methyl 5-(3,3-dimethylbut-1-ynyl)-3-(4-oxocyclohexylamino)thiophene-2-carboxylate | 1263101-15-0

• 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-(4-oxocyclohexylamino)thiophene-2-carboxylate
• 英文别名: 5-(3,3-dimethyl-but-1-ynyl)-3-(4-oxo-cyclohexylamino)-thiophene-2-carboxylic acid methyl ester；methyl 5-(3,3-dimethylbut-1-ynyl)-3-[(4-oxocyclohexyl)amino]thiophene-2-carboxylate
• CAS: 1263101-15-0
• 化学式: C₁₈H₂₃NO₃S
• 分子量: 333.452
• InChiKey: BGKRDBFFMXBMQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  83.6
• 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-(4-oxocyclohexylamino)thiophene-2-carboxylate 在 三乙基硅烷 、 iron(III) chloride 、 sodium hydride 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 、 1,2-二氯乙烷 、 mineral oil 为溶剂， 反应 3.25h， 生成 methyl 3-((3r,6r)-1-oxaspiro[2.5]octan-6-ylamino)-5-(3,3-dimethylbut-1-ynyl)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
• 作为产物：
  描述：

  methyl 3-amino-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylate 在 盐酸 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 生成 methyl 5-(3,3-dimethylbut-1-ynyl)-3-(4-oxocyclohexylamino)thiophene-2-carboxylate
  参考文献：
  名称：

  [EN] 5-ALKYNYL-THIOPHENE-2-CARBOXYLIC ACID DERIVATIVES AND THEIR USE FOR THE TREATMENT OR PREVENTION OF FLAVIVIRUS INFECTIONS
  [FR] DÉRIVÉS D'ACIDE 5-ALCYNYL-THIOPHÈNE-2-CARBOXYLIQUE ET LEUR UTILISATION POUR TRAITER OU PRÉVENIR DES INFECTIONS À FLAVIVIRUS

  摘要：

  由公式(I)代表的化合物或其药用可接受的盐，其中R1、R2和R3如本文所定义，对治疗黄病毒科病毒感染有用。

  公开号：

  WO2011068715A1

文献信息

• INHIBITORS OF FLAVIVIRIDAE VIRUSES
  申请人：Canales Eda

  公开号：US20110020278A1

  公开（公告）日：2011-01-27

  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, particularly hepatitis C infections.

  提供的是I式化合物： 及其药用可接受的盐和酯。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，特别是丙型肝炎感染，是有用的。
• [EN] 5-ALKYNYL-THIOPHENE-2-CARBOXYLIC ACID DERIVATIVES AND THEIR USE FOR THE TREATMENT OR PREVENTION OF FLAVIVIRUS INFECTIONS<br/>[FR] DÉRIVÉS D'ACIDE 5-ALCYNYL-THIOPHÈNE-2-CARBOXYLIQUE ET LEUR UTILISATION POUR TRAITER OU PRÉVENIR DES INFECTIONS À FLAVIVIRUS
  申请人：VERTEX PHARMA

  公开号：WO2011068715A1

  公开（公告）日：2011-06-09

  Compounds represented by formula (I) :or pharmaceutically acceptable salts thereof, wherein R1, R2, and R3 are as defined herein, are useful for treating flaviviridae viral infections.

  由公式(I)代表的化合物或其药用可接受的盐，其中R1、R2和R3如本文所定义，对治疗黄病毒科病毒感染有用。
• [EN] METHODS FOR PREPARATION OF THIOPHENE COMPOUNDS<br/>[FR] PROCÉDÉS DE PRÉPARATION DE COMPOSÉS DU THIOPHÈNE
  申请人：VERTEX PHARMA

  公开号：WO2013016499A1

  公开（公告）日：2013-01-31

  A method of preparing Compound (1): or a pharmaceutically acceptable salt thereof includes: a) reacting Compound (A) with 3,3- dimetylbut-l-yne in the presence of one or more palladium catalysts selected from the group consisting of Pd(PPh3)4 and Pd(PPh3)2Cl2, and one or more copper catalysts selected from the group consisting of Cul, CuBr, and CuCl, to generate Compound (B); b) treating Compound (B) with an acid to generate Compound (C): c) reducing the cyclohexanone of Compound (C) to cyclohexanol to generate Compound (D); and d) reacting Compound (D) with a base to generate Compound (1), wherein Compounds (A), (B), (C), and (D) are each as depicted herein.

  制备化合物（1）或其药学上可接受的盐的方法包括：a）在选择自Pd（PPh3）4和Pd（PPh3）2Cl2组成的一种或多种钯催化剂和选择自Cul，CuBr和CuCl组成的一种或多种铜催化剂的存在下，将化合物（A）与3,3-二甲基丁-1-炔反应，生成化合物（B）；b）用酸处理化合物（B），生成化合物（C）；c）将化合物（C）的环己酮还原为环己醇，生成化合物（D）；和d）将化合物（D）与碱反应，生成化合物（1），其中化合物（A），（B），（C）和（D）如此处所示。
• COMPOUNDS AND METHODS FOR THE TREATMENT OR PREVENTION OF FLAVIVIRIDAE VIRAL INFECTIONS
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：US20140065103A1

  公开（公告）日：2014-03-06

  A compound is selected from the structural formulae depicted in FIG. 1 or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises a compound selected from the structural formulae depicted in FIG. 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier of excipient. A method of treating a HCV infection in a subject comprises administering to the subject a therapeutically effective amount of selected from the structural formulae depicted in FIG. 1 or a pharmaceutically acceptable salt thereof. A method of inhibiting or reducing the activity of HCV polymerase in a subject or in a biological in vitro sample comprises administering to the subject or to the sample a therapeutically effective amount of selected from the structural formulae depicted in FIG. 1 or a pharmaceutically acceptable salt thereof.

  从图1所示的结构式中选择一个化合物或其药学上可接受的盐。一种制药组合物包括从图1所示的结构式中选择的化合物或其药学上可接受的盐，以及药学上可接受的载体或赋形剂。一种治疗HCV感染的方法包括向受试者施用从图1所示的结构式中选择的化合物或其药学上可接受的盐的治疗有效量。一种抑制或减少受试者或体外生物样品中HCV聚合酶活性的方法包括向受试者或样品施用从图1所示的结构式中选择的化合物或其药学上可接受的盐的治疗有效量。
• COMPOUNDS AND METHODS FOR THE TREATMENT OR PREVENTION OF FLAVIVIRUS INFECTIONS
  申请人：Chan Chun Kong Laval

  公开号：US20130136719A1

  公开（公告）日：2013-05-30

  Compounds represented by formula I: or pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , and R 3 are as defined herein, are useful for treating flaviviridae viral infections.

  公式I所代表的化合物或其药学上可接受的盐，其中R1、R2和R3的定义如本文所述，可用于治疗黄病毒科病毒感染。