(2R)-N-[1-(4-methyl-3-pentenyl)piperidin-4-yl]-2-[(1S,3S)-3-(4-trifluoromethylphenyl)sulfonylaminocyclopentyl]-2-hydroxy-2-phenylacetamide

• 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: (2R)-N-[1-(4-methyl-3-pentenyl)piperidin-4-yl]-2-[(1S,3S)-3-(4-trifluoromethylphenyl)sulfonylaminocyclopentyl]-2-hydroxy-2-phenylacetamide
• 英文别名: (2R)-2-hydroxy-N-[1-(4-methylpent-3-enyl)piperidin-4-yl]-2-phenyl-2-[(1S,3S)-3-[[4-(trifluoromethyl)phenyl]sulfonylamino]cyclopentyl]acetamide
• 化学式: C₃₁H₄₀F₃N₃O₄S
• 分子量: 607.738
• InChiKey: GLIYEFHXPLOCJH-XXJPWZBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (2R,5R)-2-(tert-butyl)-5-phenyl-1,3-dioxolan-4-one 在 sodium hydroxide 、 sodium tetrahydroborate 、 sodium azide 、 三乙胺 、 三苯基膦 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 环己烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.5h， 生成 (2R)-N-[1-(4-methyl-3-pentenyl)piperidin-4-yl]-2-[(1S,3S)-3-(4-trifluoromethylphenyl)sulfonylaminocyclopentyl]-2-hydroxy-2-phenylacetamide
  参考文献：
  名称：

  Discovery of a muscarinic M 3 receptor antagonist with high selectivity for M 3 over M 2 receptors among 2-[(1 S ,3 S )-3-sulfonylaminocyclopentyl]phenylacetamide derivatives

  摘要：

  In the course of developing a metabolically stable M-3 receptor antagonist from the prototype antagonist, J-104129 (1), introduction of certain substituents into the cyclopentane ring of 1 was found to be effective not only in improving metabolic stability but also in greatly enhancing the subtype selectivity. Among the cyclopentane analogues, sulfonamide derivatives (10f) and (10g) displayed 160- and 310-fold selectivity for M-3 over M-2 receptors, and both were significantly more selective than the prototype antagonist (120-fold). Subsequent derivatization of the sulfonamide series led to the highly selective M-3 receptor antagonists (10h, 10i and 10j) with >490-fold selectivity for M-3 over M-2 receptors. Among them, p-nitrophenylsulfonamide (J-107320, 10h) exhibited 1 100-fold selectivity for M-3 receptors (K-i = 2.5 nM) over M-2 receptors (K-i = 2800 nM) in the human muscarinic receptor binding assay using [H-3]-NMS as a radio ligand. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00008-0