2-(3-bromothiophen-2-yl)acetaldehyde dimethyl acetal | 1070708-90-5

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 英文名称: 2-(3-bromothiophen-2-yl)acetaldehyde dimethyl acetal
• 英文别名: 2-(3-bromthiophen-2-yl)-acetaldehyddimethylacetal；3-Bromo-2-(2,2-dimethoxyethyl)thiophene
• CAS: 1070708-90-5
• 化学式: C₈H₁₁BrO₂S
• 分子量: 251.144
• InChiKey: SJHYKYRYLLOPBW-UHFFFAOYSA-N

物化性质

• 沸点：
  78 °C(Press: 0.042 Torr)
• 密度：
  1.443±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  46.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-bromothiophen-2-yl)acetaldehyde dimethyl acetal 在 吡啶 、 盐酸 、 苯酐 、 正丁基锂 、 硫酸 、 盐酸羟胺 、 对甲苯磺酸 、 lithium diisopropyl amide 、 原甲酸三甲酯 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 正己烷 、 水 、 乙腈 为溶剂， 反应 30.42h， 生成 methyl 1-benzyl-6'-methoxy-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran]-2'-carboxylate
  参考文献：
  名称：

  Thiophene Bioisosteres of Spirocyclic σ Receptor Ligands: Relationships between Substitution Pattern and σ Receptor Affinity

  摘要：

  On the basis of the 6',7'-dihydrospiro-[piperidine-4,4'-thieno[3,2-c]pyran] framework, a series of more than 30 sigma ligands with versatile substituents in 1-, 2'-, and 6'-position has been synthesized and pharmacologically evaluated in order to find novel structure-affinity relationships. It was found that a cyclohexylmethyl residue at the piperidine N-atom instead of a benzyl moiety led to increased sigma(2) affinity and therefore to decreased sigma(1)/sigma(2), selectivity. Small substituents (e.g., OH, OCH3, CN, CH2OH) in 6'-position adjacent to the O-atom were well tolerated by the sigma(1) receptor. Removal of the substituent in 6'-position resulted in very potent but unselective a ligands (13). A broad range of substituents with various lipophilic and H-bond forming properties was introduced in 2'-position adjacent to the S-atom without loss of a, affinity. However, very polar and basic substituents in both 2'- and 6'-position decreased the a, affinity considerably. It is postulated that the electron density of the thiophene moiety has a big impact on the sigma(1) affinity.

  DOI：

  10.1021/jm300302p
• 作为产物：
  描述：

  (E/Z)-3-bromo-2-(2-methoxyvinyl)thiophene 、 原甲酸三甲酯 在 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以93%的产率得到2-(3-bromothiophen-2-yl)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。
• Thiophene Bioisosteres of Spirocyclic σ Receptor Ligands. 1. N-Substituted Spiro[piperidine-4,4′-thieno[3,2-<i>c</i>]pyrans]
  作者：Christoph Oberdorf、Dirk Schepmann、Jose Miguel Vela、Jose Luis Diaz、Jörg Holenz、Bernhard Wünsch

  DOI：10.1021/jm8007739

  日期：2008.10.23

  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.
• SPIRO ÝPIPERIDINE-4, 4' -THIENO Ý3, 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：EP2170903A1

  公开（公告）日：2010-04-07
• 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.