1-<(2S)-2-(4-nitrophenyl)-2-(methylamino)ethyl>pyrrolidine | 158059-81-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-<(2S)-2-(4-nitrophenyl)-2-(methylamino)ethyl>pyrrolidine
• 英文别名: (S)-1-<2-(methylamino)-2-(4-nitrophenyl)ethyl>pyrrolidine；(1S)-N-methyl-1-(4-nitrophenyl)-2-pyrrolidin-1-ylethanamine
• CAS: 158059-81-5
• 化学式: C₁₃H₁₉N₃O₂
• 分子量: 249.313
• InChiKey: KYUONRYHQWDVRC-CYBMUJFWSA-N

物化性质

• 沸点：
  377.8±32.0 °C(predicted)
• 密度：
  1.154±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  61.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-<(2S)-2-(4-nitrophenyl)-2-(methylamino)ethyl>pyrrolidine 在 platinum(IV) oxide 吡啶 、 盐酸 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 25.0 ℃ 、310.27 kPa 条件下， 反应 34.0h， 生成 N-methyl-N-<(1S)-1-(4-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl>-3,4-dichlorophenylacetamide
  参考文献：
  名称：

  Isothiocyanate-Substituted .kappa.-Selective Opioid Receptor Ligands Derived from N-Methyl-N-[(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl]phenylacetamide

  摘要：

  The synthesis of isothiocyanate-substituted K-selective opioid ligands derived from N-methyl-N-[(1S)-1-phenyl-2- (1-pyrrolidinyl)ethyl]ethyl]phenylacetamide (8) and their effects in radioligand displacement assays are reported. Ligands 3-5 with the S-absolute configuration were prepared with the isothiocyanate functionality at the 2-, 3-, and 4-positions in the phenylacetamide aromatic ring. The 2-isothiocyanato-4,5-dichlorophenylacetamide 6 was prepared to evaluate the effect of 4,5-dichloro substitution in the same aromatic ring as the 2-isothiocyanate function. N-Methyl-N-[(1S)-1-(4-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl]-3,4-dichlorophenylacetamide (7), with the 4-isothiocyanate function in the 1-phenyl ring, was prepared for comparison with the other compounds in the series. Of the prepared ligands, 7 and 8 (IC(50)s similar or equal to 1.4-1.8 nM) were approximately equal in affinity with 2 (ICI-199,441), followed by 3 and 6. All of these compounds were more kappa-selective than 2, as well. The binding characteristics of 8 show that the previously reported 4,5-dichloro substitution is not required for high affinity and kappa-selectivity. All of the synthesized isothiocyanate-substituted ligands irreversibly inhibited radioligand binding to guinea pig brain membrane preparations, including compound 2 (ICI-199,441) which had no isothiocyanate functionality.

  DOI：

  10.1021/jm00044a006
• 作为产物：
  描述：

  乙酮,2-溴-1-(4-硝基苯基)-,肟 在 吡啶 、 盐酸 、 硼烷四氢呋喃络合物 、 dimethyl sulfide borane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 82.0h， 生成 1-<(2S)-2-(4-nitrophenyl)-2-(methylamino)ethyl>pyrrolidine
  参考文献：
  名称：

  Isothiocyanate-Substituted .kappa.-Selective Opioid Receptor Ligands Derived from N-Methyl-N-[(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl]phenylacetamide

  摘要：

  The synthesis of isothiocyanate-substituted K-selective opioid ligands derived from N-methyl-N-[(1S)-1-phenyl-2- (1-pyrrolidinyl)ethyl]ethyl]phenylacetamide (8) and their effects in radioligand displacement assays are reported. Ligands 3-5 with the S-absolute configuration were prepared with the isothiocyanate functionality at the 2-, 3-, and 4-positions in the phenylacetamide aromatic ring. The 2-isothiocyanato-4,5-dichlorophenylacetamide 6 was prepared to evaluate the effect of 4,5-dichloro substitution in the same aromatic ring as the 2-isothiocyanate function. N-Methyl-N-[(1S)-1-(4-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl]-3,4-dichlorophenylacetamide (7), with the 4-isothiocyanate function in the 1-phenyl ring, was prepared for comparison with the other compounds in the series. Of the prepared ligands, 7 and 8 (IC(50)s similar or equal to 1.4-1.8 nM) were approximately equal in affinity with 2 (ICI-199,441), followed by 3 and 6. All of these compounds were more kappa-selective than 2, as well. The binding characteristics of 8 show that the previously reported 4,5-dichloro substitution is not required for high affinity and kappa-selectivity. All of the synthesized isothiocyanate-substituted ligands irreversibly inhibited radioligand binding to guinea pig brain membrane preparations, including compound 2 (ICI-199,441) which had no isothiocyanate functionality.

  DOI：

  10.1021/jm00044a006

文献信息

• .kappa. Opioid Receptor Selective Affinity Labels: Electrophilic Benzeneacetamides as .kappa.-Selective Opioid Antagonists
  作者：An-Chih Chang、Akira E. Takemori、William H. Ojala、William B. Gleason、Philip S. Portoghese

  DOI：10.1021/jm00052a008

  日期：1994.12

  high binding affinity and selectivity of the 3-isothiocyanate 3 (DIPPA) to kappa opioid receptors, wash studies have suggested that this involves covalent binding. In the mouse tail-flick assay, the 3- and 4-substituted isomers (3 and 5, respectively) produced long-lasting antagonism of the antinociceptive effect of the kappa opioid agonist, (+/-)-trans-2-(3,4-dichlorophenyl)-N-methyl-N-[2-(1-pyrrolidinyl)

  合成了2-（3,4-二氯苯基）-N-甲基-N- [1-（3-或4-取代的苯基）-2-（1-吡咯烷基）乙基]-乙酰胺3-6作为κ选择性亲和力标记并评估阿片样物质的活性。在平滑肌制剂中，非亲电子母体化合物（+）-S-2和亲和标记3-6表现为kappa激动剂，因为它们被norbinaltorphimine（norBNI）强烈拮抗。除了3-异硫氰酸酯3（DIPPA）对κ阿片受体的高结合亲和力和选择性外，洗涤研究还表明这涉及共价结合。在小鼠甩尾试验中，3-和4-取代的异构体（分别为3和5）对kappa阿片激动剂（+/-）-trans-2-（3 ，4-二氯苯基）-N-甲基-N- [2-（1-吡咯烷基）环己基]乙酰胺（（+/-）-U50，488）。相反，在甩尾试验中，非亲电子母体化合物（+）-S-2和富马酸酯衍生物4没有拮抗活性。在小鼠腹部拉伸试验中，DIPPA（3）和4-异硫氰酸酯5的剂量基本不同，也