chromanol 293B | 163163-24-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: chromanol 293B
• 英文别名: trans-6-cyano-4-(N-ethylsulphonyl-N-methylamino)-3-hydroxy-2,2-dimethyl-chromane；N-(6-cyano-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl)-N-methylethanesulfonamide
• CAS: 163163-24-4
• 化学式: C₁₅H₂₀N₂O₄S
• 分子量: 324.401
• InChiKey: HVSJHHXUORMCGK-UHFFFAOYSA-N

物化性质

• 熔点：
  192 °C
• 沸点：
  474.1±55.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：18 毫克/毫升

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  99
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R20/21/22
• WGK Germany：
  3
• 安全说明：
  S36/37,S7/9

反应信息

• 作为产物：
  描述：

  N-methyl-ethanesulfonamide 、 3,4-epoxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile 在 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 反应 0.33h， 生成 chromanol 293B
  参考文献：
  名称：

  Synthesis and Activity of Novel and Selective I_Ks-Channel Blockers

  摘要：

  Since the discovery of the I-Ks-potassium channel as the slowly activating component of the delayed rectifier current (I-k) in cardiac tissue, the search for blockers of this current has been intense. During the screening of K-ATP-channel openers of the chromanol type we found that chromanol 293B was able to block I-Ks. Chromanol 293B is a sulfonamide analogue of the K-ATP-channel openers but had no activity on this target. Experiments were initiated to improve the activity and properties based on this lead compound. As a screening model we used Xenopus oocytes injected with human minK (KCNE1). Variations of the aromatic substituent and the sulfonamide group were prepared, and their activity was evaluated. We found that the greatest influence on activity was found in the aromatic substituents. The most active compounds were alkoxy substituted. We chose HMR1556 ((3R, 4S)-(+)-N-[-3-hydroxy-2,2-dimethyl-6-(4,4,4-trifluorobutoxy)chroman-4-yl]-N-methyl-ethanesulfonamide) 10a for development as an antiarrhythmic drug. The absolute configuration, resulting from an X-ray single-crystal structure analysis, was determined.

  DOI：

  10.1021/jm0109255

文献信息

• [EN] GPBP-1 INHIBITION AND ITS THERAPEUTIC USE<br/>[FR] INHIBITION DE GPBP-1 ET SON UTILISATION THÉRAPEUTIQUE
  申请人：FIBROSTATIN S L

  公开号：WO2014006020A1

  公开（公告）日：2014-01-09

  The present invention provides compositions including anti-tumor agents and inhibitors of Goodpasture antigen binding protein, p21, and ABCC7, and their use in treating cancer.

  本发明提供了包括抗肿瘤剂和Goodpasture抗原结合蛋白、p21和ABCC7的抑制剂的组合物，并将其用于治疗癌症。
• GPBP-1 inhibition and its therapeutic use
  申请人：Flbrostatin S.L.

  公开号：US20140005134A1

  公开（公告）日：2014-01-02

  The present invention provides compositions including anti-tumor agents and inhibitors of Goodpasture antigen binding protein, p21, and ABCC7, and their use in treating cancer.

  本发明提供了包括抗肿瘤药物和Goodpasture抗原结合蛋白、p21和ABCC7的抑制剂在内的组合物，并且这些组合物可用于治疗癌症。
• Sulfonamid-substituierte Chromane mit Kaliumkanal blockierender Wirkung
  申请人：HOECHST AKTIENGESELLSCHAFT

  公开号：EP0860440A1

  公开（公告）日：1998-08-26

  Chromane der Formel I mit den im Anspruch 1 angegebenen Bedeutungen von R(A), R(B) und R(1) bis R(8) sind hervorragend geeignet zum Herstellen eines Medikaments zum Blockieren des K+ Kanal, der durch cyclisches Adenosinmonophosphat (cAMP) geöffnet wird; ferner zum Herstellen eines Medikaments zum Inhibieren Magensäuresekretion; zur Behandlung von Ulcera des Magens und des intestinalen Bereiches, insbesondere des Duodenums, zur Behandlung der Refluxoesophagitis, zur Behandlung von Durchfall-Erkrankungen, zur Behandlung und Verhinderung aller Typen von Arrhythmien einschließlich atrialer, ventrikulärer und supraventrikulärer Arrhythmien, sowie zur Kontrolle von Reentry-Arrhythmien und zur Verhinderung des plötzlichen Herztodes infolge von Kammerflimmerns.

