(8S)-2-(hydroxymethyl)-N,N,3-trimethyl-8-(2-methylphenyl)-7,8-dihydro-6H-pyrano[2,3-e]benzimidazole-5-carboxamide | 1172118-69-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: (8S)-2-(hydroxymethyl)-N,N,3-trimethyl-8-(2-methylphenyl)-7,8-dihydro-6H-pyrano[2,3-e]benzimidazole-5-carboxamide
• CAS: 1172118-69-2
• 化学式: C₂₂H₂₅N₃O₃
• 分子量: 379.459
• InChiKey: UUCUJQQVYFYOSR-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  67.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (8S)-2-(hydroxymethyl)-N,N,3-trimethyl-8-(2-methylphenyl)-7,8-dihydro-6H-pyrano[2,3-e]benzimidazole-5-carboxamide 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 生成 (8S)-2-(chloromethyl)-N,N,3-trimethyl-8-(2-methylphenyl)-3,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamide
  参考文献：
  名称：

  Tetrahydrochromenoimidazoles作为钾竞争性酸阻滞剂（P-CABs）：其抗分泌特性及其对hERG通道的亲和力的结构-活性关系†

  摘要：

  钾竞争性酸阻滞剂（P-CAB）构成了治疗与酸有关的疾病的新的治疗选择，这些疾病与疾病相关的疾病广泛且构成重大的经济负担。使用容易获得的候选物4制备对映体纯的四氢色氮咪唑（BYK 405879）作为起始原料或Noyori酮的不对称还原是关键反应。建立了关于5-羧酰胺和8-芳基残基对体外活性，Ghosh Schild大鼠体内酸抑制和对hERG通道的亲和力影响的综合SAR。此外，通过瘘管犬的24 h pH测量，检查了最有希望的目标化合物的抗分泌作用的功效和持续时间，与Ghosh Schild大鼠相比，观察到了明显不同的SAR。鉴定了几种与候选物4具有可比性的四氢色氮咪唑。

  DOI：

  10.1021/jm100040c
• 作为产物：
  描述：

  在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以55%的产率得到(8S)-2-(hydroxymethyl)-N,N,3-trimethyl-8-(2-methylphenyl)-7,8-dihydro-6H-pyrano[2,3-e]benzimidazole-5-carboxamide
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of potential metabolites of the potassium-competitive acid blocker BYK405879

  摘要：

  Four potential metabolites of the potassium-competitive acid blocker BYK 405879 (1) were synthesized which might be formed in vivo by enzymatic oxidation of the pyran moiety or the methyl groups attached to the (hetero) aromatic system. In all cases, the oxidation of the parent compound 1 was accompanied by a significant loss of pharmacological activity and by a decrease in lipophilicity. The target compounds 6, 14, 20, and 21 constitute valuable tool substances for the investigation of the metabolic fate of BYK 405879 (1). (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.04.070

文献信息

• Tetrahydrochromenoimidazoles as Potassium-Competitive Acid Blockers (P-CABs): Structure−Activity Relationship of Their Antisecretory Properties and Their Affinity toward the hERG Channel
  作者：Andreas M. Palmer、Vittoria Chiesa、Anja Schmid、Gabriela Münch、Burkhard Grobbel、Peter J. Zimmermann、Christof Brehm、Wilm Buhr、Wolfgang-Alexander Simon、Wolfgang Kromer、Stefan Postius、Jürgen Volz、Dietmar Hess

  DOI：10.1021/jm100040c

  日期：2010.5.13

  Potassium-competitive acid blockers (P-CABs) constitute a new therapeutic option for the treatment of acid-related diseases that are widespread and constitute a significant economical burden. Enantiomerically pure tetrahydrochromenoimidazoles were prepared using the readily available candidate 4 (BYK 405879) as starting material or the Noyori asymmetric reduction of ketones as key reaction. A comprehensive

  钾竞争性酸阻滞剂（P-CAB）构成了治疗与酸有关的疾病的新的治疗选择，这些疾病与疾病相关的疾病广泛且构成重大的经济负担。使用容易获得的候选物4制备对映体纯的四氢色氮咪唑（BYK 405879）作为起始原料或Noyori酮的不对称还原是关键反应。建立了关于5-羧酰胺和8-芳基残基对体外活性，Ghosh Schild大鼠体内酸抑制和对hERG通道的亲和力影响的综合SAR。此外，通过瘘管犬的24 h pH测量，检查了最有希望的目标化合物的抗分泌作用的功效和持续时间，与Ghosh Schild大鼠相比，观察到了明显不同的SAR。鉴定了几种与候选物4具有可比性的四氢色氮咪唑。
• Synthesis and pharmacological evaluation of potential metabolites of the potassium-competitive acid blocker BYK405879
  作者：Andreas Marc Palmer、Gabriela Münch、Burkhard Grobbel、Wolfgang Kromer

  DOI：10.1016/j.tetlet.2009.04.070

  日期：2009.7

  Four potential metabolites of the potassium-competitive acid blocker BYK 405879 (1) were synthesized which might be formed in vivo by enzymatic oxidation of the pyran moiety or the methyl groups attached to the (hetero) aromatic system. In all cases, the oxidation of the parent compound 1 was accompanied by a significant loss of pharmacological activity and by a decrease in lipophilicity. The target compounds 6, 14, 20, and 21 constitute valuable tool substances for the investigation of the metabolic fate of BYK 405879 (1). (c) 2009 Elsevier Ltd. All rights reserved.