5-(5-(5-aminopyridin-3-yl)thiophen-2-yl)-2-methylisoindolin-1-one | 1567836-37-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 5-(5-(5-aminopyridin-3-yl)thiophen-2-yl)-2-methylisoindolin-1-one
• 英文别名: 5-(5-(5-Aminopyridin-3-yl)thiophen-2-yl)-2-methylisoindolin-1-one；5-[5-(5-aminopyridin-3-yl)thiophen-2-yl]-2-methyl-3H-isoindol-1-one
• CAS: 1567836-37-6
• 化学式: C₁₈H₁₅N₃OS
• 分子量: 321.403
• InChiKey: GGMQWLJFNYCYTL-UHFFFAOYSA-N

物化性质

• 熔点：
  244-248 °C(Solvent: Methanol ; Dichloromethane)
• 沸点：
  615.8±55.0 °C(Predicted)
• 密度：
  1.330±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  87.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(5-(5-aminopyridin-3-yl)thiophen-2-yl)-2-methylisoindolin-1-one 在 吡啶 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 N-(5-(5-(2-methyl-1-oxoisoindolin-5-yl)thiophen-2-yl)pyridin-3-yl)thiophene-2-sulfonamide sodium salt
  参考文献：
  名称：

  Substituted arylsulphonamides as inhibitors of perforin-mediated lysis

  摘要：

  The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore forming protein perforin have been explored. Perforin is a key component of the human immune response, however inappropriate activity has also been implicated in certain auto-immune and therapy induced conditions such as allograft rejection and graft versus host disease. Since perforin is expressed exclusively by cells of the immune system, inhibition of this protein would be a highly selective strategy for the immunosuppressive treatment of these disorders. Compounds from this series were demonstrated to be potent inhibitors of the lytic action of both isolated recombinant perforin and perforin secreted by natural killer cells in vitro. Several potent and soluble examples were assessed for in vivo pharmacokinetic properties and found to be suitable for progression to an in vivo model of transplant rejection. (C) 2017 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.05.048
• 作为产物：
  描述：

  4-溴-2-甲基苯甲酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 N-溴代丁二酰亚胺(NBS) 、 N-碘代丁二酰亚胺 、 偶氮二异丁腈 、 硫酸 、 氨 、 sodium hydride 、 sodium carbonate 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 、 甲苯 、 苯 为溶剂， 反应 73.5h， 生成 5-(5-(5-aminopyridin-3-yl)thiophen-2-yl)-2-methylisoindolin-1-one
  参考文献：
  名称：

  [EN] PERFORIN INHIBITING BENZENESULFONAMIDE COMPOUNDS, PREPARATION AND USES THEREOF
  [FR] COMPOSÉS DE BENZÈNESULFONAMIDE INHIBITEURS DE LA PERFORINE, LEUR PRÉPARATION ET LEURS UTILISATIONS

  摘要：

  公式（la）的化合物及其药学上可接受的盐、溶剂化合物和水合物，以及相关的调节细胞上穿孔素活性的方法：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至少包含N、O或S中的一种杂原子；芳基、环烷基、杂芳基或杂环烷基环可以选择地被1至3个取代基取代，所述取代基选自卤素、硝基、-C1-Ce烷基、-C1-Ceamino烷基、-C1-C6羟基烷基、-卤代C1-C6烷基、-C1-C6烷氧基、-卤代C1-C6烷氧基、杂芳基、芳基、羟基、-C(0)Ci-C6烷基、-OC(0)Ci-C6烷基、-CH2OC(O)CrC6烷基、-C(O)OC1,-C6烷基、-NHC(O)C1,-C6烷基、-NHS(O)2C1-C6烷基、-S(O)2C1-C6烷基、-S(O)2NH2和-C(O)NJJ；环B是6-10成员芳基或5-6成员杂芳基，其中至少包含N、O或S中的一种杂原子；芳基或杂芳基可以选择地被一个或多个取代基取代，所述取代基选自-NJJ、-OJ、卤素、C1-C6烷基、卤代C1-C6烷基、C1-C6烷氧基、卤代C1-C6烷氧基和-C(0)NJJ；环C选自5-10成员杂芳基或5-10成员杂环烯，每个环至少包含N、S和O中的一种杂原子；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，其中至少包含N或O中的一种杂原子；L是从支链和非支链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-中选取的连接物；其中环B和C，以及环C和D，通过各自环上任何可用的C原子之一的C-C键连接在一起；每次出现的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代C1-C6烷基。

