EF 7412 | 221452-76-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: EF 7412
• 英文别名: Ethanesulfonamide, N-(3-(4-(4-(tetrahydro-1,3-dioxo-1H-pyrrolo(1,2-C)imidazol-2(3H)-yl)butyl)-1-piperazinyl)phenyl)-；N-[3-[4-[4-(1,3-dioxo-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazol-2-yl)butyl]piperazin-1-yl]phenyl]ethanesulfonamide
• CAS: 221452-76-2
• 化学式: C₂₂H₃₃N₅O₄S
• 分子量: 463.601
• InChiKey: APHPLOYRLDEZMD-UHFFFAOYSA-N

物化性质

• 沸点：
  630.6±65.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  四氢-1H-吡咯并[1,2-c]咪唑-1,3(2H)-二酮 在 palladium on activated charcoal 吡啶 、 氢气 、 sodium hydride 、 三乙胺 作用下， 以 甲醇 、 丙酮 、 乙腈 为溶剂， 反应 25.0h， 生成 EF 7412
  参考文献：
  名称：

  Design and synthesis of 2-[4-[4-(m-(ethylsulfonamido)-phenyl)piperazin-1-yl]butyl]-1,3-dioxoperhydropyrrolo[1,2-c]imidazole (EF-7412) using neural networks. A selective derivative with mixed antagonist properties

  摘要：

  A test series of 32 phenylpiperazines III with affinity for 5-HT1A and alpha(1) receptors was subjected to QSAR analysis using artificial neural networks (ANNs), in order to get insight into the structural requirements that are responsible for 5-HT1A/alpha(1) selectivity. Good models and predictive power were obtained for 5-HT1A and alpha(1) receptors. A comparison of these models gives information for the design of the new ligand EF-7412 (5-HT1A:K-i (nM)= 27; alpha(1):K-i (nM) > 1000). This derivative displayed affinity for dopamine D-2 receptor (K-i=22 nM) and is selective for all other receptor examined (5-HT2A, 5-HT3, 5-HT3, 5-HT4 and Bz). EF-7412 acts an antagonist in vivo in pre- and postsynaptic 5-MT1A receptor sites and as an antagonist in dopamine D-2 receptor. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00254-1

文献信息

• Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 5. Study of the Physicochemical Influence of the Pharmacophore on 5-HT_1A/α₁-Adrenergic Receptor Affinity:  Synthesis of a New Derivative with Mixed 5-HT_1A/D₂ Antagonist Properties
  作者：María L. López-Rodríguez、M. José Morcillo、Esther Fernández、Esther Porras、Luis Orensanz、M Eugenia Beneytez、Jorge Manzanares、Jose Angel Fuentes

  DOI：10.1021/jm000929u

  日期：2001.1.1

  In this paper we have designed and synthesized a test series of 32 amide arylpiperazine derivatives VI in order to gain insight into the physicochemical influence of the pharmacophores of 5-HT1A and alpha (1)-adrenergic receptors. The training set was designed applying a fractional factorial design using six physicochemical descriptors. The amide moiety is a bicyclohydantoin or a diketopiperazine (X = -(CH2)(3)-, -(CH2)(4)-; m = 0, 1), the spacer length is 3 or 4 methylene units, which are the optimum values for both receptors, and the aromatic substituent R occupies the ortho- or meta-position and has been selected from a database of 387 substituents using the EDISFAR program. The 5-HT1A and alpha (1)-adrenergic receptor binding affinities of synthesized compounds VI (1-32) have been determined. This data set has been used to derive classical quantitative structure-activity relationships (QSAR) and neural-networks models for both receptors (following paper). A comparison of these models gives information for the design of the new ligand EF-7412 (46) (5-HT1A: K-i = 27 nM; alpha (1): K-i > 1000 nM). This derivative displays affinity for the dopamine D-2 receptor (K-i = 22 nM) and is selective versus all other receptors examined (5-HT2A, 5-HT3, 5-HT4 and Bz; K-i > 1000 nM). EF-7412 (46) acts as an antagonist in vivo in pre- and postsynaptic 5-HT1A receptor sites and; as an antagonist in the dopamine D-2 receptor. Thus, EF-7412 (46) is a derivative with mixed 5-HT1A/D-2 antagonist properties and this derivative could be useful as a pharmacological tool.
• Methods of Suppressing Appetite by the Administration of Antagonists of the Serotonin HTR1a or HTR2b Receptors or Inhibitors of TPH2
  申请人：Karsenty Gerard

