5-(3,3-dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-((1R)-4-methyl-cyclohex-3-ene carbonyl)-amino]thiophene-2-carboxylic acid methyl ester | 1384122-54-6

• 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: 5-(3,3-dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-((1R)-4-methyl-cyclohex-3-ene carbonyl)-amino]thiophene-2-carboxylic acid methyl ester
• 英文别名: 5-(3,3-dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-((1R)-4-methyl-cyclohex-3-enecarbonyl)amino]thiophene-2-carboxylic acid methyl ester；methyl 5-(3,3-dimethylbut-1-ynyl)-3-((1R)-4-methyl-N-(1,4-dioxaspiro[4.5]decan-8-yl)cyclohex-3-enecarboxamido)thiophene-2-carboxylate；5-(3,3-Dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-((1R)-4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester；methyl 5-(3,3-dimethylbut-1-ynyl)-3-[1,4-dioxaspiro[4.5]decan-8-yl-[(1R)-4-methylcyclohex-3-ene-1-carbonyl]amino]thiophene-2-carboxylate
• CAS: 1384122-54-6
• 化学式: C₂₈H₃₇NO₅S
• 分子量: 499.671
• InChiKey: WRMCRYXMORSWSL-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  93.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(3,3-dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-((1R)-4-methyl-cyclohex-3-ene carbonyl)-amino]thiophene-2-carboxylic acid methyl ester 在 盐酸 、 sodium hydride 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 、 mineral oil 为溶剂， 反应 19.58h， 生成 5-(3,3-dimethylbut-1-yn-1-yl)-3-((R)-4-methyl-N-((3S,6S)-1-oxaspiro[2.5]octan-6-yl)cyclohex-3-enecarboxamido)thiophene-2-carboxylic acid
  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：

  (R)-((S)-4,4-dimethyl-2-oxotetrahydrofuran-3-yl) 4-methylcyclohex-3-ene carboxylate 在 potassium phosphate 、 草酰氯 、 水 、 N,N-二甲基甲酰胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 19.0h， 生成 5-(3,3-dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-((1R)-4-methyl-cyclohex-3-ene carbonyl)-amino]thiophene-2-carboxylic acid methyl ester
  参考文献：
  名称：

  METHODS FOR TREATING HCV

  摘要：

  这项发明涉及治疗丙型肝炎病毒感染的治疗分子组合。本发明涉及方法、用途、给药方案和组合物。

  公开号：

  US20130273005A1

文献信息

• [EN] COMBINATIONS FOR TREATING HCV<br/>[FR] COMBINATIONS POUR TRAITER LE VHC
  申请人：GILEAD SCIENCES INC

  公开号：WO2012087596A1

  公开（公告）日：2012-06-28

  This invention relates to combinations of therapeutic molecules useful for treating hepatitis C virus infection. The present invention relates to methods, uses, dosing regimens, and compositions.

  本发明涉及治疗丙型肝炎病毒感染的治疗分子组合。本发明涉及方法、用途、剂量方案和组合物。
• INHIBITORS OF FLAVIVIRIDAE VIRUSES
  申请人：Canales Eda

  公开号：US20110178129A1

  公开（公告）日：2011-07-21

  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.

  提供的是式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热病毒感染，尤其是丙型肝炎感染非常有用。
• Methods for treating HCV
  申请人：Gilead Pharmasset LLC

  公开号：US09393256B2

  公开（公告）日：2016-07-19

  This invention relates to combinations of therapeutic molecules useful for treating hepatitis C virus infection. The present invention relates to methods, uses, dosing regimens, and compositions.

  本发明涉及治疗丙型肝炎病毒感染的治疗分子组合物。本发明涉及方法、用途、剂量方案和组合物。
• [EN] METHODS FOR TREATING HCV<br/>[FR] PROCÉDÉS PERMETTANT DE TRAITER LE VIRUS DE L'HÉPATITE C (HCV)
  申请人：GILEAD SCIENCES INC

  公开号：WO2013040492A3

  公开（公告）日：2013-07-25
• COMBINATIONS FOR TREATING HCV
  申请人：Gilead Sciences, Inc.

  公开号：EP2654900A1

  公开（公告）日：2013-10-30