2-氧代-1,2-二氢苯并[cd]吲哚-6-磺酰氯 | 78078-92-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 2-氧代-1,2-二氢苯并[cd]吲哚-6-磺酰氯
• 英文名称: 2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonyl chloride
• 英文别名: 2-oxo-1,2-dihydrobenz[cd]indol-6-sulfonyl chloride；2-Oxo-benzoindolin-6-sulfochlorid；2-oxo-1H-benzo[cd]indole-6-sulfonyl chloride
• CAS: 78078-92-9
• 化学式: C₁₁H₆ClNO₃S
• mdl: MFCD02732837
• 分子量: 267.693
• InChiKey: HBGOGAFJKXIXKJ-UHFFFAOYSA-N

物化性质

• 沸点：
  338.3±21.0 °C(Predicted)
• 密度：
  1.631±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933790090

反应信息

• 作为反应物：
  描述：

  2-氧代-1,2-二氢苯并[cd]吲哚-6-磺酰氯 在 氨 作用下， 以 四氢呋喃 为溶剂， 以79%的产率得到2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide
  参考文献：
  名称：

  Virtual screening, selection and development of a benzindolone structural scaffold for inhibition of lumazine synthase

  摘要：

  Virtual screening of a library of commercially available compounds versus the structure of Mycobacterium tuberculosis lumazine synthase identified 2-(2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)acetic acid ( 9) as a possible lead compound. Compound 9 proved to be an effective inhibitor of M. tuberculosis lumazine synthase with a K-i of 70 mu M. Lead optimization through replacement of the carboxymethylsulfonamide sidechain with sulfonamides substituted with alkyl phosphates led to a four-carbon phosphate 38 that displayed a moderate increase in enzyme inhibitory activity (K-i 38 mu M). Molecular modeling based on known lumazine synthase/inhibitor crystal structures suggests that the main forces stabilizing the present benzindolone/enzyme complexes involve pi-pi stacking interactions with Trp27 and hydrogen bonding of the phosphates with Arg128, the backbone nitrogens of Gly85 and Gln86, and the side chain hydroxyl of Thr87. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.03.072
• 作为产物：
  描述：

  N-羟基-1,8-萘二甲酰亚胺 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 硝酸 、 溶剂黄146 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 6.0h， 生成 2-氧代-1,2-二氢苯并[cd]吲哚-6-磺酰氯
  参考文献：
  名称：

  Design, synthesis and biological evaluation of naphthostyril derivatives as novel protein kinase FGFR1 inhibitors

  摘要：

  New class of FGFR1 kinase inhibitors with naphthostyril heterocycle has been identified. A series of N-phenylnaphthostyril-1-sulfonamides has been synthesized and tested in vitro. It was revealed that the most active compound N-(4-hydroxyphenyl)naphthostyril-1-sulfonamide inhibited FGFR1 with IC50 of 2 mu M. In our preliminary studies, N-phenylnaphthostyril-1-sulfonamides demonstrated selectivity of FGFR1 inhibition and antiproliferative activity on cancer cell line. N-phenylnaphthostyril-1-sulfonamides have a good potential for further development as anticancer agents.

  DOI：

  10.3109/14756366.2014.895718

文献信息

• [EN] TARGETED BIFUNCTIONAL DEGRADERS<br/>[FR] AGENTS DE DÉGRADATION BIFONCTIONNELS CIBLÉS
  申请人：UNIV YALE

  公开号：WO2021072269A1

  公开（公告）日：2021-04-15

  The present invention provides, in one aspect, bifunctional compounds that can be used to promote or enhance degradation of certain circulating proteins. In another aspect, the present invention provides bifunctional compounds that can be used to promote or enhance degradation of certain autoantibodies. In certain embodiments, treatment or management of a disease and/or disorder requires degradation, removal, or reduction in concentration of the circulating protein or the autoantibody in the subject. Thus, in certain embodiments, administration of a compound of the invention to the subject removes or reduces the circulation concentration of the circulating protein or the autoantibody, thus treating, ameliorating, or preventing the disease and/or disorder. In certain embodiments, the circulating protein is TNF.

  本发明在一个方面提供了可以用来促进或增强降解某些循环蛋白的双功能化合物。在另一个方面，本发明提供了可以用来促进或增强降解某些自身抗体的双功能化合物。在某些实施方式中，治疗或管理疾病和/或疾病需要降解、去除或减少受试者体内循环蛋白或自身抗体的浓度。因此，在某些实施方式中，将本发明的化合物给予受试者可去除或减少循环蛋白或自身抗体的循环浓度，从而治疗、改善或预防疾病和/或疾病。在某些实施方式中，循环蛋白是TNF。
• Design, synthesis and biological evaluation of benzo[cd]indol-2(1H)-ones derivatives as BRD4 inhibitors
  作者：Yuxin Feng、Senhao Xiao、Yantao Chen、Hao Jiang、Na Liu、Cheng Luo、Shijie Chen、Hua Chen

  DOI：10.1016/j.ejmech.2018.04.048

  日期：2018.5

  with benzo [cd]indol-2(1H)-one scaffold was identified as an effective BRD4 inhibitor through the AlphaScreen-based high-throughput screening and its high-resolution crystal structure with BRD4_BD1 protein. A series of 48 compounds were designed and synthesized by structural optimization on compound 1. All the compounds have been evaluated for their BRD4 inhibitory activities. The results showed that

