2-甲基-7-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷-2-基)-3,4-二氢异喹啉-1(2H)-酮 | 1313399-69-7

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 中文名称: 2-甲基-7-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷-2-基)-3,4-二氢异喹啉-1(2H)-酮
• 英文名称: 2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinolin-1(2H)-one
• 英文别名: 2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinolin-1-one
• CAS: 1313399-69-7
• 化学式: C₁₆H₂₂BNO₃
• 分子量: 287.167
• InChiKey: IXDPKMFBKRCQQE-UHFFFAOYSA-N

物化性质

• 沸点：
  440.4±45.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.61
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-甲基-7-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷-2-基)-3,4-二氢异喹啉-1(2H)-酮 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 、 溶剂黄146 、 β-丙氨酸 作用下， 以 乙醇 、 水 、 丙酮 、 甲苯 为溶剂， 反应 17.0h， 生成 2-methyl-7-(5-((5-oxo-2-thioxoimidazolidin-4-ylidene)methyl)thiophen-2-yl)-3,4-dihydroisoquinolin-1(2H)-one
  参考文献：
  名称：

  Exploration of a Series of 5-Arylidene-2-thioxoimidazolidin-4-ones as Inhibitors of the Cytolytic Protein Perforin

  摘要：

  A series of novel 5-arylidene-2-thioxoimidazolidin-4-ones were investigated as inhibitors of the lymphocyte-expressed pore-forming protein perform. Structure activity relationships were explored through variation of an isoindolinone or 3,4-dihydroisoquinolinone subunit on a fixed 2-thioxoimidazolidin-4-one/thiophene core. The ability of the resulting compounds to inhibit the lytic activity of both isolated perform protein and perforin delivered in situ by natural killer cells was determined. A number of compounds showed excellent activity at concentrations that were nontoxic to the killer cells, and several were a significant improvement on previous classes of inhibitors, being substantially more potent and soluble. Representative examples showed rapid and reversible binding to immobilized mouse perforin at low concentrations (<= 2.5 mu M) by surface plasmon resonance and prevented formation of perforin pores in target cells despite effective target cell engagement, as determined by calcium influx studies. Mouse PK studies of two analogues showed T-1/2 values of 1.1-1.2 h (dose of 5 mg/kg iv) and MTDs of 60-80 mg/kg (ip).

  DOI：

  10.1021/jm401604x
• 作为产物：
  描述：

  7-溴-3,4-二氢-2H-异喹啉-1-酮 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 sodium hydride 作用下， 以 1,4-二氧六环 、 N,N-二甲基乙酰胺 为溶剂， 反应 3.5h， 生成 2-甲基-7-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷-2-基)-3,4-二氢异喹啉-1(2H)-酮
  参考文献：
  名称：

  [EN] C-GLYCOSIDE COMPOUNDS USEFUL FOR TREATING DISEASE
  [FR] COMPOSÉS C-GLYCOSIDES UTILES POUR TRAITER UNE MALADIE

  摘要：

  本发明涉及一种作为FimH抑制剂有用的甘露糖苷衍生物化合物，以及用于治疗或预防尿路感染的方法。

  公开号：

  WO2017156508A1

文献信息

• COMPOUNDS, PREPARATION AND USES THEREOF
  申请人：Spicer Julie Ann

  公开号：US20130065897A1

  公开（公告）日：2013-03-14

  The present invention provides novel compounds of the Formula I, pharmaceutical compositions comprising such compounds and methods for using such compounds as agents or drugs for inhibiting perforin activity and for treating a subject at risk of or susceptible to a disease or disorder, or having a disease or disorder associated with undesirable perforin activity.

  本发明提供了公式I的新化合物，包括这些化合物的制药组合物以及使用这些化合物作为抑制穿孔素活性的药剂或药物的方法，以及用于治疗处于风险或易感疾病或紊乱，或具有与不良穿孔素活性相关的疾病或紊乱的受试者。
• 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。
• [EN] COMPOUND HAVING KINASE INHIBITORY FUNCTION, AND PREPARATION METHOD THEREFOR AND APPLICATION THEREOF<br/>[FR] COMPOSÉ AYANT UNE FONCTION INHIBITRICE DE KINASE, SON PROCÉDÉ DE PRÉPARATION ET SON APPLICATION<br/>[ZH] 一类具有激酶抑制功能的化合物及其制备和应用
  申请人：ENNOVABIO ZHEJIANG PHARMACEUTICALS CO LTD

  公开号：WO2022253328A1

  公开（公告）日：2022-12-08

  一种HPK1激酶抑制剂及其制备方法和应用。具体地，一种如式(I)所示的化合物，所述的化合物具有HPK1抑制活性，用于制备治疗癌症和其他HPK1活性相关疾病的药物组合物。
• 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.
• WO2020160180A5
  申请人：——

  公开号：WO2020160180A5

  公开（公告）日：2023-02-07