5-chloro-N-(5-phenyl-1,3,4-oxadiazol-2-yl)thiophene-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 5-chloro-N-(5-phenyl-1,3,4-oxadiazol-2-yl)thiophene-2-carboxamide
• 化学式: C₁₃H₈ClN₃O₂S
• 分子量: 305.744
• InChiKey: MPMRVGFJURSEGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  96.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氯噻吩-5-甲酸 在 吡啶 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 5.5h， 生成 5-chloro-N-(5-phenyl-1,3,4-oxadiazol-2-yl)thiophene-2-carboxamide
  参考文献：
  名称：

  1,3,4-恶二唑的合成作为选择性T型钙离子通道抑制剂。

  摘要：

  神经性疼痛，癫痫，失眠和震颤症可能是由于T型Ca2 +通道功能异常导致细胞内Ca2 +浓度升高而引起的。因此，T型钙通道可能成为治疗神经性疼痛和癫痫的药物开发目标。通过合理的药物设计方法，合成了一组2,5-二取代的1,3,4-恶二唑分子，并评估了其对选择性T型通道的抑制作用。合成策略由三个反应的简短序列组成：（i）硫代氨基脲与酰氯的缩合；（ii）被1，3-二溴-5，5-二甲基乙内酰脲闭合的环；（iii）与各种酰氯偶联。5-氯-N-（5-苯基-1,3，发现4-恶二唑-2-基）噻吩-2-羧酰胺（11）选择性抑制小鼠背根神经节神经元和/或人胚肾（HEK）-293细胞中Na +和K +通道上的T型Ca2 +通道和在小鼠模型中抑制癫痫发作引起的死亡。因此，化合物11是研究T通道的生理和病理生理作用的有用探针，并为开发治疗慢性神经性和炎性疼痛的新型疗法提供了基础。

  DOI：

  10.3987/com-19-s(f)5

文献信息

• [EN] ION CHANNEL INHIBITORY COMPOUNDS, PHARMACEUTICAL FORMULATIONS AND USES<br/>[FR] COMPOSÉS INHIBITEURS DE CANAUX IONIQUES, FORMULATIONS PHARMACEUTIQUES, ET UTILISATIONS
  申请人：AFASCI INC

  公开号：WO2017083867A1

  公开（公告）日：2017-05-18

  The present invention is directed towards new chemical entities which primarily inhibit the human T-type calcium channels and differentially modulate other key ion channels to control cell excitability, and abnormal neuronal activity particularly involved in the development and maintenance of persistent or chronic pain, and / or neurological disorders. These novel compounds are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which these ion channels are involved. The invention is also directed towards pharmaceutical formulations comprising these compounds and the uses of these compounds.

  本发明主要针对新的化学实体，其主要抑制人类T型钙通道，并差异调节其他关键离子通道，以控制细胞兴奋性，以及参与持续性或慢性疼痛的发展和维持，和/或神经系统疾病的异常神经元活动。这些新颖化合物对治疗和预防这些离子通道参与的神经和精神疾病和疾病具有用处。该发明还涉及包含这些化合物的药物配方以及这些化合物的用途。
• Ion channel inhibitory compounds, pharmaceutical formulations, and uses
  申请人：AFASCI, Inc.

  公开号：US10562857B2

  公开（公告）日：2020-02-18

  The present invention is directed towards new chemical entities which primarily inhibit the human T-type calcium channels and differentially modulate other key ion channels to control cell excitability, and abnormal neuronal activity particularly involved in the development and maintenance of persistent or chronic pain, and/or neurological disorders. These novel compounds are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which these ion channels are involved. The invention is also directed towards pharmaceutical formulations comprising these compounds and the uses of these compounds.

  本发明针对的新化学实体主要抑制人类 T 型钙通道，并对其他关键离子通道进行不同程度的调节，以控制细胞兴奋性和异常神经元活动，特别是与持续或慢性疼痛和/或神经紊乱的发展和维持有关的异常神经元活动。这些新型化合物可用于治疗和预防涉及这些离子通道的神经和精神疾病。本发明还涉及包含这些化合物的药物制剂以及这些化合物的用途。
• ION CHANNEL INHIBITORY COMPOUNDS, PHARMACEUTICAL FORMULATIONS AND USES
  申请人：Afasci, Inc.

  公开号：EP3340988A1

  公开（公告）日：2018-07-04
• Ion Channel Inhibitory Compounds, Pharmaceutical Formulations, and Uses
  申请人：AFASCI, Inc.

  公开号：US20180312471A1

  公开（公告）日：2018-11-01

  The present invention is directed towards new chemical entities which primarily inhibit the human T-type calcium channels and differentially modulate other key ion channels to control cell excitability, and abnormal neuronal activity particularly involved in the development and maintenance of persistent or chronic pain, and/or neurological disorders. These novel compounds are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which these ion channels are involved. The invention is also directed towards pharmaceutical formulations comprising these compounds and the uses of these compounds.
• Synthesis of 1,3,4-Oxadiazoles as Selective T-Type Calcium Channel Inhibitors
  作者：Duy H. Hua、Xinmin Simon Xie、Man Zhang、Bende Zou、Medha J. Gunaratna、Sahani Weerasekara、Zongbo Tong、Thi D. T. Nguyen、Serkan Koldas、William S. Cao、Conrado Pascual

  DOI：10.3987/com-19-s(f)5

  日期：——

  Neuropathic pain, epilepsy, insomnia, and tremor disorder may arrive from an increase of intracellular Ca2+ concentration through a dysfunction of T-type Ca2+ channels. Thus, T-type calcium channels could be a target in drug discovery for the treatments of neuropathic pain and epilepsy. From rational drug design approach, a group of 2,5-disubstituted 1,3,4-oxadiazole molecules was synthesized and their

  神经性疼痛，癫痫，失眠和震颤症可能是由于T型Ca2 +通道功能异常导致细胞内Ca2 +浓度升高而引起的。因此，T型钙通道可能成为治疗神经性疼痛和癫痫的药物开发目标。通过合理的药物设计方法，合成了一组2,5-二取代的1,3,4-恶二唑分子，并评估了其对选择性T型通道的抑制作用。合成策略由三个反应的简短序列组成：（i）硫代氨基脲与酰氯的缩合；（ii）被1，3-二溴-5，5-二甲基乙内酰脲闭合的环；（iii）与各种酰氯偶联。5-氯-N-（5-苯基-1,3，发现4-恶二唑-2-基）噻吩-2-羧酰胺（11）选择性抑制小鼠背根神经节神经元和/或人胚肾（HEK）-293细胞中Na +和K +通道上的T型Ca2 +通道和在小鼠模型中抑制癫痫发作引起的死亡。因此，化合物11是研究T通道的生理和病理生理作用的有用探针，并为开发治疗慢性神经性和炎性疼痛的新型疗法提供了基础。