1-甲基苯并咪唑-5-磺酰氯 | 923034-28-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 1-甲基苯并咪唑-5-磺酰氯
• 英文名称: 1-methyl-1H-benzo[d]imidazole-5-sulfonyl chloride
• 英文别名: 1-methyl-1H-1,3-benzodiazole-5-sulfonyl chloride；1-methylbenzimidazole-5-sulfonyl chloride
• CAS: 923034-28-0
• 化学式: C₈H₇ClN₂O₂S
• mdl: MFCD19200528
• 分子量: 230.675
• InChiKey: OOPRJSVWFDUCQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  60.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-甲基苯并咪唑-5-磺酰氯 、 2-氨基-5-乙酰基吡啶 在 吡啶 作用下， 反应 1.0h， 生成
  参考文献：
  名称：

  α-Mercaptoketone based histone deacetylase inhibitors

  摘要：

  In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel alpha-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, alpha-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.058
• 作为产物：
  描述：

  C₈H₈N₂S 在 水 、 氯 作用下， 以 四氯化碳 为溶剂， 反应 0.83h， 以85%的产率得到1-甲基苯并咪唑-5-磺酰氯
  参考文献：
  名称：

  Multicyclic sulfonamide compounds as inhibitors of histone deacetylase for the treatment of disease

  摘要：

  本文披露了如下所述的Formula VII的磺胺类化合物。本文还披露了用于治疗疾病状态的方法和组合物，包括但不限于癌症、自身免疫疾病、组织损伤、中枢神经系统疾病、神经退行性疾病、纤维化、骨疾病、多聚谷氨酰胺重复疾病、贫血、地中海贫血、炎症症状、心血管疾病以及血管生成在发病机制中起作用的疾病，使用本发明的化合物。此外，还披露了调节组蛋白去乙酰化酶（HDAC）活性的方法。

  公开号：

  US20070027184A1

文献信息

• The Discovery and Hit-to-Lead Optimization of Tricyclic Sulfonamides as Potent and Efficacious Potentiators of Glycine Receptors
  作者：Howard Bregman、Jeffrey R. Simard、Kristin L. Andrews、Shawn Ayube、Hao Chen、Hakan Gunaydin、Angel Guzman-Perez、Jiali Hu、Liyue Huang、Xin Huang、Paul H. Krolikowski、Sonya G. Lehto、Richard T. Lewis、Klaus Michelsen、Pamela Pegman、Matthew H. Plant、Paul L. Shaffer、Yohannes Teffera、Shuyan Yi、Maosheng Zhang、Jacinthe Gingras、Erin F. DiMauro

  DOI：10.1021/acs.jmedchem.6b01496

  日期：2017.2.9

  Current pain therapeutics suffer from undesirable psychotropic and sedative side effects, as well as abuse potential. Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels expressed in nerves of the spinal dorsal horn, where their activation is believed to reduce transmission of painful stimuli. Herein, we describe the identification and hit-to-lead optimization of a novel class of tricyclic sulfonamides as allosteric GlyR potentiators. Initial optimization of high-throughput screening (HTS) hit 1 led to the identification of 3, which demonstrated ex vivo potentiation of glycine-activated current in mouse dorsal horn neurons from spinal cord slices. Further improvement of potency and pharmacokinetics produced in vivo proof-of-concept tool molecule 20 (AM-1488), which reversed tactile allodynia in a mouse spared-nerve injury (SNI) model. Additional structural optimization provided highly potent potentiator 32 (AM-3607), which was cocrystallized with human GlyR alpha 3(cryst) to afford the first described potentiator-bound X-ray cocrystal structure within this class of ligand-gated ion channels (LGICs).
• Applications of parallel synthetic lead hopping and pharmacophore-based virtual screening in the discovery of efficient glycine receptor potentiators
  作者：Nagasree Chakka、Kristin L. Andrews、Loren M. Berry、Howard Bregman、Hakan Gunaydin、Liyue Huang、Angel Guzman-Perez、Matthew H. Plant、Jeffrey R. Simard、Jacinthe Gingras、Erin F. DiMauro