  公开号：US20120115778A1

  公开（公告）日：2012-05-10

  Methods for treating eating disorders associated with excessive weight gain, suppressing appetite, reducing body weight, or treating obesity in an animal by administering one or more antagonists of the serotonin Htr1a or Htr2b receptor, or a Tph2 inhibitor are provided, or combinations thereof.
• [EN] PROCESS FOR OBTAINING 2-[4-[4-(m- ETHYLSULFONAMIDO-PHENYL) PIPERAZINE-1-YL] BUTYL]-1,3- DIOXOPERHYDROYRROLO [1,2-c]IMIDAZOL<br/>[ES] PROCEDIMIENTO PARA LA OBTENCION DEL 2-[4-[4-(m- ETILSULFONAMIDOFENIL) PIPERAZIN-1-IL] BUTIL]-1,3- DIOXOPERHIDROPIRROLO [1,2-c]IMIDAZOL<br/>[FR] PROCEDE D'OBTENTION DU 2-[4-[4-(m- ETHYLSULFONAMIDOPHENYL) PIPERAZINE-1-YL] BUTYL]-1,3- DIOXOPERHYDROPYRROLO [1,2-c]IMIDAZOL
  申请人：UNIVERSIDAD COMPLUTENSE DE MADRID

  公开号：WO1999015527A1

  公开（公告）日：1999-04-01

  (EN) The present invention relates to a new process for producing 2-[4-[4-($i(m)- ethylsulfonamidophenyl) piperazine-1-yl] butyl]-1,3- dioxoperhydropyrrolo [1,2-$i(c)]imidazol (1, EF-7412), which is a syntesis compound having a therapeutical interest due to its antagonist character for the receptor 5-HT1A. This new process obviates the difficulties of the priorly described process for the preparation of such product and enables to fabricate the desired product in a much simpler synthetic sequence and with higher yields.(ES) La presente invención tiene per objeto un nuevo procedimiento de obtención del 2-[4-[4-($i(m)- etilsulfonamidofenil) piperazin-1-il] butil]-1,3- dioxoperhidropirrolo [1,2-$i(c)]imidazol (1, EF-7412), compuesto de síntesis con interés terapéutico por su carácter antagonista del receptor 5-HT1A. Este nuevo procedimiento obvia las dificultades del método descrito previamente para su preparación ya que llega al producto deseado en una secuencia sintética de mayor simplicidad y con rendimientos superiores.(FR) L'invention concerne un nouveau procédé d'obtention du 2-[4-[4-( $i(m)-éthylsulfonamidophényl) pipérazine-1-yl] butyl]-1,3- dioxoperhydropyrrolo [1,2-$i(c)]imidazol (1, EF-7412), composé de synthèse présentant un intérêt thérapeutique lié à son caractère antagoniste du récepteur 5-HT1A. Ce nouveau procédé permet de surmonter les difficultés rencontrées auparavant lors de la préparation, car ce procédé permet d'obtenir le produit souhaité en une séquence synthétique de plus grande simplicité et avec des rendements supérieurs.
• [EN] METHODS OF SUPPRESSING APPETITE BY THE ADMINISTRATION OF ANTAGONISTS OF THE SEROTONIN HTR1a or HTR2b RECEPTORS OR INHIBITORS OF TPH2<br/>[FR] PROCÉDÉS DE SUPPRESSION DE L'APPÉTIT PAR L'ADMINISTRATION D'ANTAGONISTES DES RÉCEPTEURS HTR1A OU HTR2B DE LA SÉROTONINE OU D'INHIBITEURS DE TPH2
  申请人：UNIV COLUMBIA

  公开号：WO2011009012A1

  公开（公告）日：2011-01-20

  Methods for treating eating disorders associated with excessive weight gain, suppressing appetite, reducing body weight, or treating obesity in an animal by administering one or more antagonists of the serotonin Htr1a or Htr2b receptor, or a Tph2 inhibitor are provided, or combinations thereof.
• Design and synthesis of 2-[4-[4-(m-(ethylsulfonamido)-phenyl)piperazin-1-yl]butyl]-1,3-dioxoperhydropyrrolo[1,2-c]imidazole (EF-7412) using neural networks. A selective derivative with mixed antagonist properties
  作者：María L López-Rodríguez、M JoséMorcillo、Esther Fernández、M Luisa Rosado、Luis Orensanz、M Eugenia Beneytez、Jorge Manzanares、JoséA Fuentes、Klaus-Jürgen Schaper

  DOI：10.1016/s0960-894x(99)00254-1

  日期：1999.6

  A test series of 32 phenylpiperazines III with affinity for 5-HT1A and alpha(1) receptors was subjected to QSAR analysis using artificial neural networks (ANNs), in order to get insight into the structural requirements that are responsible for 5-HT1A/alpha(1) selectivity. Good models and predictive power were obtained for 5-HT1A and alpha(1) receptors. A comparison of these models gives information for the design of the new ligand EF-7412 (5-HT1A:K-i (nM)= 27; alpha(1):K-i (nM) > 1000). This derivative displayed affinity for dopamine D-2 receptor (K-i=22 nM) and is selective for all other receptor examined (5-HT2A, 5-HT3, 5-HT3, 5-HT4 and Bz). EF-7412 acts an antagonist in vivo in pre- and postsynaptic 5-MT1A receptor sites and as an antagonist in dopamine D-2 receptor. (C) 1999 Elsevier Science Ltd. All rights reserved.