2-{[(2,6-dichlorophenyl)methyl]sulfanyl}-5-phenyl-1,3,4-thiadiazole | 448947-83-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-{[(2,6-dichlorophenyl)methyl]sulfanyl}-5-phenyl-1,3,4-thiadiazole
• 英文别名: 2-[(2,6-dichlorophenyl)methylthio]-5-phenyl-1,3,4-thiadiazole；2-[(2,6-Dichlorophenyl)methylsulfanyl]-5-phenyl-1,3,4-thiadiazole
• CAS: 448947-83-9
• 化学式: C₁₅H₁₀Cl₂N₂S₂
• 分子量: 353.296
• InChiKey: GIODCHISYDOXEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  79.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,6-二氯氯苄 、 5-苯基-1,3,4-噻二唑-2-硫醇 在 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以58%的产率得到2-{[(2,6-dichlorophenyl)methyl]sulfanyl}-5-phenyl-1,3,4-thiadiazole
  参考文献：
  名称：

  Yoda1 analogue (Dooku1) which antagonizes Yoda1-evoked activation of Piezo1 and aortic relaxation

  摘要：

  Background and PurposeThe mechanosensitive Piezo1 channel has important roles in vascular physiology and disease. Yoda1 is a small‐molecule agonist, but the pharmacology of these channels is otherwise limited.Experimental ApproachYoda1 analogues were generated by synthetic chemistry. Intracellular Ca2+ and Tl+ measurements were made in HEK 293 or CHO cell lines overexpressing channel subunits and in HUVECs, which natively express Piezo1. Isometric tension recordings were made from rings of mouse thoracic aorta.Key ResultsModification of the pyrazine ring of Yoda1 yielded an analogue, which lacked agonist activity but reversibly antagonized Yoda1. The analogue is referred to as Dooku1. Dooku1 inhibited 2 μM Yoda1‐induced Ca2+‐entry with IC50s of 1.3 μM (HEK 293 cells) and 1.5 μM (HUVECs) yet failed to inhibit constitutive Piezo1 channel activity. It had no effect on endogenous ATP‐evoked Ca2+ elevation or store‐operated Ca2+ entry in HEK 293 cells or Ca2+ entry through TRPV4 or TRPC4 channels overexpressed in CHO and HEK 293 cells. Yoda1 caused dose‐dependent relaxation of aortic rings, which was mediated by an endothelium‐ and NO‐dependent mechanism and which was antagonized by Dooku1 and analogues of Dooku1.Conclusion and ImplicationsChemical antagonism of Yoda1‐evoked Piezo1 channel activity is possible, and the existence of a specific chemical interaction site is suggested with distinct binding and efficacy domains.

  DOI：

  10.1111/bph.14188

文献信息

• Heterocyclic inhibitors of glycine transporter 2
  申请人：——

  公开号：US20030073726A1

  公开（公告）日：2003-04-17

  Compounds, compositions, and methods for inhibiting the glycine transporter 2 and for inhibiting glycine transporter mediated neuronal activity. These compounds are particularly useful for treating diseases of the nerve and muscle, including psychoses, pain, epilepsy, neurodegenerative diseases, stroke, head trauma, multiple sclerosis and the like, and of muscle disorders, including diseases or conditions associated with increased muscle contraction, such as spasticity and myoclonus. In addition, the compounds may be used to discover other agents with improved activity in assays in which the compounds of the invention are active.

  用于抑制甘氨酸转运蛋白2和抑制甘氨酸转运蛋白介导的神经活动的化合物、组合物和方法。这些化合物特别适用于治疗神经和肌肉疾病，包括精神病、疼痛、癫痫、神经退行性疾病、中风、头部创伤、多发性硬化等，以及肌肉疾病，包括与肌肉过度收缩相关的疾病或症状，如痉挛和肌阵挛。此外，这些化合物可用于发现在这些化合物具有活性的检测中具有改进活性的其他药物。
• HETEROCYCLIC INHIBITORS OF GLYCINE TRANSPORTER 2
  申请人：TELIK, INC.

