(S)-(-)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)chloroacetamide | 220831-97-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (S)-(-)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)chloroacetamide
• 英文别名: 2-chloro-N-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide
• CAS: 220831-97-0
• 化学式: C₁₂H₁₄ClNO
• mdl: MFCD03150772
• 分子量: 223.702
• InChiKey: SLQUITRGZWAZBX-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (S)-(-)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)chloroacetamide 、 (2R)-3-(2-methylbenzothiazol-5-yloxy)-1-piperazinylpropan-2-ol 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 N-((1S)-1,2,3,4-tetrahydronaphthyl)-2-{4-[(2R)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}acetamide
  参考文献：
  名称：

  New fatty acid oxidation inhibitors with increased potency lacking adverse metabolic and electrophysiological properties

  摘要：

  New inhibitors of palmitoylCoA oxidation were synthesized based on a structurally novel lead, CVT-3501 (1). Investigation of structure-activity relationships was conducted with respect to potency of inhibition of cardiac mitochondrial palmitoylCoA oxidation and metabolic stability. Potent and metabolically stable analogues 33, 42, and 43 were evaluated in vitro for cytochrome P450 inhibition and potentially adverse electrophysiological effects. Compound 33 was also found to have favorable pharmacokinetic properties in rat. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.093
• 作为产物：
  描述：

  (S)-(+)-1,2,3,4-四氢-1-萘胺 、 氯乙酰氯 在 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以100%的产率得到(S)-(-)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)chloroacetamide
  参考文献：
  名称：

  1-Aryl-4-[(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)alkyl]piperazines and Their Analogues:  Influence of the Stereochemistry of the Tetrahydronaphthalen-1-yl Nucleus on 5-HT_1A Receptor Affinity and Selectivity versus α₁ and D₂ Receptors. 5

  摘要：

  Some 1-aryl-4-[(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-propyl]piperazines and their alkylamino and alkylamido analogues, previously studied as 5-HT1A ligands, were prepared in enantiomerically pure form, and their absolute configuration was det;ermined by chemical correlation or by chiroptical properties. They were evaluated for in vitro 5-HT1A, D-2, and alpha(1) receptor affinity by radioligand binding assays, to study the influence of the chiral carbon atom of the tetrahydronaphthalene nucleus on the 5-HT1A affinity and selectivity. Results indicated that, as regarding the 5-HT1A receptor affinity, there was no difference in affinity between (-)- and (+)-enantiomers as well as the racemate of each compound. The stereochemistry, instead, influenced the selectivity: all (-)-enantiomers displayed affinity values higher than those of (+)-isomers at D-2 receptors, and conversely, all (+)-enantiomers displayed affinity values higher than those of (-)-isomers at alpha(1) receptors. As a result of this trend, it is not possible to predict the isomer with a better selectivity profile. However, compounds (S)-(+)-2, (S)-(+)-4, and (R)-(+)-6 displayed high affinity for the 5-HT1A receptor (IC50 values ranging between 7.0 and 2.3 nM) and good selectivity (greater than or equal to 250-fold) versus both D-2 and alpha(1) receptors. Furthermore, compounds (S)-(+)-4 and (R)-(-)-4 were submitted to the [S-35]GTP gamma S binding assay for a preliminary evaluation of their intrinsic activity on the 5-HT1A receptor.

  DOI：

  10.1021/jm980420n

文献信息

• 1-Aryl-4-[(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)alkyl]piperazines and Their Analogues:  Influence of the Stereochemistry of the Tetrahydronaphthalen-1-yl Nucleus on 5-HT_1A Receptor Affinity and Selectivity versus α₁ and D₂ Receptors. 5
  作者：Roberto Perrone、Francesco Berardi、Nicola A. Colabufo、Marcello Leopoldo、Vincenzo Tortorella

  DOI：10.1021/jm980420n

  日期：1999.2.1

  Some 1-aryl-4-[(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-propyl]piperazines and their alkylamino and alkylamido analogues, previously studied as 5-HT1A ligands, were prepared in enantiomerically pure form, and their absolute configuration was det;ermined by chemical correlation or by chiroptical properties. They were evaluated for in vitro 5-HT1A, D-2, and alpha(1) receptor affinity by radioligand binding assays, to study the influence of the chiral carbon atom of the tetrahydronaphthalene nucleus on the 5-HT1A affinity and selectivity. Results indicated that, as regarding the 5-HT1A receptor affinity, there was no difference in affinity between (-)- and (+)-enantiomers as well as the racemate of each compound. The stereochemistry, instead, influenced the selectivity: all (-)-enantiomers displayed affinity values higher than those of (+)-isomers at D-2 receptors, and conversely, all (+)-enantiomers displayed affinity values higher than those of (-)-isomers at alpha(1) receptors. As a result of this trend, it is not possible to predict the isomer with a better selectivity profile. However, compounds (S)-(+)-2, (S)-(+)-4, and (R)-(+)-6 displayed high affinity for the 5-HT1A receptor (IC50 values ranging between 7.0 and 2.3 nM) and good selectivity (greater than or equal to 250-fold) versus both D-2 and alpha(1) receptors. Furthermore, compounds (S)-(+)-4 and (R)-(-)-4 were submitted to the [S-35]GTP gamma S binding assay for a preliminary evaluation of their intrinsic activity on the 5-HT1A receptor.
• New fatty acid oxidation inhibitors with increased potency lacking adverse metabolic and electrophysiological properties
  作者：Dmitry O. Koltun、Timothy A. Marquart、Kevin D. Shenk、Elfatih Elzein、Yuan Li、Marie Nguyen、Suresh Kerwar、Dewan Zeng、Nancy Chu、Daniel Soohoo、Jia Hao、Victoria Y. Maydanik、David A. Lustig、Khing-Jow Ng、Heather Fraser、Jeffery A. Zablocki

  DOI：10.1016/j.bmcl.2003.09.093

  日期：2004.1

  New inhibitors of palmitoylCoA oxidation were synthesized based on a structurally novel lead, CVT-3501 (1). Investigation of structure-activity relationships was conducted with respect to potency of inhibition of cardiac mitochondrial palmitoylCoA oxidation and metabolic stability. Potent and metabolically stable analogues 33, 42, and 43 were evaluated in vitro for cytochrome P450 inhibition and potentially adverse electrophysiological effects. Compound 33 was also found to have favorable pharmacokinetic properties in rat. (C) 2003 Elsevier Ltd. All rights reserved.