N-(2,5-dichlorophenyl)-2-methylaminoethanol | 321602-12-4

• 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: N-(2,5-dichlorophenyl)-2-methylaminoethanol
• 英文别名: N-(2,5-Dichlorophenyl)-2-methylamino-ethanol；2-(2,5-dichloro-N-methylanilino)ethanol
• CAS: 321602-12-4
• 化学式: C₉H₁₁Cl₂NO
• 分子量: 220.098
• InChiKey: ULDVPCBNHYDVOT-UHFFFAOYSA-N

物化性质

• 沸点：
  337.9±32.0 °C(Predicted)
• 密度：
  1.331±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(2,5-dichlorophenyl)-2-methylaminoethanol 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 N,N'-dimethyl-N-(2,5-dichlorophenyl)ethylenediamine
  参考文献：
  名称：

  Synthesis, Screening, and Molecular Modeling of New Potent and Selective Antagonists at the α_1d Adrenergic Receptor

  摘要：

  In the present study, more than 75 compounds structurally related to BMY 7378 have been designed and synthesized. Structural variations of each part of the reference molecule have been introduced, obtaining highly selective ligands for the aid adrenergic receptor. The molecular determinants for selectivity at this receptor are essentially, held by the phenyl substituent in the phenylpiperazine moiety. The integration of an extensive SAR analysis with docking simulations using the rhodopsin-based models of the three alpha(1)-AR subtypes and of the 5-HT1A receptor provides significant insights into the characterization of the receptor binding sites as well as into the molecular determinants of ligand selectivity at the alpha(1d)-AR and the 5-HT1A receptors. The results of multiple copies simultaneous search (MCSS) on the substituted phenylpiperazines together with those of manual docking of compounds BAN 7378 and 69 into the putative binding sites of the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR, and the 5-HT1A receptors suggest that the phenylpiperazine moiety would dock into a site formed by amino acids in helices 3, 4, 5, 6 and extracellular loop 2, (E2), whereas the spirocyclic ring of the ligand docks into a site formed by amino acids of helices 1, 2, 3, and 7. This docking mode is consistent with the SAR data produced in this work. Furthermore, the binding site of the imide moiety does not allow for the simultaneous involvement of the two carbonyl oxygen atoms in H-bonding, interactions, consistent with the SAR data, in particular with the results obtained with the lactam derivative 128. The results of docking simulations also suggest that the second and third extracellular loops may act as selectivity filters for the substituted phenylpiperazines. The most potent and selective compounds for alpha(1d) adrenergic receptor, i.e., 69 (Rec 26D/038) and 128 (Rec 26D/073), are characterized by the presence of the 2,5-dichlorophenylpiperazine moiety.

  DOI：

  10.1021/jm030944+
• 作为产物：
  描述：

  2,5-二氯苯胺 在 甲酸 、 三乙胺 作用下， 反应 34.0h， 生成 N-(2,5-dichlorophenyl)-2-methylaminoethanol
  参考文献：
  名称：

  Synthesis, Screening, and Molecular Modeling of New Potent and Selective Antagonists at the α_1d Adrenergic Receptor

  摘要：

  In the present study, more than 75 compounds structurally related to BMY 7378 have been designed and synthesized. Structural variations of each part of the reference molecule have been introduced, obtaining highly selective ligands for the aid adrenergic receptor. The molecular determinants for selectivity at this receptor are essentially, held by the phenyl substituent in the phenylpiperazine moiety. The integration of an extensive SAR analysis with docking simulations using the rhodopsin-based models of the three alpha(1)-AR subtypes and of the 5-HT1A receptor provides significant insights into the characterization of the receptor binding sites as well as into the molecular determinants of ligand selectivity at the alpha(1d)-AR and the 5-HT1A receptors. The results of multiple copies simultaneous search (MCSS) on the substituted phenylpiperazines together with those of manual docking of compounds BAN 7378 and 69 into the putative binding sites of the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR, and the 5-HT1A receptors suggest that the phenylpiperazine moiety would dock into a site formed by amino acids in helices 3, 4, 5, 6 and extracellular loop 2, (E2), whereas the spirocyclic ring of the ligand docks into a site formed by amino acids of helices 1, 2, 3, and 7. This docking mode is consistent with the SAR data produced in this work. Furthermore, the binding site of the imide moiety does not allow for the simultaneous involvement of the two carbonyl oxygen atoms in H-bonding, interactions, consistent with the SAR data, in particular with the results obtained with the lactam derivative 128. The results of docking simulations also suggest that the second and third extracellular loops may act as selectivity filters for the substituted phenylpiperazines. The most potent and selective compounds for alpha(1d) adrenergic receptor, i.e., 69 (Rec 26D/038) and 128 (Rec 26D/073), are characterized by the presence of the 2,5-dichlorophenylpiperazine moiety.

