N-[[4-(1-isopropylpyrazol-4-yl)sulfonylphenyl]methyl]furo[2,3-c]pyridine-2-carboxamide | 1454285-17-6

• 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: N-[[4-(1-isopropylpyrazol-4-yl)sulfonylphenyl]methyl]furo[2,3-c]pyridine-2-carboxamide
• 英文别名: N-(4-((1-isopropyl-1H-pyrazol-4-yl)sulfonyl)benzyl)furo[2,3-c]pyridine-2-carboxamide；N-[[4-(1-propan-2-ylpyrazol-4-yl)sulfonylphenyl]methyl]furo[2,3-c]pyridine-2-carboxamide
• CAS: 1454285-17-6
• 化学式: C₂₁H₂₀N₄O₄S
• 分子量: 424.48
• InChiKey: GCBARIQAGXVYET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (4-((1-Isopropyl-1H-pyrazol-4-yl)sulfonyl)phenyl)methanamine 、 呋喃并[2,3-c]吡啶-2-羧酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 N-[[4-(1-isopropylpyrazol-4-yl)sulfonylphenyl]methyl]furo[2,3-c]pyridine-2-carboxamide
  参考文献：
  名称：

  Identification of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with no evidence of CYP3A4 time-dependent inhibition and improved aqueous solubility

  摘要：

  Herein we report the optimization efforts to ameliorate the potent CYP3A4 time-dependent inhibition (TDI) and low aqueous solubility exhibited by a previously identified lead compound from our NAMPT inhibitor program (1, GNE-617). Metabolite identification studies pinpointed the imidazopyridine moiety present in 1 as the likely source of the TDI signal, and replacement with other bicyclic systems was found to reduce or eliminate the TDI finding. A strategy of reducing the number of aromatic rings and/or lowering cLogD(7.4) was then employed to significantly improve aqueous solubility. These efforts culminated in the discovery of 42, a compound with no evidence of TDI, improved aqueous solubility, and robust efficacy in tumor xenograft studies. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.026

文献信息

• [EN] AMIDO-BENZYL SULFONE AND SULFONAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS SULFONAMIDES ET SULFONES AMIDO-BENZYLIQUES
  申请人：GENENTECH INC

  公开号：WO2013127268A1

  公开（公告）日：2013-09-06

  Disclosed are certain amido-benzyl sulfone and sulfonamide compounds, pharmaceutical compositions comprising such compounds, land methods of treatment using such compounds.

  披露了某些氨基苯甲基砜和磺胺化合物，包括这些化合物的药物组合物，以及使用这些化合物的治疗方法。