methyl 5-(3,3-dimethylbut-1-ynyl)-3-(1-methylpiperidin-4-ylamino)thiophene-2-carboxylate | 1485469-53-1

• 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: methyl 5-(3,3-dimethylbut-1-ynyl)-3-(1-methylpiperidin-4-ylamino)thiophene-2-carboxylate
• 英文别名: Methyl 5-(3,3-dimethylbut-1-ynyl)-3-[(1-methylpiperidin-4-yl)amino]thiophene-2-carboxylate
• CAS: 1485469-53-1
• 化学式: C₁₈H₂₆N₂O₂S
• 分子量: 334.483
• InChiKey: WMRRBFPMINWBLI-UHFFFAOYSA-N

物化性质

• 沸点：
  470.3±45.0 °C(predicted)
• 密度：
  1.14±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  69.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 5-(3,3-dimethylbut-1-ynyl)-3-(1-methylpiperidin-4-ylamino)thiophene-2-carboxylate 在 1-氯乙基氯甲酸酯 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 5-(3,3-dimethyl-but-1-ynyl)-3-[(4-methyl-cyclohexanecarbonyl)-piperidin-4-ylamino]-thiophene-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Discovery of GS-9669, a Thumb Site II Non-Nucleoside Inhibitor of NS5B for the Treatment of Genotype 1 Chronic Hepatitis C Infection

  摘要：

  Investigation of thiophene-2-carboxylic acid HCV NS5B site II inhibitors, guided by measurement of cell culture medium binding, revealed the structure activity relationships for intrinsic cellular potency. The pharmacokinetic profile was enhanced through incorporation of heterocyclic ethers on the N-alkyl substituent. Hydroxyl groups were incorporated to modulate protein binding. Intrinsic potency was further improved through enantiospecific introduction of an olefin in the N-acyl motif, resulting in the discovery of the phase 2 clinical candidate GS-9669. The unexpected activity of this compound against the clinically relevant NS5B M423T mutant, relative to the wild type, was shown to arise from both the N-alkyl substituent and the N-acyl group.

  DOI：

  10.1021/jm401420j
• 作为产物：
  描述：

  5-(3,3-dimethylbut-1-ynyl)-3-iodothiophene-2-carboxylic acid 在 吡啶 、 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 21.17h， 生成 methyl 5-(3,3-dimethylbut-1-ynyl)-3-(1-methylpiperidin-4-ylamino)thiophene-2-carboxylate
  参考文献：
  名称：

  Discovery of GS-9669, a Thumb Site II Non-Nucleoside Inhibitor of NS5B for the Treatment of Genotype 1 Chronic Hepatitis C Infection

  摘要：

  Investigation of thiophene-2-carboxylic acid HCV NS5B site II inhibitors, guided by measurement of cell culture medium binding, revealed the structure activity relationships for intrinsic cellular potency. The pharmacokinetic profile was enhanced through incorporation of heterocyclic ethers on the N-alkyl substituent. Hydroxyl groups were incorporated to modulate protein binding. Intrinsic potency was further improved through enantiospecific introduction of an olefin in the N-acyl motif, resulting in the discovery of the phase 2 clinical candidate GS-9669. The unexpected activity of this compound against the clinically relevant NS5B M423T mutant, relative to the wild type, was shown to arise from both the N-alkyl substituent and the N-acyl group.

  DOI：

  10.1021/jm401420j

文献信息

• Thiophene analogues for the treatment or prevention of flavivirus infections
  申请人：Chan Chun Kong Laval

  公开号：US20080299080A1

  公开（公告）日：2008-12-04

  Compounds represented by formula I: or pharmaceutically acceptable salts and solvates thereof, wherein R 1 , X, Y, and Z are as defined herein, are useful for treating flaviviridae viral infections.

  式I所代表的化合物，或其药用可接受的盐和溶剂化物，其中R1、X、Y和Z的定义如本文所述，可用于治疗黄病毒科病毒感染。
• THIOPHENE ANALOGUES FOR THE TREATMENT OR PREVENTION OF FLAVIVIRUS INFECTIONS
  申请人：Chan Chun Kong Laval

  公开号：US20120059170A1

  公开（公告）日：2012-03-08

  Compounds represented by formula I: or pharmaceutically acceptable salts and solvates thereof, wherein R 1 , X, Y, and Z are as defined herein, are useful for treating flaviviridae viral infections.

  式I所代表的化合物或其药学上可接受的盐和溶剂合物，其中R1、X、Y和Z的定义如本文所述，可用于治疗黄病毒科病毒感染。
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