(S)-benzyl-7-(2-cyano-3-(pyridine-4-yl)guanidine)heptanoic acid | 1170230-91-7

• 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: (S)-benzyl-7-(2-cyano-3-(pyridine-4-yl)guanidine)heptanoic acid
• 英文别名: (S)-2-benzyl-7-(2-cyano-3-(pyridine-4-yl)guanidine)heptanoic acid
• CAS: 1170230-91-7
• 化学式: C₂₁H₂₅N₅O₂
• 分子量: 379.462
• InChiKey: QYZZLJWJCMVRLF-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.42
• 重原子数：
  28.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  110.4
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (S)-benzyl-7-(2-cyano-3-(pyridine-4-yl)guanidine)heptanoic acid 、 O-cyclohexyl-hydroxylamine 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以65%的产率得到(S)-2-benzyl-7-(2-cyano-1-(pyridin-4-yl)guanidino)-N-(cyclohexyloxy)heptanamide
  参考文献：
  名称：

  Nicotinamide Phosphoribosyltransferase Inhibitors, Design, Preparation, and Structure–Activity Relationship

  摘要：

  Existing pharmacological inhibitors for nicotinamide phosphoribosyltransferase (NAMPT) are promising therapeutics for treating cancer. By using medicinal and computational chemistry methods, the structure-activity relationship for novel classes of NAMPT inhibitors is described, and the compounds are optimized. Compounds are designed inspired by the NAMPT inhibitor APO866 and cyanoguanidine inhibitor scaffolds. In comparison with recently published derivatives, the new analogues exhibit an equally potent antiproliferative activity in vitro and comparable activity in vivo. The best performing compounds from these series showed subnanomolar antiproliferative activity toward a series of cancer cell lines (compound 15: IC50 0.025 and 0.33 nM, in A2780 (ovarian carcinoma) and MCF-7 (breast), respectively) and potent antitumor in vivo activity in well-tolerated doses in a xenograft model. In an A2780 xenograft mouse model with large tumors (500 mm(3)), compound 15 reduced the tumor volume to one-fifth of the starting volume at a dose of 3 mg/kg administered ip, bid, days 1-9. Thus, compounds found in this study compared favorably with compounds already in the clinic and warrant further investigation as promising lead molecules for the inhibition of NAMPT.

  DOI：

  10.1021/jm4009949
• 作为产物：
  描述：

  4-氨基吡啶 在 N-甲基吗啉 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 6.0h， 生成 (S)-benzyl-7-(2-cyano-3-(pyridine-4-yl)guanidine)heptanoic acid
  参考文献：
  名称：

  Nicotinamide Phosphoribosyltransferase Inhibitors, Design, Preparation, and Structure–Activity Relationship

  摘要：

  Existing pharmacological inhibitors for nicotinamide phosphoribosyltransferase (NAMPT) are promising therapeutics for treating cancer. By using medicinal and computational chemistry methods, the structure-activity relationship for novel classes of NAMPT inhibitors is described, and the compounds are optimized. Compounds are designed inspired by the NAMPT inhibitor APO866 and cyanoguanidine inhibitor scaffolds. In comparison with recently published derivatives, the new analogues exhibit an equally potent antiproliferative activity in vitro and comparable activity in vivo. The best performing compounds from these series showed subnanomolar antiproliferative activity toward a series of cancer cell lines (compound 15: IC50 0.025 and 0.33 nM, in A2780 (ovarian carcinoma) and MCF-7 (breast), respectively) and potent antitumor in vivo activity in well-tolerated doses in a xenograft model. In an A2780 xenograft mouse model with large tumors (500 mm(3)), compound 15 reduced the tumor volume to one-fifth of the starting volume at a dose of 3 mg/kg administered ip, bid, days 1-9. Thus, compounds found in this study compared favorably with compounds already in the clinic and warrant further investigation as promising lead molecules for the inhibition of NAMPT.

  DOI：

  10.1021/jm4009949