2-chloro-N-methyl-N-(4-methylthiazol-2-yl)acetamide | 50772-61-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-chloro-N-methyl-N-(4-methylthiazol-2-yl)acetamide
• 英文别名: 2-chloro-N-methyl-N-(4-methyl-1,3-thiazol-2-yl)acetamide
• CAS: 50772-61-7
• 化学式: C₇H₉ClN₂OS
• 分子量: 204.68
• InChiKey: ZARWMRBXPUCAKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  61.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-Phenylpyridine-2-thiol 、 2-chloro-N-methyl-N-(4-methylthiazol-2-yl)acetamide 在 caesium carbonate 作用下， 以 乙腈 为溶剂， 反应 18.0h， 生成 N-methyl-N-(4-methyl-1,3-thiazol-2-yl)-2-(5-phenylpyridin-2-yl)sulfanylacetamide
  参考文献：
  名称：

  Further optimization of the K-Cl cotransporter KCC2 antagonist ML077: Development of a highly selective and more potent in vitro probe

  摘要：

  Further chemical optimization of the MLSCN/MLPCN probe ML077 (KCC2 IC50 = 537 nM) proved to be challenging as the effort was characterized by steep SAR. However, a multi-dimensional iterative parallel synthesis approach proved productive. Herein we report the discovery and SAR of an improved novel antagonist (VU0463271) of the neuronal-specific potassium-chloride cotransporter 2 (KCC2), with an IC50 of 61 nM and > 100-fold selectivity versus the closely related Na-K-2Cl cotransporter 1 (NKCC1) and no activity in a larger panel of GPCRs, ion channels and transporters. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.126
• 作为产物：
  描述：

  (4-甲基-噻唑-2-基)-甲胺 、 氯乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 2-chloro-N-methyl-N-(4-methylthiazol-2-yl)acetamide
  参考文献：
  名称：

  Further optimization of the K-Cl cotransporter KCC2 antagonist ML077: Development of a highly selective and more potent in vitro probe

  摘要：

  Further chemical optimization of the MLSCN/MLPCN probe ML077 (KCC2 IC50 = 537 nM) proved to be challenging as the effort was characterized by steep SAR. However, a multi-dimensional iterative parallel synthesis approach proved productive. Herein we report the discovery and SAR of an improved novel antagonist (VU0463271) of the neuronal-specific potassium-chloride cotransporter 2 (KCC2), with an IC50 of 61 nM and > 100-fold selectivity versus the closely related Na-K-2Cl cotransporter 1 (NKCC1) and no activity in a larger panel of GPCRs, ion channels and transporters. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.126

文献信息

• [EN] COMBINATION THERAPY FOR TREATING MPS1<br/>[FR] POLYTHÉRAPIE POUR LE TRAITEMENT DE LA MPS1
  申请人：GAIN THERAPEUTICS SA

  公开号：WO2021156774A1

  公开（公告）日：2021-08-12

  The application is directed to compounds of formula (I) and their salts and solvates, wherein B, R1, R2, R3, R3', R4, R4', and R5 are as set forth in the specification, as well as to methods for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of, e.g., MPS1, optionally in combination with α-L-iduronidase or an analog or variant thereof, e.g., laronidase.

  该申请涉及公式(I)化合物及其盐和溶剂化合物，其中B、R1、R2、R3、R3'、R4、R4'和R5如规范中所述，以及其制备方法、含有相同化合物的药物组合物，以及用于治疗和/或预防MPS1等疾病的方法，可选地与α-L-异硫酸酶或其类似物或变体（例如，laronidase）结合使用。
• COMBINATION THERAPY FOR TREATING MPS1
  申请人：Gain Therapeutics SA

  公开号：EP4100015A1

  公开（公告）日：2022-12-14