(R)-N-((S)-2-(2-aminoethylamino)-2-oxo-1-phenylethyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydrospiro[benzo[d] [1,3]oxazine-4,4'-piperidine]-1'-yl)-2-methylbutanamide dihydrochloride

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (R)-N-((S)-2-(2-aminoethylamino)-2-oxo-1-phenylethyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydrospiro[benzo[d] [1,3]oxazine-4,4'-piperidine]-1'-yl)-2-methylbutanamide dihydrochloride
• 英文别名: (2R)-N-[(1S)-2-(2-aminoethylamino)-2-oxo-1-phenylethyl]-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxospiro[3,1-benzoxazine-4,4'-piperidine]-1'-yl)-2-methylbutanamide;hydrochloride
• 化学式: C₃₄H₃₈Cl₂FN₅O₄*2ClH
• 分子量: 743.533
• InChiKey: AAOQXJXMHFUVEW-PSDCGHEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.71
• 重原子数：
  47
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  117
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-(3,4-dichlorophenyl)-pent-4-enoic acid 在 盐酸 、 sodium periodate 、 四氧化锇 、 氯化亚砜 、 水 、 sodium hydride 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 118.33h， 生成 (R)-N-((S)-2-(2-aminoethylamino)-2-oxo-1-phenylethyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydrospiro[benzo[d] [1,3]oxazine-4,4'-piperidine]-1'-yl)-2-methylbutanamide dihydrochloride
  参考文献：
  名称：

  Design, Synthesis, and Optimization of Balanced Dual NK₁/NK₃Receptor Antagonists

  摘要：

  In connection with a program directed at potent and balanced dual NK1/NK3 receptor ligands, a focused exploration of an original class of peptidomimetic derivatives was performed. The rational design and molecular hybridization of a novel phenylalanine core series was achieved to maximize the in vitro affinity and antagonism at both human NK1 and NK3 receptors. This study led to the identification of a new potent dual NK1/NK3 antagonist with pK(i) values of 8.6 and 8.1, respectively.

  DOI：

  10.1021/ml400528y

文献信息

• Design, Synthesis, and Optimization of Balanced Dual NK₁/NK₃Receptor Antagonists
  作者：Stephen Hanessian、Thomas Jennequin、Nicolas Boyer、Vincent Babonneau、Udaykumar Soma、Clotilde Mannoury la Cour、Mark J. Millan、Guillaume De Nanteuil

  DOI：10.1021/ml400528y

  日期：2014.5.8

  In connection with a program directed at potent and balanced dual NK1/NK3 receptor ligands, a focused exploration of an original class of peptidomimetic derivatives was performed. The rational design and molecular hybridization of a novel phenylalanine core series was achieved to maximize the in vitro affinity and antagonism at both human NK1 and NK3 receptors. This study led to the identification of a new potent dual NK1/NK3 antagonist with pK(i) values of 8.6 and 8.1, respectively.