  公开号：

  WO2014028968A1

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
• Benzenesulphonamide inhibitors of the cytolytic protein perforin
  作者：Julie A. Spicer、Christian K. Miller、Patrick D. O'Connor、Jiney Jose、Kristiina M. Huttunen、Jagdish K. Jaiswal、William A. Denny、Hedieh Akhlaghi、Kylie A. Browne、Joseph A. Trapani

  DOI：10.1016/j.bmcl.2016.12.057

  日期：2017.2

  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.
• US9896443B2
  申请人：——

  公开号：US9896443B2

  公开（公告）日：2018-02-20
• Substituted arylsulphonamides as inhibitors of perforin-mediated lysis
  作者：Julie A. Spicer、Christian K. Miller、Patrick D. O'Connor、Jiney Jose、Kristiina M. Huttunen、Jagdish K. Jaiswal、William A. Denny、Hedieh Akhlaghi、Kylie A. Browne、Joseph A. Trapani

  DOI：10.1016/j.ejmech.2017.05.048

  日期：2017.9

  The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore forming protein perforin have been explored. Perforin is a key component of the human immune response, however inappropriate activity has also been implicated in certain auto-immune and therapy induced conditions such as allograft rejection and graft versus host disease. Since perforin is expressed exclusively by cells of the immune system, inhibition of this protein would be a highly selective strategy for the immunosuppressive treatment of these disorders. Compounds from this series were demonstrated to be potent inhibitors of the lytic action of both isolated recombinant perforin and perforin secreted by natural killer cells in vitro. Several potent and soluble examples were assessed for in vivo pharmacokinetic properties and found to be suitable for progression to an in vivo model of transplant rejection. (C) 2017 The Authors. Published by Elsevier Masson SAS.
• [EN] PERFORIN INHIBITING BENZENESULFONAMIDE COMPOUNDS, PREPARATION AND USES THEREOF<br/>[FR] COMPOSÉS DE BENZÈNESULFONAMIDE INHIBITEURS DE LA PERFORINE, LEUR PRÉPARATION ET LEURS UTILISATIONS
  申请人：PETER MACCALLUM CANCER INST

  公开号：WO2014028968A1

  公开（公告）日：2014-02-27

  Compounds of formula (la) 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, -C1-Cealkyl, -C1-Ceaminoalkyl, -C1-C6hydroxyalkyl, -haloC1-C6alkyl, -C1- C6alkoxyl, -haloC1-C

  公式（la）的化合物及其药学上可接受的盐、溶剂化合物和水合物，以及相关的调节细胞上穿孔素活性的方法：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至少包含N、O或S中的一种杂原子；芳基、环烷基、杂芳基或杂环烷基环可以选择地被1至3个取代基取代，所述取代基选自卤素、硝基、-C1-Ce烷基、-C1-Ceamino烷基、-C1-C6羟基烷基、-卤代C1-C6烷基、-C1-C6烷氧基、-卤代C1-C6烷氧基、杂芳基、芳基、羟基、-C(0)Ci-C6烷基、-OC(0)Ci-C6烷基、-CH2OC(O)CrC6烷基、-C(O)OC1,-C6烷基、-NHC(O)C1,-C6烷基、-NHS(O)2C1-C6烷基、-S(O)2C1-C6烷基、-S(O)2NH2和-C(O)NJJ；环B是6-10成员芳基或5-6成员杂芳基，其中至少包含N、O或S中的一种杂原子；芳基或杂芳基可以选择地被一个或多个取代基取代，所述取代基选自-NJJ、-OJ、卤素、C1-C6烷基、卤代C1-C6烷基、C1-C6烷氧基、卤代C1-C6烷氧基和-C(0)NJJ；环C选自5-10成员杂芳基或5-10成员杂环烯，每个环至少包含N、S和O中的一种杂原子；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，其中至少包含N或O中的一种杂原子；L是从支链和非支链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-中选取的连接物；其中环B和C，以及环C和D，通过各自环上任何可用的C原子之一的C-C键连接在一起；每次出现的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代C1-C6烷基。