  DOI：10.1016/j.ejmech.2017.05.036

  日期：2017.9

  Glycine receptors (GlyRs) are pentameric glycine-gated chloride ion channels that are enriched in the brainstem and spinal cord where they have been demonstrated to play a role in central nervous system (CNS) inhibition. Herein we describe two novel classes of glycine receptor potentiators that have been developed using similarity- and property-guided scaffold hopping enabled by parallel synthesis and pharmacophore-based virtual screening strategies. This effort resulted in the identification of novel, efficient and modular leads having favorable in vitro ADME profiles and high CNS multi-parameter optimization (MPO) scores, exemplified by azetidine sulfonamide 19 and aminothiazole sulfone (ent2)-20. (C) 2017 Elsevier Masson SAS. All rights reserved.
• [EN] MULTICYCLIC SULFONAMIDE COMPOUNDS AS INHIBITORS OF HISTONE DEACETYLASE FOR THE TREATMENT OF DISEASE<br/>[FR] COMPOSÉS DE SULFONAMIDE MULTICYCLIQUE EN TANT QU'INHIBITEURS D'HISTONE DÉACÉTYLASE POUR LE TRAITEMENT DES MALADIES
  申请人：KALYPSYS INC

  公开号：WO2007016354A1

  公开（公告）日：2007-02-08

  [EN] Disclosed herein are sulfonamide compounds of Formula (VII) as described herein. Methods and compositions are disclosed for treating disease states including, but not limited to cancers, autoimmune diseases, tissue damage, central nervous system disorders, neurodegenerative disorders, fibrosis, bone disorders, polyglutamine-repeat disorders, anemias, thalassemias, inflammatory conditions, cardiovascular conditions, and disorders in which angiogenesis play a role in pathogenesis, using the compounds of the invention. In addition, methods of modulating the activity of histone deacetylase (HDAC) are also disclosed.
  [FR] La présente invention concerne les composés de sulfonamide de la Formule (VII) tels que décrits ici. Des procédés et des compositions sont dévoilés pour le traitement d'états de maladie incluant, mais sans s'y limiter, les cancers, les maladies auto-immunes, les détériorations de tissus, les troubles du système nerveux central, les troubles à neurodégénérescence, la fibrose, les troubles osseux, les troubles liés à la répétition de polyglutamine, les anémies, les thalassémies, les maladies inflammatoires, les maladies cardiovasculaires et les troubles dans lesquels l'angiogénèse joue un rôle dans la pathogénèse, en utilisant les composés de l'invention. Par ailleurs, les procédés de modulation de l'activité de l'histone déacétylase (HDAC) sont également dévoilés.
• [EN] INHIBITORS OF HISTONE DEACETYLASE FOR THE TREATMENT OF DISEASE<br/>[FR] INHIBITEURS D'HISTONE DESACETYLASE POUR LE TRAITEMENT DE MALADIES
  申请人：KALYPSYS INC

  公开号：WO2007067993A1

  公开（公告）日：2007-06-14

  [EN] Disclosed herein are compounds of formula I and methods used for treating disease states including, but not limited to cancers, autoimmune diseases, tissue damage, central nervous system disorders, neurodegenerative disorders, fibrosis, bone disorders, polyglutamine- repeat disorders, anemias, thalassemias, inflammatory conditions, cardiovascular conditions, and disorders in which angiogenesis play a role in pathogenesis. In addition, methods of modulating the activity of histone deacetylase (HDAC) are also disclosed.
  [FR] La présente invention concerne des composés et des procédés utilisés pour traiter des états pathologiques comprenant, sans y être limités, des cancers, des maladies auto-immunes, des lésions tissulaires, des troubles du système nerveux central, des maladies neurodégénératives, la fibrose, des troubles osseux, des troubles de répétition de polyglutamine, des anémies, des thalassémies, des états inflammatoires, des troubles cardiovasculaires, et des troubles dans lesquels l'angiogenèse joue un rôle dans la pathogenèse. De plus, la présente invention concerne des procédés de modulation de l'activité de l'histone désacétylase (HDAC).
• α-Mercaptoketone based histone deacetylase inhibitors
  作者：Paul L. Wash、Timothy Z. Hoffman、Brandon M. Wiley、Céline Bonnefous、Nicholas D. Smith、Michael S. Sertic、Charles M. Lawrence、Kent T. Symons、Phan-Manh Nguyen、Kevin D. Lustig、Xin Guo、Tami Annable、Stewart A. Noble、Jeffrey H. Hager、Christian A. Hassig、James W. Malecha

  DOI：10.1016/j.bmcl.2008.10.058

  日期：2008.12

  In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel alpha-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, alpha-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo. (C) 2008 Elsevier Ltd. All rights reserved.