N-[[4-(3-chlorophenyl)-1,3-thiazol-2-yl]methyl]-4-(1,8-naphthyridin-2-yl)butanamide | 1314796-34-3

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: N-[[4-(3-chlorophenyl)-1,3-thiazol-2-yl]methyl]-4-(1,8-naphthyridin-2-yl)butanamide
• CAS: 1314796-34-3
• 化学式: C₂₂H₁₉ClN₄OS
• 分子量: 422.938
• InChiKey: AZBVGGJDBOFQAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  96
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-乙酰基丁酸乙酯 在 lithium hydroxide monohydrate 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 L-脯氨酸 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.0h， 生成 N-[[4-(3-chlorophenyl)-1,3-thiazol-2-yl]methyl]-4-(1,8-naphthyridin-2-yl)butanamide
  参考文献：
  名称：

  Discovery of a potent and selective small molecule hGPR91 antagonist

  摘要：

  GPR91, a 7TM G-Protein-Coupled Receptor, has been recently deorphanized with succinic acid as its endogenous ligand. Current literature indicates that GPR91 plays role in various pathophysiology including renal hypertension, autoimmune disease and retinal angiogenesis. Starting from a small molecule high-throughput screening hit 1 (hGPR91 IC(50): 0.8 mu M)-originally synthesized in Merck for Bradykinin B(1) Receptor (BK(1)R) program, systematic structure-activity relationship study led us to discover potent and selective hGPR91 antagonists e.g. 2c, 4c, and 5g (IC(50): 7-35 nM; >1000 fold selective against hGPR99, a closest related GPCR; > 100 fold selective in Drug Matrix screening). This initial work also led to identification of two structurally distinct and orally bio-available lead compounds: 5g (%F: 26) and 7e (IC(50): 180 nM; > 100 fold selective against hGPR99; %F: 87). A rat pharmacodynamic assay was developed to characterize the antagonists in vivo using succinate induced increase in blood pressure. Using two representative antagonists, 2c and 4c, the GPR91 target engagement was subsequently demonstrated using the designed pharmacodynamic assay. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.091