(R)-2-benzyl-7-(2-cyano-1-(pyridin-4-yl)guanidino)-N-(cyclohexyloxy)heptanamide | 1170235-60-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-2-benzyl-7-(2-cyano-1-(pyridin-4-yl)guanidino)-N-(cyclohexyloxy)heptanamide
• 英文别名: (R)-2-benzyl-7-(2-cyano-3-(pyridin-4-yl)guanidino)-N-(cyclohexyloxy)heptanamide；(2R)-2-benzyl-7-[[(cyanoamino)-(pyridin-4-ylamino)methylidene]amino]-N-cyclohexyloxyheptanamide
• CAS: 1170235-60-5
• 化学式: C₂₇H₃₆N₆O₂
• 分子量: 476.622
• InChiKey: GBUFIRFNSCTGLY-HSZRJFAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  35
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)hexanesulfonyl chloride 在 N-甲基吗啉 、 sodium hydride 、 sodium cyanoborohydride 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 22.0h， 生成 (R)-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