(2S)-2-tert-butoxy-2-[4-(4-chlorophenyl)-2,5-dimethyl-6-(phenylcarbamoyl)-3-pyridyl]acetic acid | 1256250-77-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (2S)-2-tert-butoxy-2-[4-(4-chlorophenyl)-2,5-dimethyl-6-(phenylcarbamoyl)-3-pyridyl]acetic acid
• 英文别名: (2S)-2-[4-(4-chlorophenyl)-2,5-dimethyl-6-(phenylcarbamoyl)pyridin-3-yl]-2-[(2-methylpropan-2-yl)oxy]acetic acid
• CAS: 1256250-77-7
• 化学式: C₂₆H₂₇ClN₂O₄
• 分子量: 466.964
• InChiKey: WZRDSAYMJYUOQO-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  88.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl 4-chloro-5-[(1S)-2-methoxy-1-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-3,6-dimethylpyridine-2-carboxylate 在 二(三叔丁基膦)钯 、 水 、 potassium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2S)-2-tert-butoxy-2-[4-(4-chlorophenyl)-2,5-dimethyl-6-(phenylcarbamoyl)-3-pyridyl]acetic acid
  参考文献：
  名称：

  Aligning Potency and Pharmacokinetic Properties for Pyridine-Based NCINIs

  摘要：

  Optimization of pyridine-based noncatalytic site integrase inhibitors (NCINIs) based on compound 2 has led to the discovery of molecules capable of inhibiting virus harboring N124 variants of HIV integrase (IN) while maintaining minimal contribution of enterohepatic recirculation to clearance in rat. Structure activity relationships at the C6 position established chemical space where the extent of enterohepatic recirculation in the rat is minimized. Desymmetrization of the C4 substituent allowed for potency optimization against virus having the N124 variant of integrase. Combination of these lessons led to the discovery of compound 20, having balanced serum-shifted antiviral potency and minimized excretion in to the biliary tract in rat, potentially representing a clinically viable starting point for a new treatment option for individuals infected with HIV.

  DOI：

  10.1021/acsmedchemlett.6b00194