methyl 1H-imidazo[4.5-c]pyridine-2-carboxylate | 1199773-69-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: methyl 1H-imidazo[4.5-c]pyridine-2-carboxylate
• 英文别名: Methyl 1H-imidazo[4,5-C]pyridine-2-carboxylate；methyl 3H-imidazo[4,5-c]pyridine-2-carboxylate
• CAS: 1199773-69-7
• 化学式: C₈H₇N₃O₂
• 分子量: 177.162
• InChiKey: WHHFXCZPABOCAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 1H-imidazo[4.5-c]pyridine-2-carboxylate 、 (4-(苯基磺酰基)苯基)甲胺 在 三甲基铝 作用下， 以 甲苯 为溶剂， 反应 4.67h， 以6.3%的产率得到N-{[4-(benzenesulfonyl)phenyl]methyl}-3H-imidazo[4,5-c]pyridine-2-carboxamide
  参考文献：
  名称：

  Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors

  摘要：

  Crystal structures of several urea- and thiourea-derived compounds in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein were utilized to design a potent amide-containing inhibitor bearing an aza-indole moiety (7, Nampt BC IC50 = 9.0 nM, A2780 cell proliferation IC50 = 10 nM). The Nampt-7 cocrystal structure was subsequently obtained and enabled the design of additional amide-containing inhibitors which incorporated various other fused 6,5-heterocyclic moieties and biaryl sulfone or sulfonamide motifs. Additional modifications of these molecules afforded many potent biaryl sulfone-containing Nampt inhibitors which also exhibited favorable in vitro ADME properties (microsomal and hepatocyte stability, MOCK permeability, plasma protein binding). An optimized compound (58) was a potent inhibitor of multiple cancer cell lines (IC50 <10 nM vs U251, HT1080, PC3, MiaPaCa2, and HCT116 lines), displayed acceptable mouse PK properties (F = 41%, CL = 52.4 mL/min/kg), and exhibited robust efficacy in a U251 mouse xenograft model.

  DOI：

  10.1021/jm4008664
• 作为产物：
  描述：

  3,4-二氨基吡啶 在 sodium carbonate 、 三氟乙酸 作用下， 以 甲醇 、 水 为溶剂， 反应 48.0h， 生成 methyl 1H-imidazo[4.5-c]pyridine-2-carboxylate
  参考文献：
  名称：

  Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors

  摘要：

  Crystal structures of several urea- and thiourea-derived compounds in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein were utilized to design a potent amide-containing inhibitor bearing an aza-indole moiety (7, Nampt BC IC50 = 9.0 nM, A2780 cell proliferation IC50 = 10 nM). The Nampt-7 cocrystal structure was subsequently obtained and enabled the design of additional amide-containing inhibitors which incorporated various other fused 6,5-heterocyclic moieties and biaryl sulfone or sulfonamide motifs. Additional modifications of these molecules afforded many potent biaryl sulfone-containing Nampt inhibitors which also exhibited favorable in vitro ADME properties (microsomal and hepatocyte stability, MOCK permeability, plasma protein binding). An optimized compound (58) was a potent inhibitor of multiple cancer cell lines (IC50 <10 nM vs U251, HT1080, PC3, MiaPaCa2, and HCT116 lines), displayed acceptable mouse PK properties (F = 41%, CL = 52.4 mL/min/kg), and exhibited robust efficacy in a U251 mouse xenograft model.

  DOI：

  10.1021/jm4008664

文献信息

• [EN] NOVEL COMPOUNDS AND COMPOSITIONS FOR THE INHIBITION OF NAMPT<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS POUR L'INHIBITION DE NAMPT
  申请人：FORMA THERAPEUTICS INC

  公开号：WO2012031197A1

  公开（公告）日：2012-03-08

  The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below:

  本发明涉及用于抑制NAMPT的化合物和组合物，以及它们的合成、应用和解毒剂。本发明的一个示例化合物如下所示：
• HIV-INTEGRASE INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND METHODS FOR THEIR USE
  申请人：HU Qiyue

  公开号：US20080221154A1

  公开（公告）日：2008-09-11

  Bicyclic hydroxamate compounds represented by the Formula I: are described. The bicyclic hydroxamate compounds and compositions containing those compounds may be used to inhibit or modulate an enzyme activity of HIV Integrase and to treat HIV mediated diseases and conditions.

  描述了由公式I表示的二环羟肟化合物。这些二环羟肟化合物和含有这些化合物的组合物可用于抑制或调节HIV整合酶的酶活性，并用于治疗HIV介导的疾病和病况。
• NOVEL COMPOUNDS AND COMPOSITIONS FOR THE INHIBITION OF NAMPT
  申请人：Bair Kenneth W.

  公开号：US20140294805A1

  公开（公告）日：2014-10-02

  The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below:

  本发明涉及用于抑制NAMPT的化合物和组合物，其合成，应用和解毒剂。本发明的一个示例化合物如下所示：
• Compounds and compositions for the inhibition of NAMPT
  申请人：Forma TM, LLC

  公开号：US10272072B2

  公开（公告）日：2019-04-30

  The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below:

  本发明涉及抑制 NAMPT 的化合物和组合物、其合成、应用和解毒剂。本发明的一种说明性化合物如下所示：
• Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors
  作者：Xiaozhang Zheng、Paul Bauer、Timm Baumeister、Alexandre J. Buckmelter、Maureen Caligiuri、Karl H. Clodfelter、Bingsong Han、Yen-Ching Ho、Nikolai Kley、Jian Lin、Dominic J. Reynolds、Geeta Sharma、Chase C. Smith、Zhongguo Wang、Peter S. Dragovich、Janet Gunzner-Toste、Bianca M. Liederer、Justin Ly、Thomas O’Brien、Angela Oh、Leslie Wang、Weiru Wang、Yang Xiao、Mark Zak、Guiling Zhao、Po-wai Yuen、Kenneth W. Bair

  DOI：10.1021/jm4008664

  日期：2013.8.22

  Crystal structures of several urea- and thiourea-derived compounds in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein were utilized to design a potent amide-containing inhibitor bearing an aza-indole moiety (7, Nampt BC IC50 = 9.0 nM, A2780 cell proliferation IC50 = 10 nM). The Nampt-7 cocrystal structure was subsequently obtained and enabled the design of additional amide-containing inhibitors which incorporated various other fused 6,5-heterocyclic moieties and biaryl sulfone or sulfonamide motifs. Additional modifications of these molecules afforded many potent biaryl sulfone-containing Nampt inhibitors which also exhibited favorable in vitro ADME properties (microsomal and hepatocyte stability, MOCK permeability, plasma protein binding). An optimized compound (58) was a potent inhibitor of multiple cancer cell lines (IC50 <10 nM vs U251, HT1080, PC3, MiaPaCa2, and HCT116 lines), displayed acceptable mouse PK properties (F = 41%, CL = 52.4 mL/min/kg), and exhibited robust efficacy in a U251 mouse xenograft model.