1-bromo-4-(1-bromoamino)toluene | 748166-19-0

• 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: 1-bromo-4-(1-bromoamino)toluene
• 英文别名: 2-Bromo-2-(4-bromophenyl)acetonitrile
• CAS: 748166-19-0
• 化学式: C₈H₅Br₂N
• 分子量: 274.942
• InChiKey: ZKBJAUMNUCTIDB-UHFFFAOYSA-N

物化性质

• 沸点：
  301.6±27.0 °C(Predicted)
• 密度：
  1.886±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-bromo-4-(1-bromoamino)toluene 在 silver nitrate 作用下， 以 乙腈 为溶剂， 反应 5.0h， 以84%的产率得到4-溴苯甲酰腈
  参考文献：
  名称：

  通过形成硝酸氰醇中间体方便地合成芳酰基氰化物的新方法

  摘要：

  用AgNO 3处理α-溴芳基乙腈可生成氰醇硝酸盐中间体，该中间体可轻松消除亚硝酸并形成羰基键，从而以高收率或高收率提供芳酰基氰化物。

  DOI：

  10.1016/j.tetlet.2008.06.034
• 作为产物：
  描述：

  对溴苯乙腈 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 氯仿 为溶剂， 反应 48.0h， 以21%的产率得到1-bromo-4-(1-bromoamino)toluene
  参考文献：
  名称：

  苯并[b]噻吩-2-羧酰胺作为新型阿片受体激动剂，具有强效镇痛作用和减少便秘

  摘要：

  目前，对具有较少副作用的新型镇痛剂存在显着未满足的需求。在这项研究中，我们对先前在人工智能 (AI) 虚拟筛选中发现的命中化合物进行了结构修饰，并发现了具有新结构支架的强效镇痛剂苯并[b]噻吩-2-甲酰胺类似物（化合物25 ）。我们研究了化合物25介导的阿片受体信号通路，发现这种外消旋化合物通过环磷酸腺苷 (cAMP) 和 β-arrestin-2 介导的通路激活 mu-阿片受体，具有很强的效力和功效，并伴随着伤害感受素- orphanin FQ 阿片肽和 δ-阿片受体通过 cAMP 通路，效力较弱。化合物25在热刺激疼痛（ED 50值为 127.1 ± 34.65 μg/kg）和炎症诱导的异常性疼痛模型中引起有效的镇痛作用，其胃肠道转运抑制和镇痛耐受性低于吗啡。总体而言，这项研究揭示了一种降低副作用风险的新型镇痛剂。

  DOI：

  10.1016/j.ejmech.2022.114728

文献信息

• JAK激酶抑制剂及其应用
  申请人：上海翔锦生物科技有限公司

  公开号：CN108341814B

  公开（公告）日：2021-09-03

  本发明公开了一种具有下述通式(I)的化合物。本发明还公开了包含该化合物的JAK激酶抑制剂及该化合物在制备治疗JAK相关性疾病的药物中的应用。本发明的JAK激酶抑制剂，能够抑制参与多种信号传导的JAK1、JAK2、JAK3和TYK2激酶的生物活性，能有效地临床治疗各种炎症性疾病以及由JAK介导信号转导驱动的各种疾病，应用前景非常广阔。。
• Enantioselective Mannich-Type Reactions to Construct Trifluoromethylthio-Containing Tetrasubstituted Carbon Stereocenters <i>via</i> Asymmetric Dual-Reagent Catalysis
  作者：Lijun Xu、Hongyu Wang、Changwu Zheng、Gang Zhao

  DOI：10.1002/adsc.201700321

  日期：2017.9.4

  stereocenters bearing both a trifluoromethylthio (SCF3) group and a cyano group has been realized, through asymmetric organophosphine-catalyzed Mannich-type reactions. The products were obtained in high yields and moderate to high enantioselectivities. Two diastereoisomers could be isolated from each reaction (overall 25 examples), rendering this approach a viable opportunity for molecular diversity generation

  通过不对称有机膦催化的曼尼希型反应，已经实现了构建同时具有三氟甲硫基（SCF 3）基团和氰基基团的四取代碳立构中心的方法。以高收率和中等至高对映选择性获得产物。可以从每个反应中分离出两个非对映异构体（总共25个实例），从而使该方法成为分子多样性产生和相关药物候选物生物活性改善的可行机会。
• 2,4,4,6-Tetrabromocyclohexa-2,5-dienone in the presence of triphenylphosphine as a specific reagent for nucleophilic substitution in cyanohydrins
  作者：Elena D. Matveeva、Tatyana A. Podrugina、Elena V. Tishkovskaya、Nikolai S. Zefirov

  DOI：10.1070/mc2003v013n06abeh001830

  日期：2003.1

  A convenient method for the synthesis of alpha-bromonitriles from aliphatic cyanohydrins using the 2,4,4,6-tetrabromocyclohexa-2,5-dienone complex with triphenylphosphine was developed.
• Histamine H1 receptor ligands
  作者：Krzysztof Walczyński、Roman Guryn、Obbe P Zuiderveld、Ming-Qiang Zhang、Henk Timmerman

  DOI：10.1016/s0014-827x(00)00087-2

  日期：2000.11

  New 2-[2-(phenylamino)thiazol-4-yl]ethanamine and 2-(2-benzhydrylthiazol-4-yl)ethanamine derivatives were prepared and tested in vitro as H-1 receptor antagonists. The compounds with 2-phenylamino substitution with meta-halide substituents at the phenyl ring, showed weak H-1-antagonistic activity (pA(2): 4.62-5.04) and this activity was completely lost in the case of meta-methyl substituent (pA(2) < 4). When the phenylamino group was replaced by benzhydryl groups of classic antihistamines, the resulting compounds exhibited slightly improved H-1-antagonistic activity (at the meta-position pA(2): 6.38-6.15; at the para-position pA(2): 6.04-5.87). (C) 2000 Elsevier Science S.A. All rights reserved.
• Potential Modes of Interaction of 9-Aminomethyl-9,10-dihydroanthracene (AMDA) Derivatives with the 5-HT_2A Receptor: A Ligand Structure-Affinity Relationship, Receptor Mutagenesis and Receptor Modeling Investigation
  作者：Scott P. Runyon、Philip D. Mosier、Bryan L. Roth、Richard A. Glennon、Richard B. Westkaemper

  DOI：10.1021/jm800771x

  日期：2008.11.13

  The effects of 3-position substitution of 9-aminomethyl-9,10-dihydroanthracene (AMDA) on 5-HT2A receptor affinity were determined and compared to a parallel series of DOB-like 1-(2,5-dimethoxyphenyl)-2-aminopropanes substituted at the 4-position. The results were interpreted within the context of 5-HT2A receptor models that suggest that members of the DOB-like series call bind to the receptor in two distinct modes that correlate with the compounds' functional activity. Automated ligand docking and molecular dynamics suggest that all of the AMDA derivatives, the parent of which is a 5-HT2A antagonist, bind in a fashion analogous to that for the sterically demanding antagonist DOB-like compounds. The failure of the F340(6.52)L mutation to adversely affect the affinity of AMDA and the 3-bromo derivative is consistent with the proposed modes of orientation. Evaluation of ligand-receptor complex models suggest that a valine/threonine exchange between the 5-HT2A and D-2 receptors may be the origin of selectivity for AMDA and two substituted derivatives.