  DOI：

  10.1021/jm030944+

文献信息

• [EN] CYCLIC AMIDES AND IMIDES HAVING SELECTIVE ANTAGONIST ACTIVITY AT ALPHA-1D ADRENERGIC RECEPTOR<br/>[FR] AMIDES ET IMIDES CYCLIQUES POSSEDANT UNE ACTIVITE ANTAGONISTE SELECTIVE AU NIVEAU DU RECEPTEUR ADRENERGIQUE 1D
  申请人：RECORDATI CHEM PHARM

  公开号：WO2001005765A1

  公开（公告）日：2001-01-25

  Compounds (I) R and R1 independently = H or C1-C4 alkyl or together = (CH2)2-6, n=0 or 1, ...... is a single or a double bond, A=CO or CH2, A1 represents a CO or CH2 or CH, each R3 independently = H or C1-C4 alkyl, B is B1 or B2 (B2); Y=N or CH, R2 = halogen, C1-C4 alkyl or CN, R5 = halogen, C1-C4 alkyl, polyfluoroalkyl or NO2, R6 = H or halogen, m is 1 to 3, Z = O, S, NH or NMe) interact selectively with the α1D subtype of the α1 adrenergic receptor. This selectively makes these compounds useful agents in tissues particularly rich in α1D adrenergic receptors, thus useful in reducing contractility of an unstable urinary bladder, in the treatment and prevention of atherosclerosis as they are inhibitors of noradrenaline-mediated cell proliferation in smooth muscles, and in reducing vascular adrenergic tone. The preparation of these compounds, their enantiomers, diastereoisomers, N-oxides and pharmaceutically acceptable salts, and pharmaceutical compositions containing them are also claimed.

  化合物（I）中，R和R1分别为H或C1-C4烷基，或者在一起为（CH2）2-6，n=0或1，......为单键或双键，A=CO或CH2，A1代表CO或CH2或CH，每个R3独立地为H或C1-C4烷基，B为B1或B2（B2）；Y=N或CH，R2=卤素，C1-C4烷基或CN，R5=卤素，C1-C4烷基，多氟烷基或NO2，R6=H或卤素，m为1到3，Z=O，S，NH或NMe）与α1D亚型的α1肾上腺素受体选择性相互作用。这种选择性使得这些化合物在α1D肾上腺素受体特别丰富的组织中成为有用的药物，因此可用于减少不稳定的膀胱的收缩性，在动脉粥样硬化的治疗和预防中，因为它们是平滑肌中去甲肾上腺素介导的细胞增殖的抑制剂，以及减少血管肾上腺素张力。还声明了这些化合物、它们的对映体、对映异构体、N-氧化物和药学上可接受的盐的制备以及含有它们的制药组合物。
• Verfahren zur Herstellung von Farbstoffzwischenprodukten
  申请人：CIBA-GEIGY AG

  公开号：EP0370953A2

  公开（公告）日：1990-05-30

  Ein Verfahren zur Herstellung von Verbindungen der Formel welches dadurch gekennzeichnet ist, dass man eine Verbindung der Formel mit einem Halogenierungsmittel in Gegenwart einer Verbindung der Formel NA      (2a) umsetzt, und worin die Symbole die im Anspruch 1 angegebene Bedeutung haben, wird beschrieben. Die nach dem Verfahren erhältlichen Verbindungen stellen wertvolle Kupplungskomponenten für die Synthese von kationischen Farbstoffen dar.

  一种制备式化合物的工艺，其特征在于 其特征在于式化合物 与一种卤化剂在一种式化合物存在下进行反应 NA (2a) 其中符号的含义如权利要求 1 所述。通过该工艺得到的化合物是合成阳离子染料的重要偶联组分。
• CYCLIC AMIDES AND IMIDES HAVING SELECTIVE ANTAGONIST ACTIVITY AT ALPHA-1D ADRENERGIC RECEPTOR
  申请人：RECORDATI INDUSTRIA CHIMICA E FARMACEUTICA S.p.a.

  公开号：EP1200406B1

  公开（公告）日：2004-11-24
• Synthesis, Screening, and Molecular Modeling of New Potent and Selective Antagonists at the α_1d Adrenergic Receptor
  作者：Amedeo Leonardi、Daniela Barlocco、Federica Montesano、Giorgio Cignarella、Gianni Motta、Rodolfo Testa、Elena Poggesi、Michele Seeber、Pier G. De Benedetti、Francesca Fanelli

  DOI：10.1021/jm030944+

  日期：2004.4.1

  In the present study, more than 75 compounds structurally related to BMY 7378 have been designed and synthesized. Structural variations of each part of the reference molecule have been introduced, obtaining highly selective ligands for the aid adrenergic receptor. The molecular determinants for selectivity at this receptor are essentially, held by the phenyl substituent in the phenylpiperazine moiety. The integration of an extensive SAR analysis with docking simulations using the rhodopsin-based models of the three alpha(1)-AR subtypes and of the 5-HT1A receptor provides significant insights into the characterization of the receptor binding sites as well as into the molecular determinants of ligand selectivity at the alpha(1d)-AR and the 5-HT1A receptors. The results of multiple copies simultaneous search (MCSS) on the substituted phenylpiperazines together with those of manual docking of compounds BAN 7378 and 69 into the putative binding sites of the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR, and the 5-HT1A receptors suggest that the phenylpiperazine moiety would dock into a site formed by amino acids in helices 3, 4, 5, 6 and extracellular loop 2, (E2), whereas the spirocyclic ring of the ligand docks into a site formed by amino acids of helices 1, 2, 3, and 7. This docking mode is consistent with the SAR data produced in this work. Furthermore, the binding site of the imide moiety does not allow for the simultaneous involvement of the two carbonyl oxygen atoms in H-bonding, interactions, consistent with the SAR data, in particular with the results obtained with the lactam derivative 128. The results of docking simulations also suggest that the second and third extracellular loops may act as selectivity filters for the substituted phenylpiperazines. The most potent and selective compounds for alpha(1d) adrenergic receptor, i.e., 69 (Rec 26D/038) and 128 (Rec 26D/073), are characterized by the presence of the 2,5-dichlorophenylpiperazine moiety.