(S)-2-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-((methoxycarbonyl)amino)acetic acid | 1352932-65-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-((methoxycarbonyl)amino)acetic acid
• 英文别名: (2S)-2-[(4S)-2,2-dimethyloxan-4-yl]-2-(methoxycarbonylamino)acetic acid
• CAS: 1352932-65-0
• 化学式: C₁₁H₁₉NO₅
• 分子量: 245.276
• InChiKey: ARVYNIUWNHGVMK-YUMQZZPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-((methoxycarbonyl)amino)acetic acid 、 methyl ((S)-1-((S)-2-(4-((S)-6-(5-cyclopropylthiophen-2-yl)-1-fluoro-10-(2-((S)pyrrolidin-2-yl)-1H-imidazol-5-yl)-6H-benzo-[5,6][1,3]oxazino[3,4-a]indol-3-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate hydrochloride 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 methyl ((S)-2-((S)-2-(5-((S)-6-(5-cyclopropylthiophen-2-yl)-1-fluoro-3-(2-((S)-1-((methoxycarbonyl)-L-valyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-6H-benzo[5,6][1,3]oxazino[3,4-a]indol-10-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-1-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-oxoethyl)carbamate
  参考文献：
  名称：

  Discovery of MK-6169, a Potent Pan-Genotype Hepatitis C Virus NS5A Inhibitor with Optimized Activity against Common Resistance-Associated Substitutions

  摘要：

  We describe the discovery of MK-6169, a potent and pan-genotype hepatitis C virus NS5A inhibitor with optimized activity against common resistance-associated substitutions. SAR studies around the combination of changes to both the valine and aminal carbon region of elbasvir led to the discovery of a series of compounds with substantially improved potency against common resistance-associated substitutions in the major genotypes, as well as good pharmacokinetics in both rat and dog. Through further optimization of key leads from this effort, MK-6169 (21) was discovered as a preclinical candidate for further development.

  DOI：

  10.1021/acs.jmedchem.7b01927
• 作为产物：
  描述：

  四氢-2 2-二甲基-4H-吡喃-4-酮 在 palladium 10% on activated carbon 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 25.0 ℃ 、241.32 kPa 条件下， 反应 81.0h， 生成 (S)-2-((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-((methoxycarbonyl)amino)acetic acid
  参考文献：
  名称：

  Discovery of MK-6169, a Potent Pan-Genotype Hepatitis C Virus NS5A Inhibitor with Optimized Activity against Common Resistance-Associated Substitutions

  摘要：

  We describe the discovery of MK-6169, a potent and pan-genotype hepatitis C virus NS5A inhibitor with optimized activity against common resistance-associated substitutions. SAR studies around the combination of changes to both the valine and aminal carbon region of elbasvir led to the discovery of a series of compounds with substantially improved potency against common resistance-associated substitutions in the major genotypes, as well as good pharmacokinetics in both rat and dog. Through further optimization of key leads from this effort, MK-6169 (21) was discovered as a preclinical candidate for further development.

  DOI：

  10.1021/acs.jmedchem.7b01927