methyl 3-(4-bromobutoxy)-4-methoxybenzoate | 1609478-00-3

• 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: methyl 3-(4-bromobutoxy)-4-methoxybenzoate
• 英文别名: Methyl 3-(4-bromobutoxy)-4-methoxybenzoate
• CAS: 1609478-00-3
• 化学式: C₁₃H₁₇BrO₄
• 分子量: 317.18
• InChiKey: GLTVZYOEEFEPGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.04
• 重原子数：
  18.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  44.76
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-bromobutoxy)-4-methoxybenzoate 在 potassium tert-butylate 、 四丁基溴化铵 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 20.0~95.0 ℃ 、1.03 MPa 条件下， 反应 0.5h， 生成 3-[4-(1H-imidazol-1-yl)butoxy]-4-methoxy-N-[4-methyl-3-[[4-(pyridin-3-yl)pyrimidin-2-yl]amino]phenyl]benzamide
  参考文献：
  名称：

  Targeting heme Oxygenase-1 with hybrid compounds to overcome Imatinib resistance in chronic myeloid leukemia cell lines

  摘要：

  Heme oxygenase-1 (HO-1) is a cytoprotective enzyme and a survival-enhancing factor in a number of cancers. Chronic myeloid leukemia (CML) is a blood cancer caused by pathological kinase activity of the BCR-ABL protein, currently treated with tyrosine kinase inhibitors (TKIs) such as Imatinib (IM). However, resistance to TKIs persists in a number of patients and HO-1 overexpression has been linked with the induction of chemoresistance in CML. With this in mind, in this study, we designed and synthesized the first series of hybrid compounds obtained by combining the structures of IM, as BCR-ABL inhibitor, with imidazole-based HO-1 inhibitors. We found that many hybrids were able to inhibit the enzymatic activity of both targets and to reduce the viability of CML-IM resistant cells, showing that a single molecular entity may reduce the resistance phenomenon. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.09.048
• 作为产物：
  描述：

  1,4-二溴丁烷 、 3-羟基-4-甲氧基苯甲酸甲酯 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 2.5h， 以94%的产率得到methyl 3-(4-bromobutoxy)-4-methoxybenzoate
  参考文献：
  名称：

  一系列苯甲酰胺作为潜在的多受体抗精神病药的合成，构效关系和生物学评估。

  摘要：

  在本研究中，合成了一系列具有强力多巴胺D2、5-羟色胺5-HT1A和5-HT2A受体特性的苯甲酰胺，并将其评估为潜在的抗精神病药。其中，持有3-（4-（4-（4-（6-氟苯并[d]异恶唑-3-基）-哌啶-1-基）丁氧基] -N-甲基苯甲酰胺（21）及其氟代类似物（22）最佳的药理结合特征。它们不仅表现出对D2、5-HT1A和5-HT2A受体的有效活性，而且对5-HT2C，H1受体和hERG通道的活性低，提示诱导体重增加和QT延长的可能性低。在动物模型中，化合物21和22降低了苯环利定诱导的机能亢进，且僵直诱导的阈值较高。因此，它为进一步的临床前研究提供了潜在的候选者。

  DOI：

  10.1016/j.bmcl.2016.04.087

文献信息

• Design and Synthesis of Systemically Active Metabotropic Glutamate Subtype-2 and -3 (mGlu_2/3) Receptor Positive Allosteric Modulators (PAMs): Pharmacological Characterization and Assessment in a Rat Model of Cocaine Dependence
  作者：Raveendra-Panickar Dhanya、Douglas J. Sheffler、Russell Dahl、Melinda Davis、Pooi San Lee、Li Yang、Hilary Highfield Nickols、Hyekyung P. Cho、Layton H. Smith、Manoranjan S. D’Souza、P. Jeffrey Conn、Andre Der-Avakian、Athina Markou、Nicholas D. P. Cosford

  DOI：10.1021/jm5000563

  日期：2014.5.22

  As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu(2) receptor PAMs and no activity at mGlu(3). Compound optimization led to the identification of potent mGlu(2/3) selective PAMs with no in vitro activity at mGlu(1,4-8) or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu(2) and PAM activity at mGlu(3). The most potent mGlu(2/3) PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu(2/3) PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu(2/3) receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology.
• [EN] METABOTROPIC GLUTAMATE RECEPTOR POSITIVE ALLOSTERIC MODULATORS (PAMS) AND USES THEREOF<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS (PAM) DU RÉCEPTEUR MÉTABOTROPIQUE DU GLUTAMATE ET LEURS UTILISATIONS
  申请人：[en]SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE

  公开号：WO2023122276A1

  公开（公告）日：2023-06-29

  Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor positive allosteric modulators (PAMS), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.