N-[(1R,2S,5S)-5-acetyl-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide | 1126601-80-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-[(1R,2S,5S)-5-acetyl-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide
• 英文别名: N-[(1R,2S,5S)-5-acetyl-2-[(5-chloro-1H-indole-2-carbonyl)amino]cyclohexyl]-5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridine-2-carboxamide
• CAS: 1126601-80-6
• 化学式: C₂₅H₂₈ClN₅O₃S
• 分子量: 514.048
• InChiKey: RYAPFHFYVVEULH-ADLFWFRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-{(1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-[methoxy(methyl)carbamoyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide 、 甲基锂 以 四氢呋喃 为溶剂， 以60%的产率得到N-[(1R,2S,5S)-5-acetyl-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide
  参考文献：
  名称：

  Discovery of N-[(1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-(dimethylcarbamoyl)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide hydrochloride: A novel, potent and orally active direct inhibitor of factor Xa

  摘要：

  In the early 1990's, we reported on the low-molecular selective fXa inhibitor DX-9065a having two amidino groups. However, it had poor oral bioavailability due to its strong basic amidino groups. To obtain fXa inhibitors with improved oral bioavailability, we investigated various non-amidino fXa inhibitors and finally discovered cis-1,2-diaminocyclohexane derivative 4c to have potent fXa inhibition, promising anticoagulant activity, and good oral bioavailability, compared with amidino compound DX-9065a. In addition, we will discuss the influence of the third substituent on the cyclohexane ring on anti-fXa activity, anticoagulant activity, PK profile, and lipophilicity. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.12.037