methyl 5-(3,3-dimethylbut-1-ynyl)-3-(isopropylamino)thiophene-2-carboxylate | 1417718-77-4

• 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-(isopropylamino)thiophene-2-carboxylate
• 英文别名: Methyl 5-(3,3-dimethylbut-1-ynyl)-3-(isopropylamino)thiophene-2-carboxylate；methyl 5-(3,3-dimethylbut-1-ynyl)-3-(propan-2-ylamino)thiophene-2-carboxylate
• CAS: 1417718-77-4
• 化学式: C₁₅H₂₁NO₂S
• 分子量: 279.403
• InChiKey: AKSJHEAUMPHVBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  66.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 5-(3,3-dimethylbut-1-ynyl)-3-(isopropylamino)thiophene-2-carboxylate 在 吡啶 、 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 5-(3,3-dimethylbut-1-ynyl)-3-(( 1R,6R)-N-isopropyl-4,6-dimethylcyclohex-3-enecarboxamido)thiophene-2-carboxylic acid
  参考文献：
  名称：

  [EN] THIOPHEN-2-CARBOXYLIC ACID DERIVATIVES USEFUL AS INHIBITORS OF FLAVIVIRIDAE VIRUSES
  [FR] DÉRIVÉS DE L'ACIDE THIOPHÈNE-2-CARBOXYLIQUE UTILES EN TANT QU'INHIBITEURS DES VIRUS FLAVIVIRIDAE

  摘要：

  提供的是Formula I的化合物：及其药用盐和酯。所提供的化合物、组合物和方法对于治疗黄病毒科病毒感染（例如丙型肝炎感染）特别是耐药性黄病毒科病毒感染是有用的。

  公开号：

  WO2013010112A1
• 作为产物：
  描述：

  3-氨基-2-噻吩甲酸甲酯 在 bis-triphenylphosphine-palladium(II) chloride 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.17h， 生成 methyl 5-(3,3-dimethylbut-1-ynyl)-3-(isopropylamino)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

• INHIBITORS OF FLAVIVIRIDAE VIRUSES
  申请人：Watkins William J.

  公开号：US20130052161A1

  公开（公告）日：2013-02-28

  Provided are compounds of Formula I: and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of Flaviviridae virus infections (e.g. hepatitis C infections), particularly drug resistant Flaviviridae virus infections.

  提供的是式子I的化合物及其药学上可接受的盐和酯。所提供的化合物、组合物和方法对于治疗黄病毒科病毒感染（例如丙型肝炎感染）特别是耐药性黄病毒科病毒感染是有用的。
• Inhibitors of flaviviridae viruses
  申请人：Watkins William J.

  公开号：US08741946B2

  公开（公告）日：2014-06-03

  Provided are compounds of Formula I: and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of Flaviviridae virus infections (e.g. hepatitis C infections), particularly drug resistant Flaviviridae virus infections.

  提供的是I式化合物及其药物可接受的盐和酯。所提供的化合物、组合物和方法对治疗黄病毒科病毒感染（如丙型肝炎感染）特别是耐药性黄病毒科病毒感染有用。
• THIOPHEN-2-CARBOXYLIC ACID DERIVATIVES USEFUL AS INHIBITORS OF FLAVIVIRIDAE VIRUSES
  申请人：Gilead Sciences, Inc.

  公开号：EP2734515B1

  公开（公告）日：2015-11-04
• US8741946B2
  申请人：——

  公开号：US8741946B2

  公开（公告）日：2014-06-03
• Discovery of GS-9669, a Thumb Site II Non-Nucleoside Inhibitor of NS5B for the Treatment of Genotype 1 Chronic Hepatitis C Infection
  作者：Scott E. Lazerwith、Willard Lew、Jennifer Zhang、Philip Morganelli、Qi Liu、Eda Canales、Michael O. Clarke、Edward Doerffler、Daniel Byun、Michael Mertzman、Hong Ye、Lee Chong、Lianhong Xu、Todd Appleby、Xiaowu Chen、Martijn Fenaux、Ahmad Hashash、Stephanie A. Leavitt、Eric Mabery、Mike Matles、Judy W. Mwangi、Yang Tian、Yu-Jen Lee、Jingyu Zhang、Christine Zhu、Bernard P. Murray、William J. Watkins

  DOI：10.1021/jm401420j

  日期：2014.3.13

  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.