(2S)-2-[6-benzamido-4-(4-chlorophenyl)-2,5-dimethyl-3-pyridyl]-2-tert-butoxy-acetic acid | 1256250-98-2

• 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-[6-benzamido-4-(4-chlorophenyl)-2,5-dimethyl-3-pyridyl]-2-tert-butoxy-acetic acid
• 英文别名: (2S)-2-[6-benzamido-4-(4-chlorophenyl)-2,5-dimethylpyridin-3-yl]-2-[(2-methylpropan-2-yl)oxy]acetic acid
• CAS: 1256250-98-2
• 化学式: C₂₆H₂₇ClN₂O₄
• 分子量: 466.964
• InChiKey: JDXNLRPXJONIMS-QFIPXVFZSA-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 (2S)-2-(4,6-dichloro-2,5-dimethylpyridin-3-yl)-2-[(2-methylpropan-2-yl)oxy]acetate 在 二(三叔丁基膦)钯 、 dicyclohexyl(3-dicyclohexylphosphaniumylpropyl)phosphonium ditetrafluoroborate 、 叠氮磷酸二苯酯 、 水 、 palladium diacetate 、 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 、 甲苯 为溶剂， 生成 (2S)-2-[6-benzamido-4-(4-chlorophenyl)-2,5-dimethyl-3-pyridyl]-2-tert-butoxy-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

文献信息

• [EN] INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION<br/>[FR] INHIBITEURS DE LA REPLICATION DU VIRUS DE L'IMMUNODEFICIENCE HUMAINE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2010130034A1

  公开（公告）日：2010-11-18

  Compounds of formula I wherein a, R1, R2, R3, R4, R5 and R6 are defined herein, are useful as inhibitors of HIV replication.

  式I中的化合物，其中a、R1、R2、R3、R4、R5和R6如本文所定义，可用作HIV复制抑制剂。
• INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
  申请人：BOEHRINGER INGELHEIM INTERNATIONAL GMBH

  公开号：EP2429993B1

  公开（公告）日：2015-01-21
• US8338441B2
  申请人：——

  公开号：US8338441B2

  公开（公告）日：2012-12-25
• US8841331B2
  申请人：——

  公开号：US8841331B2

  公开（公告）日：2014-09-23
• Aligning Potency and Pharmacokinetic Properties for Pyridine-Based NCINIs
  作者：Lee D. Fader、Murray Bailey、Eric Beaulieu、François Bilodeau、Pierre Bonneau、Yves Bousquet、Rebekah J. Carson、Catherine Chabot、René Coulombe、Jianmin Duan、Craig Fenwick、Michel Garneau、Ted Halmos、Araz Jakalian、Clint James、Stephen H. Kawai、Serge Landry、Steven R. LaPlante、Stephen W. Mason、Sebastien Morin、Nathalie Rioux、Bruno Simoneau、Simon Surprenant、Bounkham Thavonekham、Carl Thibeault、Thao Trinh、Youla Tsantrizos、Jennifer Tsoung、Christiane Yoakim、Dominik Wernic

  DOI：10.1021/acsmedchemlett.6b00194

  日期：2016.8.11

  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.