tert-butyl (5-(5-(1-methyl-2-oxoindolin-5-yl)thiophen-2-yl)pyridin-3-yl)carbamate | 1567837-72-2

• 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: tert-butyl (5-(5-(1-methyl-2-oxoindolin-5-yl)thiophen-2-yl)pyridin-3-yl)carbamate
• 英文别名: tert-butyl N-[5-[5-(1-methyl-2-oxo-3H-indol-5-yl)thiophen-2-yl]pyridin-3-yl]carbamate
• CAS: 1567837-72-2
• 化学式: C₂₃H₂₃N₃O₃S
• 分子量: 421.52
• InChiKey: QCQGHZKUGQSDBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  99.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (5-(5-(1-methyl-2-oxoindolin-5-yl)thiophen-2-yl)pyridin-3-yl)carbamate 在 吡啶 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 21.0h， 生成 2,4-difluoro-N-(5-(5-(1-methyl-2-oxoindolin-5-yl)thiophen-2-yl)pyridin-3-yl)benzenesulfonamide
  参考文献：
  名称：

  Benzenesulphonamide inhibitors of the cytolytic protein perforin

  摘要：

  The pore-forming protein perforin is a key component of mammalian cell-mediated immunity and essential to the pathway that allows elimination of virus-infected and transformed cells. Perforin activity has also been implicated in certain auto-immune conditions and therapy-induced conditions such as allograft rejection and graft versus host disease. An inhibitor of perforin activity could be used as a highly specific immunosuppressive treatment for these conditions, with reduced side-effects compared to currently accepted therapies. Previously identified first-in-class inhibitors based on a 2-thioxoimidazolidin-4-one core show suboptimal physicochemical properties and toxicity toward the natural killer (NK) cells that secrete perforin in vivo. The current benzenesulphonamide-based series delivers a non-toxic bioisosteric replacement possessing improved solubility. (C) 2017 The Authors. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.12.057
• 作为产物：
  描述：

  1-methyl-5-(thiophen-2-yl)indolin-2-one 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 N-碘代丁二酰亚胺 、 sodium carbonate 作用下， 以 乙醇 、 氯仿 、 溶剂黄146 、 甲苯 为溶剂， 生成 tert-butyl (5-(5-(1-methyl-2-oxoindolin-5-yl)thiophen-2-yl)pyridin-3-yl)carbamate
  参考文献：
  名称：

  Benzenesulphonamide inhibitors of the cytolytic protein perforin

  摘要：

  The pore-forming protein perforin is a key component of mammalian cell-mediated immunity and essential to the pathway that allows elimination of virus-infected and transformed cells. Perforin activity has also been implicated in certain auto-immune conditions and therapy-induced conditions such as allograft rejection and graft versus host disease. An inhibitor of perforin activity could be used as a highly specific immunosuppressive treatment for these conditions, with reduced side-effects compared to currently accepted therapies. Previously identified first-in-class inhibitors based on a 2-thioxoimidazolidin-4-one core show suboptimal physicochemical properties and toxicity toward the natural killer (NK) cells that secrete perforin in vivo. The current benzenesulphonamide-based series delivers a non-toxic bioisosteric replacement possessing improved solubility. (C) 2017 The Authors. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.12.057

文献信息

• PERFORIN INHIBITING BENZENESULFONAMIDE COMPOUNDS, PREPARATION AND USES THEREOF
  申请人：Peter MacCallum Cancer Institute

  公开号：US20150218150A1

  公开（公告）日：2015-08-06

  Compounds of formula (1a) and pharmaceutically acceptable salts, solvates, and hydrates thereof and related methods of modulatin perforin activity on a cell: wherein Ring A is selected from a 6-10 membered aryl, 5-6 membered cycloalkyi, 5-6 membered heteroaryl or 5-6 membered heterocyclyl, wherein the heteroaryl and heterocyclyl rings comprise at least one heteroatom selected from N, O or S; and wherein the aryl, cycloalkyi, heteroaryl or heterocyclyl rings are optionally substituted with 1 to 3 substituents selected from halo, nitro, —C 1 -Cealkyl, —C 1 -Ceaminoalkyl, —C 1 -C 6 hydroxyalkyl, -haloC 1 -C 6 alkyl, —C 1 -C 6 alkoxyl, -haloC 1 —C

  公式（1a）的化合物及其药学上可接受的盐、溶剂化物和水合物，以及相关的调节细胞穿孔素活性的方法：其中环A选自6-10成员芳基、5-6成员环烷基、5-6成员杂芳基或5-6成员杂环烷基，其中杂芳基和杂环烷基环中至少包含一个选自N、O或S的杂原子；环A、环烷基、杂芳基或杂环烷基环可以选择地被1到3个取代基所取代，所述取代基选自卤素、硝基、-C1-Ce烷基、-C1-Ce氨基烷基、-C1-C6羟基烷基、-卤基C1-C6烷基、-C1-C6烷氧基、-卤基C1-C芳烃或5-10成员杂环亚烷，每个环中至少包含一个选自N、S和O的杂原子；环D是可选择地取代的苯并9-11成员杂环烷基或可选择地取代的苯并9-11成员杂芳基，其中至少有一个杂原子选自N或O；L是选择自支链和非支链C1-C4烷基、-S（0）2-NH-、-C（0）-NH-、-NH-C（0）-NH-、-S（0）2-NH-C（0）-NH-、-S（0）2-NH-C（0）-和-CH═CH-的连接体；其中环B和环C以及环C和环D是通过各自环上任何可用的C原子上的C-C键连接在一起的；在每次出现中，J独立地选自H、可选择地取代的C1-C6烷基或可选择地取代的卤基C1-C6烷基。
• US9896443B2
  申请人：——

  公开号：US9896443B2

  公开（公告）日：2018-02-20