  如权利要求 1 所定义的具有 R(A)、R(B) 具有权利要求1中定义的R(A)、R(B)和R(1)至R(8)含义的色甘酸盐是制造阻断由环磷酸腺苷（cAMP）打开的K+通道的药物的极佳原料；也是制造抑制胃酸分泌的药物的极佳原料； 用于治疗胃和肠道溃疡，特别是十二指肠溃疡，治疗反流性食道炎，治疗腹泻病，治疗和预防各种类型的心律失常，包括房性、室性和室上性心律失常，以及控制再入型心律失常和预防心室颤动引起的心脏性猝死。
• Treatment of neurological and neurodevelopmental diseases and disorders associated with aberrant ion channel expression and activity
  申请人：LIEBER INSTITUTE FOR BRAIN DEVELOPMENT

  公开号：US11221329B2

  公开（公告）日：2022-01-11

  Provided are methods for treating and/or reducing the symptoms of a neurological or neurodevelopmental disease or disorder characterized by ectopic expression of certain ion channels, in particular, the Nav1.8 subtype SCN10a sodium channel, or the KCNQ1 potassium channel, in neuronal cells of the central nervous system (CNS) of a subject by administering to a subject in need an antagonist of one or both of these ion channels, and in particular, an antagonist of SCN10a, to block, reduce, or suppress the aberrant CNS neuronal ion channel expression and/or activity and normalize behavioral and cognitive defects associated with the neurological and neurodevelopmental disease or disorder, so as to treat and/or reduce the symptoms of the neurological or neurodevelopmental disease or disorder. Examples of such diseases or disorders that may be treated by the described methods include, for example, Pitt-Hopkins Syndrome (PTHS), autism, autism spectrum disorder, schizophrenia, 18q syndrome and the like.

  本发明提供了用于治疗和/或减轻神经或神经发育疾病或紊乱症状的方法，该疾病或紊乱的特征是某些离子通道的异位表达，特别是 Nav1.8 亚型 SCN10a 钠通道或 KCNQ1 钾通道在中枢神经系统（CNS）神经细胞中的异位表达。8亚型SCN10a钠通道或KCNQ1钾通道的方法，该方法通过向有需要的受试者施用一种或两种这些离子通道的拮抗剂，特别是SCN10a的拮抗剂，以阻断、减少或抑制异常的中枢神经系统（CNS）离子通道、或抑制异常的中枢神经系统神经元离子通道表达和/或活性，使与神经系统和神经发育疾病或紊乱相关的行为和认知缺陷正常化，从而治疗和/或减轻神经系统或神经发育疾病或紊乱的症状。可通过所述方法治疗的此类疾病或紊乱的例子包括皮特-霍普金斯综合征（PTHS）、自闭症、自闭症谱系障碍、精神分裂症、18q 综合征等。
• Use of inhibitors of the KQT1 channel and methods of controlling and treating diseases caused by helminths and ectoparasites
  申请人：Aventis Pharma Deutschland GMBH

  公开号：US20020055537A1

  公开（公告）日：2002-05-09

  Use of inhibitors of the KQT1 channel for preparing a medicament for treating diseases caused by helminths and ectoparasites Inhibitors of the KQT1 channel are a novel way of destroying helminths and ectoparasites. For this reason, blockers of the cellular KQT1 channel, which is present in helminths and ectoparasites, are used for preparing a medicament for the treatment of vertebrates and humans infested by helminths or ectoparasites. These KQT1 blockers are used as medicaments on their own or in combination with other medicaments and therapeutic measures. Inhibitors of the KQT1 channel are likewise a novel mechanism of action for phytoparasites such as insects, arachnids, molluscs and nematodes, and consequently, they are used for preparing a crop protection composition.

  使用 KQT1 通道抑制剂制备治疗蠕虫和体外寄生虫引起的疾病的药物 KQT1 通道抑制剂是消灭蠕虫和体外寄生虫的一种新方法。因此，蠕虫和体外寄生虫体内的细胞 KQT1 通道阻断剂可用于制备治疗脊椎动物和人类蠕虫或体外寄生虫疾病的药物。这些 KQT1 阻断剂可单独用作药物，也可与其他药物和治疗措施结合使用。 KQT1 通道抑制剂同样也是一种针对植物寄生虫（如昆虫、蛛形纲动物、软体动物和线虫）的新型作用机制，因此可用于制备作物保护组合物。