2-Cyano-2-[1-[(2-methylpropan-2-yl)oxycarbonyl]-4-(3-methylsulfanylphenyl)piperidin-4-yl]acetic acid | 716360-11-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-Cyano-2-[1-[(2-methylpropan-2-yl)oxycarbonyl]-4-(3-methylsulfanylphenyl)piperidin-4-yl]acetic acid
• CAS: 716360-11-1
• 化学式: C₂₀H₂₆N₂O₄S
• 分子量: 390.503
• InChiKey: NOEFXMFHVMMISH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-Cyano-2-[1-[(2-methylpropan-2-yl)oxycarbonyl]-4-(3-methylsulfanylphenyl)piperidin-4-yl]acetic acid 在 copper(I) oxide 、 二异丁基氢化铝 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 生成 t-butyl 4-[3-(methylthio)phenyl]-4-(2-oxoethyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Novel 4,4-Disubstituted Piperidine-Based C–C Chemokine Receptor-5 Inhibitors with High Potency against Human Immunodeficiency Virus-1 and an Improved human Ether-a-go-go Related Gene (hERG) Profile

  摘要：

  We recently described (J. Med. Chem. 2008, 51, 6538-6546) a novel class of CCR5 antagonists with strong anti-HIV potency. Herein, we detail SAR converting leads 1 and 2 to druglike molecules. The pivotal structural motif enabling this transition was the secondary sulfonamide substituent. Further fine-tuning of the substituent pattern in the sulfonamide paved the way to enhancing potency and bioavailability and minimizing hERG inhibition, resulting in discovery of clinical compound 122 (GSK163929).

  DOI：

  10.1021/jm200279v
• 作为产物：
  描述：

  4-(1-氰基-2-乙氧基-2-氧代亚乙基)-1-哌啶羧酸-1,1-二甲基乙酯 在 copper(l) iodide 、 水 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 2-Cyano-2-[1-[(2-methylpropan-2-yl)oxycarbonyl]-4-(3-methylsulfanylphenyl)piperidin-4-yl]acetic acid
  参考文献：
  名称：

  Novel 4,4-Disubstituted Piperidine-Based C–C Chemokine Receptor-5 Inhibitors with High Potency against Human Immunodeficiency Virus-1 and an Improved human Ether-a-go-go Related Gene (hERG) Profile

  摘要：

  We recently described (J. Med. Chem. 2008, 51, 6538-6546) a novel class of CCR5 antagonists with strong anti-HIV potency. Herein, we detail SAR converting leads 1 and 2 to druglike molecules. The pivotal structural motif enabling this transition was the secondary sulfonamide substituent. Further fine-tuning of the substituent pattern in the sulfonamide paved the way to enhancing potency and bioavailability and minimizing hERG inhibition, resulting in discovery of clinical compound 122 (GSK163929).

  DOI：

  10.1021/jm200279v

文献信息

• Ccr5 antagonists as therapeutic agents
  申请人：Kazmierski Mieczyslaw Wieslaw

  公开号：US20060229336A1

  公开（公告）日：2006-10-12

  The present invention relates to compounds of formula (I) or a pharmaceutically acceptable derivatives thereof, useful in the treatment of prophylazis of CCR5-related diseases and disorders, for example, in the inhibition of HIV replication, the prevention or treatment of HIV infection, and in the treatment of the resulting acquired immune deficiency syndrome (AIDS).

  本发明涉及式(I)化合物或其药学上可接受的衍生物，用于预防CCR5相关疾病和障碍的治疗，例如，抑制HIV复制，预防或治疗HIV感染，以及治疗由此产生的获得性免疫缺陷综合症（AIDS）。
• PIPERIDINE DERIVATIVES AS CCR5 ANTAGONISTS
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1569646A2

  公开（公告）日：2005-09-07
• US7645771B2
  申请人：——

  公开号：US7645771B2

  公开（公告）日：2010-01-12
• [EN] CCR5 ANTAGONISTS AS THERAPEUTIC AGENTS<br/>[FR] ANTAGONISTES DE CCR5 UTILES COMME AGENTS THERAPEUTIQUES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004054974A2

  公开（公告）日：2004-07-01

  The present invention relates to compounds of formula (I) or pharmaceutically acceptable derivatives thereof, useful in the treatment or prophylaxis of CCR5-related diseases and disorders, for example, in the inhibition of HIV replication, the prevention or treatment of an HIV infection, and in the treatment of the resulting acquired immune deficiency syndrome (AIDS).