N-(2,4,6-三甲基苯基)-双环[2.2.1]庚烷-2-甲酰胺 | 489402-47-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: N-(2,4,6-三甲基苯基)-双环[2.2.1]庚烷-2-甲酰胺
• 英文名称: N-mesitylbicyclo[2.2.1]heptane-2-carboxamide
• 英文别名: N-(2,4,6-trimethylphenyl)bicyclo[2.2.1]heptane-2-carboxamide
• CAS: 489402-47-3
• 化学式: C₁₇H₂₃NO
• 分子量: 257.37
• InChiKey: SIQGKPGBLYKQBB-UHFFFAOYSA-N

物化性质

• 沸点：
  398.8±11.0 °C(Predicted)
• 密度：
  1.106±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO：可溶5mg/mL，澄清（加热）

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335,H413

制备方法与用途

生物活性

ML213（CID-3111211）是一种选择性的作用于KCNQ2（Kv7.2）和KCNQ4（Kv7.4）钾通道的开放剂，其EC50值分别为230 nM和510 nM。

靶点

• EC50: 230 nM (Kv7.2通道), 510 nM (Kv7.4通道)

体外研究

ML213（100 nM至30 μM）能够增加最大传导性，达到控制值的212% ± 27%，其EC50为0.8 ± 0.3 μM。当浓度为10 μM时，ML213能将Kv7.4电流的去激活速率减少4.6倍，在电压范围从-130 mV至-90 mV内。

ML213对过表达在A7r5细胞中的同源性Kv7.5通道表现出强大的活性。当浓度为10 μM时，ML213能够将Kv7.5通道的最大传导性增加到控制值的0.7 ± 0.2 μM，并平均减少其去激活速率5.9倍。

对于异源性Kv7.4/7.5通道，ML213产生类似的效果：最大传导性增加了204% ± 11%，EC50为1.1 ± 0.6 μM，同时最大负移位达34.2 ± 3.3 mV，其EC50为3.8 ± 1.2 μM。

ML213在不同预收缩的大鼠血管中产生舒张作用。此外，在小肠动脉平滑肌细胞中，10 μM的ML213能引发去极化效应。ML213还表现出浓度依赖性地将KCNQ2激活的半数有效浓度（EC50）向左移动340 ± 70 nM，并达到最大偏移37.4 mV。

文献信息

• [EN] QUINOLINYL-PYRAZINE-CARBOXAMIDE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS DE QUINOLINYL-PYRAZINE-CARBOXAMIDE ET UTILISATIONS ASSOCIÉES
  申请人：UNIV MICHIGAN REGENTS

  公开号：WO2020132459A1

  公开（公告）日：2020-06-25

  This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quinolinyl-pyrazine-carboxamide (or similar) structure which function as activators of the cholesterol biosynthesis pathway within cancer cells and/or immune cells, which function as activators of the cell cycle regulation pathway within cancer cells and/or immune cells, and which function as up-regulators of HMGCS1 protein expression within cancer cells and/or immune cells, and which function as effective therapeutic agents for treating, ameliorating, and preventing various forms of cancer and other inflammatory disease.

  这项发明属于药物化学领域。具体来说，该发明涉及一类新型小分子，其具有喹啉基-吡嗪-羧酰胺（或类似）结构，其在癌细胞和/或免疫细胞内作为胆固醇生物合成途径的激活剂，作为癌细胞和/或免疫细胞内细胞周期调控途径的激活剂，作为癌细胞和/或免疫细胞内HMGCS1蛋白表达的上调剂，以及作为治疗、改善和预防各种癌症和其他炎症性疾病的有效治疗剂。
• METHODS OF TREATING NEUROPSYCHIATRIC DISORDERS
  申请人：UNIVERSITY OF ROCHESTER

  公开号：US20200197445A1

  公开（公告）日：2020-06-25

  The present disclosure is directed to a method of treating a neuropsychiatric disorder. This method involves selecting a subject having the neuropsychiatric disorder and administering to the selected subject a preparation of glial progenitor cells at a dosage effective to treat the neuropsychiatric disorder in the subject. Another aspect of the disclosure is directed to a method of treating a neuropsychiatric disorder that includes selecting a subject having the neuropsychiatric disorder and administering, to the selected subject, a potassium (K + ) channel activator at a dosage effective to restore normal brain interstitial glial K + levels in the selected subject and treat the neuropsychiatric disorder is also disclosed.
• [EN] METHOD OF TREATING KCNQ RELATED DISORDERS<br/>[FR] PROCÉDÉ DE TRAITEMENT DE TROUBLES LIÉS À KCNQ
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2011085351A2

  公开（公告）日：2011-07-14

  The instant invention describes methods of treating KCNQ related diseases and disorders.