2-{3-[1-(cyclohexylmethyl)-4-hydroxypiperidin-4-yl]-2-thienyl}acetaldehyde dimethyl acetal | 1070709-06-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-{3-[1-(cyclohexylmethyl)-4-hydroxypiperidin-4-yl]-2-thienyl}acetaldehyde dimethyl acetal
• 英文别名: 2-[3-(1-(cyclohexylmethyl)-4-hydroxypiperidin-4-yl)thiophen-2-yl]acetaldehyddimethylacetal；1-(Cyclohexylmethyl)-4-[2-(2,2-dimethoxyethyl)thiophen-3-yl]piperidin-4-ol
• CAS: 1070709-06-6
• 化学式: C₂₀H₃₃NO₃S
• 分子量: 367.553
• InChiKey: DSFHKVULPGQJJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  70.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-{3-[1-(cyclohexylmethyl)-4-hydroxypiperidin-4-yl]-2-thienyl}acetaldehyde dimethyl acetal 在 对甲苯磺酸 、 原甲酸三甲酯 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以68%的产率得到1-(cyclohexylmethyl)-6'-methoxy-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran]
  参考文献：
  名称：

  Thiophene Bioisosteres of Spirocyclic σ Receptor Ligands. 1. N-Substituted Spiro[piperidine-4,4′-thieno[3,2-c]pyrans]

  摘要：

  Herein, the synthesis and pharmacological evaluation of thiophene bioisosteres of the highly potent spirocyclic benzopyran 1 are detailed. The synthesis of 1-benzyl-6'-methoxy-6',7'-dihydrospiro[piperidine-4,4'-thieno[3.2-c]pyran] (2a) was performed starting with 3-bromothiophene (3). After introduction of the acetaldehyde substructure (7), halogen metal exchange, addition of 1-benzylpiperidin-4-one, and cyclization led to the spirocyclic thienopyran 2a. The removal of the benzyl group afforded the secondary amine 2f, which was substituted with various residues. With respect to a, affinity the N-benzyl derivative 2a, the N-cyclohexylmethyl derivative 2d, and the N-p-fluorobenzyl derivative 2i represent the most potent compounds of this series binding with K-i values of 0.32, 0.29, and 0.62 nM, respectively. Electronic properties of the substituents have only little impact on sigma(1) affinity. The most potent sigma(1) ligands display high selectivity against sigma(2), 5-HT1A, 5-HT6, 5-HT7, alpha(1A), alpha(2), and NMDA receptors. The activity of 2a in the mouse capsaicin assay seems to indicate sigma(1) antagonistic activity.

  DOI：

  10.1021/jm8007739
• 作为产物：
  描述：

  (E/Z)-3-bromo-2-(2-methoxyvinyl)thiophene 在 对甲苯磺酸 正丁基锂 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 27.8h， 生成 2-{3-[1-(cyclohexylmethyl)-4-hydroxypiperidin-4-yl]-2-thienyl}acetaldehyde dimethyl acetal
  参考文献：
  名称：

  WO2008/155132

  摘要：

  公开号：

文献信息

• spiro[piperidine-4,4'-thieno[3,2-c]pyran] derivatives and related compounds as inhibitors of the sigma receptor for the treatment of psychosis
  申请人：Laboratorios del Dr. Esteve S.A.

  公开号：EP2020414A1

  公开（公告）日：2009-02-04

  The present invention relates to compounds having pharmacological activity towards the sigma (σ) receptor, and more particularly to some thieno-pyrano-pyrazole derivatives, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy and prophylaxis, in particular for the treatment of psychosis or pain.

  本发明涉及对 sigma（σ）受体具有药理活性的化合物，特别是一些噻吩并吡喃并吡唑衍生物，涉及此类化合物的制备工艺，涉及包含这些化合物的药物组合物，还涉及它们在治疗和预防中的用途，特别是用于治疗精神病或疼痛。
• SPIRO[PIPERIDINE-4,4' -THIENO[3, 2-C]PYRAN]DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE SIGMA RECEPTOR FOR THE TREATMENT OF PSYCHOSIS
  申请人：Laboratorios del. Dr. Esteve, S.A.

  公开号：EP2170903B1

  公开（公告）日：2012-09-05
• SPIRO [PIPERIDINE-4- 4' -THIENO [3,2-C] PYRAN] DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE SIGMA RECEPTOR FOR THE TREATMENT OF PSYCHOSIS
  申请人：Oberdorf Christoph

  公开号：US20100190813A1

  公开（公告）日：2010-07-29

  The present invention relates to compounds having pharmacological activity towards the sigma (σ) receptor, and more particularly to some thieno-pyrano-pyrazole derivatives, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy and prophylaxis, in particular for the treatment of psychosis or pain.
• [EN] SPIRO [PIPERIDINE-4, 4' -THIENO [3, 2-C] PYRAN] DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE SIGMA RECEPTOR FOR THE TREATMENT OF PSYCHOSIS<br/>[FR] DÉRIVÉS DE SPIRO[PIPERIDIN-4,4'-THIENO[3,2-C]PYRAN] ET COMPOSÉS ASSOCIÉS UTILISÉS COMME INHIBITEURS DU RÉCEPTEUR SIGMA POUR LE TRAITEMENT DE LA PSYCHOSE
  申请人：ESTEVE LABOR DR

  公开号：WO2008155132A1

  公开（公告）日：2008-12-24

  [EN] The present invention relates to compounds having pharmacological activity towards the sigma (s) receptor, and more particularly to some thieno-pyrano-pyrazole derivatives, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy and prophylaxis, in particular for the treatment of psychosis or pain.
  [FR] La présente invention concerne des composés ayant une activité pharmacologique vis-à-vis du récepteur sigma (s), et plus particulièrement quelques dérivés de thiéno-pyrano-pyrazole, des procédés de préparation de ces composés, des compositions pharmaceutiques les comprenant, et leur utilisation en thérapie et en prophylaxie, en particulier pour le traitement de la psychose ou de la douleur.