  申请人：BIOMARIN PHARM INC

  公开号：WO2012054698A1

  公开（公告）日：2012-04-26

  Provided herein are (8S, 9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-lH-1,2,4-triazol-5- yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt forms, including crystalline forms, and methods of their preparation. Pharmaceutical compositions comprising a (8S,9R)-5-fiuoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H- pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt are also provided, as are methods of using (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H- pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt to treat a disease or condition, such as a cancer.

  本文提供了(8S,9R)-5-氟-8-(4-氟苯基)-9-(1-甲基-1H-1,2,4-三唑-5-基)-8,9-二氢-2H-吡啶[4,3,2-de]萘并[3H]咔唑-3(7H)-酮甜酸盐形式，包括结晶形式，以及其制备方法。本文还提供了包含(8S,9R)-5-氟-8-(4-氟苯基)-9-(1-甲基-1H-1,2,4-三唑-5-基)-8,9-二氢-2H-吡啶[4,3,2-de]萘并[3H]咔唑-3(7H)-酮甜酸盐的药物组合物，以及使用(8S,9R)-5-氟-8-(4-氟苯基)-9-(1-甲基-1H-1,2,4-三唑-5-基)-8,9-二氢-2H-吡啶[4,3,2-de]萘并[3H]咔唑-3(7H)-酮甜酸盐治疗疾病或病症的方法，例如癌症。
• PROCESSES OF SYNTHESIZING DIHYDROPYRIDOPHTHALAZINONE DERIVATIVES
  申请人：Wang Bing

  公开号：US20110196153A1

  公开（公告）日：2011-08-11

  Provided herein are processes for synthesizing dihydropyridophthalazinone derivatives, such as for example, 5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one and its stereoisomers, which are potent poly(ADP-ribose)polymerase (PARP) inhibitors as well as novel synthetic intermediate compounds.

  本文提供了一种合成二氢吡啶并苯并噻唑酮衍生物的方法，例如5-氟-8-(4-氟苯基)-9-(1-甲基-1H-1,2,4-三唑-5-基)-8,9-二氢-2H-吡啶[4,3,2-de]苯并噻唑-3(7H)-酮及其立体异构体。这些化合物是有效的聚腺苷酸核苷酸聚合酶（PARP）抑制剂，同时也是新型的合成中间体化合物。