  通过基于AlphaScreen的高通量筛选及其带有BRD4_BD1蛋白的高分辨率晶体结构，将带有苯并[cd] indol-2（1H）-一个骨架的化合物1鉴定为有效的BRD4抑制剂。通过对化合物1进行结构优化，设计并合成了48种化合物。已对所有化合物的BRD4抑制活性进行了评估。结果表明，化合物23、24、28和44是最有潜力的化合物，IC50值分别为1.02μM，1.43μM，1.55μM和3.02μM。根据它们与BRD4_BD1结合的共晶体结构和蛋白质热位移分析，结合模式显示出额外的间接氢键和疏水相互作用使这四种化合物对BRD4的活性高于1。此外，化合物1 选择23和44来​​评估其对MLL-AF4表达的急性白血病细胞系（MV4-11），其他癌细胞系（MDA-MB-231，A549、22Rv1）和非癌细胞系的抗增殖活性（HUV-EC-C，MRC5，RPTEC）。结果表明，这些化合物对MV
• Discovery of Benzo[<i>cd</i>]indol-2(1<i>H</i>)-ones as Potent and Specific BET Bromodomain Inhibitors: Structure-Based Virtual Screening, Optimization, and Biological Evaluation
  作者：Xiaoqian Xue、Yan Zhang、Zhaoxuan Liu、Ming Song、Yanli Xing、Qiuping Xiang、Zhen Wang、Zhengchao Tu、Yulai Zhou、Ke Ding、Yong Xu

  DOI：10.1021/acs.jmedchem.5b01511

  日期：2016.2.25

  The discovery of inhibitors of bromodomain and extra terminal domain (BET) has achieved great progress, and at least seven inhibitors have progressed into clinical trials for the treatment of cancer or inflammatory diseases. Here, we describe the identification, optimization, and evaluation of benzo[cd]indol-2(1H)-one containing compounds as a new class of BET bromodomain inhibitors, starting from

  溴结构域和额外末端结构域（BET）抑制剂的发现已取得很大进展，并且至少有七种抑制剂已进入用于治疗癌症或炎性疾病的临床试验。在这里，我们从基于结构的虚拟筛选（SBVS）开始，介绍作为一类新的BET溴结构域抑制剂的含苯并[ cd ] indol-2（1 H）-一的化合物的鉴定，优化和评估。通过基于结构的优化，可获得具有显着改善的活性的有效化合物。两种最有效的化合物与BRD4溴结构域结合，K d值为124和137 nM。选择的化合物相对于其他非BET亚家族成员表现出高选择性。值得注意的是85显示对MV4; 11白血病细胞具有合理的抗增殖作用，并具有良好的药代动力学特征，口服生物利用度高（75.8％），半衰期适中（T 1/2 = 3.95 h）。所得的铅分子85代表一种新的，有效的和选择性的BET溴结构域抑制剂类，用于开发治疗癌症和炎性疾病的疗法。
• ALTERNATE MORPHEEIN FORMS OF ALLOSTERIC PROTEINS AS A TARGET FOR THE DEVELOPMENT OF BIOACTIVE MOLECULES
  申请人：Jaffe Eileen K.

  公开号：US20090048324A1

  公开（公告）日：2009-02-19

  A composition having an agent adapted to affect a multimeric protein by binding to a binding site of the multimeric protein and thereby affecting an equilibrium of units, wherein the multimeric protein has an assembly having a plurality of said units, wherein each of the units has a first complementary surface and a second complementary surface and wherein the first complementary surface of one unit is associated with the second complementary surface of another unit, provided that the assembly is at least one of different quaternary isoforms on a condition that in the multimeric protein (1) a structure of each of the units determines a structure of the different quaternary isoforms, (2) the units are in the equilibrium and (3) the structure of the different quaternary isoforms influences a function of the multimeric protein.

  一种组合物，具有适用于影响多聚蛋白的药剂，通过结合多聚蛋白的结合位点并因此影响单位的平衡，其中多聚蛋白具有具有多个该单位的组装体，其中每个单位具有第一互补表面和第二互补表面，其中一个单位的第一互补表面与另一个单位的第二互补表面相关联，前提是组装体至少是不同的四聚体异构体之一，在多聚蛋白中（1）每个单位的结构决定不同四聚体异构体的结构，（2）单位处于平衡状态，（3）不同四聚体异构体的结构影响多聚蛋白的功能。
• Alternate morpheein forms of allosteric proteins as a target for the development of bioactive molecules
  申请人：Fox Chase Cancer Center

  公开号：US08153410B2

  公开（公告）日：2012-04-10

  A composition having an agent adapted to affect a multimeric protein by binding to a binding site of the multimeric protein and thereby affecting an equilibrium of units, wherein the multimeric protein has an assembly having a plurality of said units, wherein each of the units has a first complementary surface and a second complementary surface and wherein the first complementary surface of one unit is associated with the second complementary surface of another unit, provided that the assembly is at least one of different quaternary isoforms on a condition that in the multimeric protein (1) a structure of each of the units determines a structure of the different quaternary isoforms, (2) the units are in the equilibrium and (3) the structure of the different quaternary isoforms influences a function of the multimeric protein.

  该组合物具有适于影响多聚蛋白的剂，通过结合多聚蛋白的结合位点，从而影响单元的平衡，其中多聚蛋白具有具有多个单元的组装体，其中每个单元具有第一互补表面和第二互补表面，并且其中一个单元的第一互补表面与另一个单元的第二互补表面相关联，前提是组装体至少是不同的四聚体亚型之一，在多聚蛋白中（1）每个单元的结构确定不同四聚体亚型的结构，（2）单元处于平衡状态，（3）不同四聚体亚型的结构影响多聚蛋白的功能。