6-methylbenzo[b]thiophene-2-carboxylic acid [1-((S)-1-benzyl-4-{4-[methyl(tetrahydropyran-4-yl)amino]piperidin-1-yl}-4-oxobutylcarbamoyl)cyclopentyl]amide | 1226859-61-5

• 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: 6-methylbenzo[b]thiophene-2-carboxylic acid [1-((S)-1-benzyl-4-{4-[methyl(tetrahydropyran-4-yl)amino]piperidin-1-yl}-4-oxobutylcarbamoyl)cyclopentyl]amide
• 英文别名: 6-methyl-N-[1-[[(2S)-5-[4-[methyl(oxan-4-yl)amino]piperidin-1-yl]-5-oxo-1-phenylpentan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide
• CAS: 1226859-61-5
• 化学式: C₃₈H₅₀N₄O₄S
• 分子量: 658.905
• InChiKey: AKEMMPNUTFLTMX-PMERELPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  47
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-(6-methylbenzo[b]thiophene-2-yl)-3-oxa-1-azaspiro[4,4]non-1-ene-4-one 、 (4S)-4-amino-1-[4-[methyl(oxan-4-yl)amino]piperidin-1-yl]-5-phenylpentan-1-one;hydrochloride 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以70 mg的产率得到6-methylbenzo[b]thiophene-2-carboxylic acid [1-((S)-1-benzyl-4-{4-[methyl(tetrahydropyran-4-yl)amino]piperidin-1-yl}-4-oxobutylcarbamoyl)cyclopentyl]amide
  参考文献：
  名称：

  Structure−Activity Relationships of 6-Methyl-benzo[b]thiophene-2-carboxylic Acid (1-{(S)-1-Benzyl-4-[4-(tetrahydropyran-4-ylmethyl)piperazin-1-yl]butylcarbamoyl}cyclopentyl)amide, Potent Antagonist of the Neurokinin-2 Receptor

  摘要：

  As part of a project aimed at the identification of a series of small, orally available antagonists for the hNK(2) receptor, starting from one of our capped dipeptide libraries, we succeeded in the chemical optimization of the first identified leads, finally producing a class of molecules with significant activity in our animal model after iv administration. We herein report the results of further chemical modifications made to reduce the overall peptide character of this series and the consequent improvement of their in vivo antagonist activity. The present work identified 6-methylbenzo[b]thiophene-2-carboxylic acid (1-{(S)-1-benzyl-4-[4-(tetrahydropyran-4-ylmethyl)piperazin-1-yl]butylcarbamoyl}cyclopentyl)amide (10i), endowed with subnanomolar potency in all the in vitro tests and being highly potent and of long duration upon in vivo testing after both iv and id dosing.

  DOI：

  10.1021/jm100176s