  公开号：EP1357913A1

  公开（公告）日：2003-11-05
• US6894054B2
  申请人：——

  公开号：US6894054B2

  公开（公告）日：2005-05-17
• [EN] HETEROCYCLIC INHIBITORS OF GLYCINE TRANSPORTER 2<br/>[FR] INHIBITEURS HETEROCYCLIQUES DU TRANSPORTEUR DE GLYCINE 2
  申请人：TELIK INC

  公开号：WO2002064135A1

  公开（公告）日：2002-08-22

  The invention provides compounds, compositions and methods for inhibiting the glycine transporter (2) and for affecting glycine transporter mediated neuronal activity. Useful compounds comprise compounds of Formula I : wherein n is (0, 1, 2 or 3) and R is independently halogen, hydroxy, lower alkyl optionally substituted with halogen or lower alkoxy optionally substituted with halogen; X is O, S or N-R' (wherein R's is lower alkyl, aryl, heteroaryl, aryl-lower alkylene or heteroaryl-lower alkylene); Q may be absent or present, and when present, it is represented by the formula : in which n, R and X are as defined above; when Q is present, W is a lower alkylene and when Q is absent, W is optionally substituted lower alkyl, optionally substituted aryl, optionally substituted heteroaryl (optionally substituted aryl)-X-CH2-or (optionally substituted heteroaryl)-X-CH2-in which X is as defined above; or a pharmaceutically acceptable salt thereof. These compounds are particularly useful for treating diseases of the nerve and muscle, including psychoses, pain, epilepsy, neurodegenerative diseases, stroke, head trauma, multiple sclerosis and the like, and of muscle disorders, including diseases or conditions associated with increased muscle contraction, such as spasticity and myoclonus. In addition, the compounds may be used to discover other agents with improved activity in assays in which the compounds of the invention are active.
• Yoda1 analogue (Dooku1) which antagonizes Yoda1-evoked activation of Piezo1 and aortic relaxation
  作者：Elizabeth L Evans、Kevin Cuthbertson、Naima Endesh、Baptiste Rode、Nicola M Blythe、Adam J Hyman、Sally J Hall、Hannah J Gaunt、Melanie J Ludlow、Richard Foster、David J Beech

  DOI：10.1111/bph.14188

  日期：2018.5

  Background and PurposeThe mechanosensitive Piezo1 channel has important roles in vascular physiology and disease. Yoda1 is a small‐molecule agonist, but the pharmacology of these channels is otherwise limited.Experimental ApproachYoda1 analogues were generated by synthetic chemistry. Intracellular Ca2+ and Tl+ measurements were made in HEK 293 or CHO cell lines overexpressing channel subunits and in HUVECs, which natively express Piezo1. Isometric tension recordings were made from rings of mouse thoracic aorta.Key ResultsModification of the pyrazine ring of Yoda1 yielded an analogue, which lacked agonist activity but reversibly antagonized Yoda1. The analogue is referred to as Dooku1. Dooku1 inhibited 2 μM Yoda1‐induced Ca2+‐entry with IC50s of 1.3 μM (HEK 293 cells) and 1.5 μM (HUVECs) yet failed to inhibit constitutive Piezo1 channel activity. It had no effect on endogenous ATP‐evoked Ca2+ elevation or store‐operated Ca2+ entry in HEK 293 cells or Ca2+ entry through TRPV4 or TRPC4 channels overexpressed in CHO and HEK 293 cells. Yoda1 caused dose‐dependent relaxation of aortic rings, which was mediated by an endothelium‐ and NO‐dependent mechanism and which was antagonized by Dooku1 and analogues of Dooku1.Conclusion and ImplicationsChemical antagonism of Yoda1‐evoked Piezo1 channel activity is possible, and the existence of a specific chemical interaction site is suggested with distinct binding and efficacy domains.