methyl 2-fluoro-5-((5-oxo-5,6-dihydropyrido[3,2-d]pyridazin-8-yl)methyl)benzoate | 1036403-16-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 2-fluoro-5-((5-oxo-5,6-dihydropyrido[3,2-d]pyridazin-8-yl)methyl)benzoate
• 英文别名: Methyl 2-Fluoro-5-[(5-oxo-5,6-dihydropyrido[2,3-d]pyridazin-8-yl)methyl]benzoate；methyl 2-fluoro-5-[(5-oxo-6H-pyrido[2,3-d]pyridazin-8-yl)methyl]benzoate
• CAS: 1036403-16-3
• 化学式: C₁₆H₁₂FN₃O₃
• 分子量: 313.288
• InChiKey: NIEXBIJYAVPZBT-UHFFFAOYSA-N

物化性质

• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-fluoro-5-((5-oxo-5,6-dihydropyrido[3,2-d]pyridazin-8-yl)methyl)benzoate 在 platinum on carbon 、 氢气 、 溶剂黄146 作用下， 20.0 ℃ 、206.85 kPa 条件下， 反应 32.0h， 以84%的产率得到methyl 2-fluoro-5-((5-oxo-1,2,3,4,5,6-hexahydropyridino[3,2-d]pyridazine-8-yl)methyl)benzoate
  参考文献：
  名称：

  Discovery and SAR of orally efficacious tetrahydropyridopyridazinone PARP inhibitors for the treatment of cancer

  摘要：

  PARP-1, the most abundant member of the PARP superfamily of nuclear enzymes, has emerged as a promising molecular target in the past decade particularly for the treatment of cancer. A number of PARP-1 inhibitors, including veliparab discovered at Abbott, have advanced into different stages of clinical trials. Herein we describe the development of a new tetrahydropyridopyridazinone series of PARP-1 inhibitors. Many compounds in this class, such as 20w, displayed excellent potency against the PARP-1 enzyme with a K-i value of < 1 nM and an EC50 value of 1 nM in a C41 whole cell assay. The presence of the NH in the tetrahydropyridyl ring of the tetrahydropyridopyridazinone scaffold improved the pharmacokinetic properties over similar carbon based analogs. Compounds 8c and 20u are orally available, and have demonstrated significant efficacy in a B16 murine xenograft model, potentiating the efficacy of temozolomide (TMZ). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.06.021
• 作为产物：
  描述：

  2-(2-(3-溴-4-氟苯基)乙酰基)烟酸甲酯 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 三乙胺 、 肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~100.0 ℃ 、413.7 kPa 条件下， 反应 10.0h， 生成 methyl 2-fluoro-5-((5-oxo-5,6-dihydropyrido[3,2-d]pyridazin-8-yl)methyl)benzoate
  参考文献：
  名称：

  Discovery and SAR of orally efficacious tetrahydropyridopyridazinone PARP inhibitors for the treatment of cancer

  摘要：

  PARP-1, the most abundant member of the PARP superfamily of nuclear enzymes, has emerged as a promising molecular target in the past decade particularly for the treatment of cancer. A number of PARP-1 inhibitors, including veliparab discovered at Abbott, have advanced into different stages of clinical trials. Herein we describe the development of a new tetrahydropyridopyridazinone series of PARP-1 inhibitors. Many compounds in this class, such as 20w, displayed excellent potency against the PARP-1 enzyme with a K-i value of < 1 nM and an EC50 value of 1 nM in a C41 whole cell assay. The presence of the NH in the tetrahydropyridyl ring of the tetrahydropyridopyridazinone scaffold improved the pharmacokinetic properties over similar carbon based analogs. Compounds 8c and 20u are orally available, and have demonstrated significant efficacy in a B16 murine xenograft model, potentiating the efficacy of temozolomide (TMZ). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.06.021

文献信息

• INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE
  申请人：Gandhi Virajkumar B.

  公开号：US20080161280A1

  公开（公告）日：2008-07-03

  Inhibitors of poly(ADP-ribose)polymerase, ways to make them and methods of treating patients using them are disclosed.

  聚(ADP核糖)聚合酶抑制剂、制备方法以及利用它们治疗患者的方法被披露。
• Inhibitors of poly(ADP-ribose)polymerase
  申请人：Gandhi Virajkumar B.

  公开号：US08466150B2

  公开（公告）日：2013-06-18

  Inhibitors of poly(ADP-ribose)polymerase, ways to make them and methods of treating patients using them are disclosed.

  本发明揭示了聚(ADP-核糖)聚合酶的抑制剂、制备它们的方法以及使用它们治疗患者的方法。
• Inhibitors of poly(adp-ribose)polymerase
  申请人：Abbvie Inc.

  公开号：EP2698062A1

  公开（公告）日：2014-02-19

  A compound selected from the group consisting of 1-(2-fluoro-5-((4-oxo-3,4,5,6,7,8-hexahydrophthalazin-1-yl)methyl)phenyl)pyrrolidine-2,5-dione and 4-(3-(1,4-diazepan-1-ylcarbonyl)-4-fluorobenzyl)-5,6,7,8-tetrahydrophthalazin-1(2H)-one, or a pharmaceutically acceptable salt thereof, for use in treating leukemia, colon cancer, glioblastomas, lymphomas, melanomas, carcinomas of the breast or cervical carcinomas in a mammal by administering thereto a therapeutically acceptable amount of said compound.

  一种选自由 1-(2-氟-5-((4-氧代-3,4,5,6,7,8-六氢酞嗪-1-基)甲基)苯基)吡咯烷-2,5-二酮和 4-(3-(1,4-二氮杂环庚烷-1-基羰基)-4-氟苄基)-5,6,7,8-四氢酞嗪-1(2H)-酮组成的组的化合物、或其药学上可接受的盐，通过给哺乳动物施用治疗上可接受量的所述化合物，用于治疗白血病、结肠癌、胶质母细胞瘤、淋巴瘤、黑色素瘤、乳腺癌或宫颈癌。
• ULK1和PARP1双靶点抑制剂
  申请人：南京亘泰医药技术有限公司

  公开号：CN117658985A

  公开（公告）日：2024-03-08

  本发明涉及式I结构的化合物或其药学上可接受的盐、溶剂化物、活性代谢物、多晶型物、酯、光学异构体或前药，包含式I结构的化合物的药物组合物及其作为ULK1及PARP1双靶点抑制剂在抗肿瘤药物的用途。#imgabs0#
• US8466150B2
  申请人：——

  公开号：US8466150B2

  公开（公告）日：2013-06-18