tert-butyl 4-[(trifluoromethane)sulfonyloxy]-1H,2H,3H-pyrrolo[2,3-c]pyridine-1-carboxylate | 1354454-94-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: tert-butyl 4-[(trifluoromethane)sulfonyloxy]-1H,2H,3H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 英文别名: Tert-butyl 4-(trifluoromethylsulfonyloxy)-2,3-dihydropyrrolo[2,3-c]pyridine-1-carboxylate；tert-butyl 4-(trifluoromethylsulfonyloxy)-2,3-dihydropyrrolo[2,3-c]pyridine-1-carboxylate
• CAS: 1354454-94-6
• 化学式: C₁₃H₁₅F₃N₂O₅S
• 分子量: 368.334
• InChiKey: HNFMAYHZPRXNHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  94.2
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[(trifluoromethane)sulfonyloxy]-1H,2H,3H-pyrrolo[2,3-c]pyridine-1-carboxylate 在 4-二甲氨基吡啶 、 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 作用下， 以 N,N-二甲基乙酰胺 、 二甲胺 为溶剂， 反应 1.08h， 生成 2,3-Dihydro-1H-pyrrolo[2,3-c]pyridine-4-carbonitrile
  参考文献：
  名称：

  1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile Derivatives as Potent and Tissue Selective Androgen Receptor Modulators

  摘要：

  We present a novel series of selective androgen receptor modulators (SARMs) which shows excellent biological activity and physical properties. 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)-indoline-4-carbonitriles showed potent binding to the androgen receptor (AR) and activated AR-mediated transcription in vitro. Representative compounds demonstrated diminished activity in promoting the intramolecular interaction between the AR carboxyl (C) and amino (N) termini. This N/C-termini interaction is a biomarker assay for the undesired androgenic responses in vivo. In orchidectomized rats, daily administration of a lead compound from this series showed anabolic activity by increasing levator ani muscle weight. Importantly, minimal androgenic effects (increased tissue weights) were observed in the prostate and seminal vesicles, along with minimal repression of circulating luteinizing hormone (LH) levels and no change in the lipid and triglyceride levels. This lead compound completed a two week rat toxicology study, and was well tolerated at doses up to 100 mg/kg/day, the highest dose tested, for 14 consecutive days.

  DOI：

  10.1021/jm401625b
• 作为产物：
  描述：

  4-羟基-3-硝基吡啶 在 哌啶 、 盐酸 、 bronze powder 、 palladium 10% on activated carbon 、 水 、 氢气 、 溴 、 铁粉 、 sodium hydride 、 copper(II) sulfate 、 溶剂黄146 、 二乙胺 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 160.0 ℃ 、1.03 MPa 条件下， 反应 58.0h， 生成 tert-butyl 4-[(trifluoromethane)sulfonyloxy]-1H,2H,3H-pyrrolo[2,3-c]pyridine-1-carboxylate
  参考文献：
  名称：

  Azaindolines: derisking the indoline structural alert

  摘要：

  4-Substitued azaindolines, which are isosteres of indolines, are useful synthetic building blocks that reduce the risk of bioactivation induced idiosyncratic toxicity have been prepared. Multigram routes to 2,3-dihydro-1H-pyrrolo[2,3-c]pyridine-4-triflate 16, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-4-carbonitrite 20 and 4-chloro-2,3-dihydro-1H-pyrrolo[2,3-d]pyridazine 30 are outlined. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2011.11.070

文献信息

• NAPHTHYRIDINES AS INHIBITORS OF HPK1
  申请人：Genentech, Inc.

  公开号：US20180282328A1

  公开（公告）日：2018-10-04

  Naphthyridine compounds and their use as inhibitors of HPK1 are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the naphthyridine compounds.

  萘啶化合物及其作为HPK1抑制剂的用途被描述。这些化合物在治疗HPK1依赖性疾病和增强免疫反应方面很有用。还描述了抑制HPK1的方法、治疗HPK1依赖性疾病的方法、增强免疫反应的方法以及制备萘啶化合物的方法。
• ISOQUINOLINES AS INHIBITORS OF HPK1
  申请人：Genentech, Inc.

  公开号：US20180282282A1

  公开（公告）日：2018-10-04

  Isoquinoline compounds and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibitng HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the isoquinoline compounds.

  描述了异喹啉化合物及其作为HPK1（造血激酶1）抑制剂的用途。这些化合物在治疗依赖于HPK1的疾病和增强免疫应答方面非常有用。还描述了抑制HPK1的方法、治疗依赖于HPK1的疾病的方法、增强免疫应答的方法，以及制备异喹啉化合物的方法。
• Naphthyridines as inhibitors of HPK1
  申请人：Genentech, Inc.

  公开号：US10407424B2

  公开（公告）日：2019-09-10

  Naphthyridine compounds and their use as inhibitors of HPK1 are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the naphthyridine compounds.

  介绍了萘啶类化合物及其作为 HPK1 抑制剂的用途。这些化合物可用于治疗 HPK1 依赖性疾病和增强免疫反应。还描述了抑制 HPK1 的方法、治疗 HPK1 依赖性疾病的方法、增强免疫反应的方法以及制备萘啶化合物的方法。
• Azaindolines: derisking the indoline structural alert
  作者：Eugene L. Piatnitski Chekler、Taukeer A. Khan、Rajanikanth Mamidala、James T. Anderson、Raghuram S. Tangirala、Patrick R. Verhoest、Adam M. Gilbert

  DOI：10.1016/j.tetlet.2011.11.070

  日期：2012.1

  4-Substitued azaindolines, which are isosteres of indolines, are useful synthetic building blocks that reduce the risk of bioactivation induced idiosyncratic toxicity have been prepared. Multigram routes to 2,3-dihydro-1H-pyrrolo[2,3-c]pyridine-4-triflate 16, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-4-carbonitrite 20 and 4-chloro-2,3-dihydro-1H-pyrrolo[2,3-d]pyridazine 30 are outlined. (C) 2011 Elsevier Ltd. All rights reserved.
• 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile Derivatives as Potent and Tissue Selective Androgen Receptor Modulators
  作者：Eugene L. Piatnitski Chekler、Rayomond Unwalla、Taukeer A. Khan、Raghuram S. Tangirala、Mark Johnson、Michael St. Andre、James T. Anderson、Thomas Kenney、Sue Chiparri、Chris McNally、Edward Kilbourne、Catherine Thompson、Sunil Nagpal、Gregory Weber、Scott Schelling、Jane Owens、Carl A. Morris、Dennis Powell、Patrick R. Verhoest、Adam M. Gilbert

  DOI：10.1021/jm401625b

  日期：2014.3.27

  We present a novel series of selective androgen receptor modulators (SARMs) which shows excellent biological activity and physical properties. 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)-indoline-4-carbonitriles showed potent binding to the androgen receptor (AR) and activated AR-mediated transcription in vitro. Representative compounds demonstrated diminished activity in promoting the intramolecular interaction between the AR carboxyl (C) and amino (N) termini. This N/C-termini interaction is a biomarker assay for the undesired androgenic responses in vivo. In orchidectomized rats, daily administration of a lead compound from this series showed anabolic activity by increasing levator ani muscle weight. Importantly, minimal androgenic effects (increased tissue weights) were observed in the prostate and seminal vesicles, along with minimal repression of circulating luteinizing hormone (LH) levels and no change in the lipid and triglyceride levels. This lead compound completed a two week rat toxicology study, and was well tolerated at doses up to 100 mg/kg/day, the highest dose tested, for 14 consecutive days.