N¹-(4-chlorophenyl)-N²-((5-(hydroxymethyl)-4-methylthiazol-2-yl)(piperidin-2-yl)methyl)oxalamide hydrochloride | 1375736-62-1

• 英文名称: N¹-(4-chlorophenyl)-N²-((5-(hydroxymethyl)-4-methylthiazol-2-yl)(piperidin-2-yl)methyl)oxalamide hydrochloride
• 英文别名: N-(4-chlorophenyl)-N'-[[5-(hydroxymethyl)-4-methyl-1,3-thiazol-2-yl]-piperidin-2-ylmethyl]oxamide;hydrochloride
• CAS: 1375736-62-1
• 化学式: C₁₉H₂₃ClN₄O₃S*ClH
• 分子量: 459.397
• InChiKey: WKUKSZHLVLLMFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.96
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  132
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-(4-氯苯基)-2-氧代甘氨酸乙酯 在 水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 N¹-(4-chlorophenyl)-N²-((5-(hydroxymethyl)-4-methylthiazol-2-yl)(piperidin-2-yl)methyl)oxalamide hydrochloride
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Activity of Entry Inhibitors That Target the CD4-Binding Site of HIV-1

  摘要：

  The CD4 binding site on HIV-1 gp120 has been validated as a drug target to prevent HIV-1 entry to cells. Previously, we identified two small molecule inhibitors consisting of a 2,2,6,6-tetramethylpiperidine ring linked by an oxalamide to a p-halide-substituted phenyl group, which target this site, specifically, a cavity termed "Phe43 cavity". Here we use synthetic chemistry, functional assessment, and structure-based analysis to explore variants of each region of these inhibitors for improved antiviral properties. Alterations of the phenyl group and of the oxalamide linker indicated that these regions were close to optimal in the original lead compounds. Design of a series of compounds, where the tetramethylpiperidine ring was replaced with new scaffolds, led to improved antiviral activity. These new scaffolds provide insight into the surface chemistry at the entrance of the cavity and offer additional opportunities by which to optimize further these potential-next-generation therapeutics and microbicides against HIV-1.

  DOI：

  10.1021/jm3002247

文献信息

• HIV INHIBITORS
  申请人：New york Blood Center, Inc.

  公开号：US20140377219A1

  公开（公告）日：2014-12-25

  Chemical compounds that inhibit retroviruses are presented herein. More particularly, this disclosure provides small molecule compounds that inhibit infection with, or treat infection caused by, human immunodeficiency viruses.

  本文介绍了能够抑制逆转录病毒的化合物。更具体地，本文提供了能够抑制人类免疫缺陷病毒感染或治疗由此引起的感染的小分子化合物。
• US9309237B2
  申请人：——

  公开号：US9309237B2

  公开（公告）日：2016-04-12