methyl 3-cyano-3-(3,4-dichlorophenyl)-6-(tetrahydro-2H-pyran-2-yloxy)hexanoate | 716327-26-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 3-cyano-3-(3,4-dichlorophenyl)-6-(tetrahydro-2H-pyran-2-yloxy)hexanoate
• 英文别名: Methyl 3-cyano-3-(3,4-dichlorophenyl)-6-(oxan-2-yloxy)hexanoate
• CAS: 716327-26-3
• 化学式: C₁₉H₂₃Cl₂NO₄
• 分子量: 400.302
• InChiKey: YZYYXSXWACVGCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  68.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-cyano-3-(3,4-dichlorophenyl)-6-(tetrahydro-2H-pyran-2-yloxy)hexanoate 在 ammonium hydroxide 、 Ra-Ni 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、275.8 kPa 条件下， 生成 4-(3,4-dichloro-phenyl)-4-[3-(tetrahydro-pyran-2-yl-oxy)-propyl]-pyrrolidine
  参考文献：
  名称：

  Discovery of Bioavailable 4,4-Disubstituted Piperidines as Potent Ligands of the Chemokine Receptor 5 and Inhibitors of the Human Immunodeficiency Virus-1

  摘要：

  We describe robust chemical approaches toward putative CCR5 scaffolds designed in our laboratories. Evaluation of analogues in the (125)I-[MIP-1 beta] binding and Ba-L-HOS antiviral assays resulted in the discovery of 64 and 68 in the 4,4-disubstitited piperidine class H, both potent CCR5 ligands (pIC(50) = 8.30 and 9.00, respectively) and HIV-1 inhibitors (pIC(50) = 7.80 and 7.84, respectively, in Ba-L-HOS assay). In addition, 64 and 68 were bioavailable in rodents, establishing them as lead molecules for further optimization toward CCR5 clinical candidates.

  DOI：

  10.1021/jm800598a
• 作为产物：
  描述：

  2-(3-溴丙氧基)四氢-2H-吡喃 、 methyl 3-cyano-3-(3,4-dichlorophenyl)propanoate 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 4.17h， 以60%的产率得到methyl 3-cyano-3-(3,4-dichlorophenyl)-6-(tetrahydro-2H-pyran-2-yloxy)hexanoate
  参考文献：
  名称：

  [EN] PYRROLIDINE AND AZETIDINE COMPOUNDS AS CCR5 ANTAGONISTS
  [FR] COMPOSES DE PYRROLIDINE ET D'AZETIDINE SERVANT D'ANTAGONISTES DE CCR5

  摘要：

  本发明涉及式(I)的化合物，或其药学上可接受的衍生物，用于治疗与CCR5相关的疾病和疾病，例如，用于抑制HIV复制，预防或治疗HIV感染，并用于治疗由此导致的获得性免疫缺陷综合症（AIDS）。

  公开号：

  WO2004055016A1

文献信息

• [EN] PYRROLIDINE AND AZETIDINE COMPOUNDS AS CCR5 ANTAGONISTS<br/>[FR] COMPOSES DE PYRROLIDINE ET D'AZETIDINE SERVANT D'ANTAGONISTES DE CCR5
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004055016A1

  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 of CCR5-related diseases and disorders, for example, useful 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).

  本发明涉及式(I)的化合物，或其药学上可接受的衍生物，用于治疗与CCR5相关的疾病和疾病，例如，用于抑制HIV复制，预防或治疗HIV感染，并用于治疗由此导致的获得性免疫缺陷综合症（AIDS）。
• PYRROLIDINE AND AZETIDINE COMPOUNDS AS CCR5 ANTAGONISTS
  申请人：SmithKline Beecham Corporation

  公开号：EP1569933B1

  公开（公告）日：2008-07-23
• US7271172B2
  申请人：——

  公开号：US7271172B2

  公开（公告）日：2007-09-18
• Discovery of Bioavailable 4,4-Disubstituted Piperidines as Potent Ligands of the Chemokine Receptor 5 and Inhibitors of the Human Immunodeficiency Virus-1
  作者：Wieslaw M. Kazmierski、Christopher Aquino、Brian A. Chauder、Felix Deanda、Robert Ferris、Deborah K. Jones-Hertzog、Terrence Kenakin、Cecilia S. Koble、Christian Watson、Pat Wheelan、Hanbiao Yang、Michael Youngman

  DOI：10.1021/jm800598a

  日期：2008.10.23

  We describe robust chemical approaches toward putative CCR5 scaffolds designed in our laboratories. Evaluation of analogues in the (125)I-[MIP-1 beta] binding and Ba-L-HOS antiviral assays resulted in the discovery of 64 and 68 in the 4,4-disubstitited piperidine class H, both potent CCR5 ligands (pIC(50) = 8.30 and 9.00, respectively) and HIV-1 inhibitors (pIC(50) = 7.80 and 7.84, respectively, in Ba-L-HOS assay). In addition, 64 and 68 were bioavailable in rodents, establishing them as lead molecules for further optimization toward CCR5 clinical candidates.