3,5-dichloroaniline hydrochloride | 13330-18-2

• 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: 3,5-dichloroaniline hydrochloride
• 英文别名: 3,5-dichloroaniline;hydrochloride
• CAS: 13330-18-2
• 化学式: C₆H₅Cl₂N*ClH
• 分子量: 198.479
• InChiKey: KWRVVTZCOZBFRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.0
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  26
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3,5-dichloroaniline hydrochloride 在 sodium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲苯 、 乙腈 为溶剂， 反应 37.0h， 生成 3-{4-[1-(4-cyclohex-1-enylphenyl)-3-(3,5-dichlorophenyl)ureidomethyl]-benzoylamino}propionic acid
  参考文献：
  名称：

  New β-Alanine Derivatives Are Orally Available Glucagon Receptor Antagonists

  摘要：

  A weak human glucagon receptor antagonist with an IC50 of 7 mu M was initially found by screening of libraries originally targeted to mimic the binding of the glucagon-like peptide (GLP-1) hormone to its receptor. Optimization of this hit for binding affinity for the glucagon receptor led to ligands with affinity in the nanomolar range. In addition to receptor binding, optimization efforts were made to stabilize the molecules against fast metabolic turnover. A potent antagonist of the human human glucagon receptor was obtained that had 17% oral availability in rats with a plasma half-life of 90 min. The major metabolites of this lead were identified and used to further optimize this series with respect to pharmacokinetic properties. This final optimization led to a potent glucagon antagonist that was orally available in rats and dogs and was efficacious in lowering blood glucose levels in a diabetic animal model.

  DOI：

  10.1021/jm058026u

文献信息

• Synthesis, tuberculosis inhibitory activity, and SAR study of N-substituted-phenyl-1,2,3-triazole derivatives
  作者：Marilia S. Costa、Núbia Boechat、Érica A. Rangel、Fernando de C. da Silva、Alessandra M.T. de Souza、Carlos R. Rodrigues、Helena C. Castro、Ivan N. Junior、Maria Cristina S. Lourenço、Solange M.S.V. Wardell、Vitor F. Ferreira

  DOI：10.1016/j.bmc.2006.08.019

  日期：2006.12

  The aim of this work was to describe the synthesis, the in vitro anti-Mycobacterium tuberculosis profile, and the structure-activity relationship (SAR) study of new N-substituted-phenyl-1,2,3-triazole-4-carbaldehydes (3a-l). The reactions of aromatic amine hydrochlorides with diazomalonaldehyde (1) produced several N-substituted-phenyl-1,2,3-triazole-4-carbaldehydes (3a-l) in moderate-to-good yields

  这项工作的目的是描述新型N-取代的苯基-1,2,3-三唑-4-甲醛的合成，体外抗结核分枝杆菌谱以及结构-活性关系（SAR）研究（ 3a-1）。芳族胺盐酸盐与重氮丙二醛（1）的反应以中等至良好的产率产生了几种N-取代的苯基-1,2,3-三唑-4-甲醛（3a-1）。为了研究二氟亚甲基对这些化合物的抗分枝杆菌活性的影响，用DAST氟化三唑可将相应的甲醛化合物以优异的产率转化为新的二氟甲基衍生物（4a-1）。所有化合物的表征均通过分光光度法进行，另外1-（4-甲基苯基）-1,2,3-三唑-4-甲醛通过X射线晶体学测定。已经针对化合物对结核分枝杆菌H37Rv菌株（ATCC 27294）的抑制活性筛选了化合物（3a-1）和（4a-1），并且它们全部都能够抑制细菌的生长。有趣的是，与目前用于治疗结核病的药物相似，3a和3k的MIC值为2.5mug / mL表现出最好的抑制作用。我们的SAR研究表明，氢键
• Synthesis of a novel series of cytotoxic bisindole alkaloids
  作者：Marion Raoul、Corinne Schaeffer、Stéphane Léonce、Alain Pierré、Ghanem Atassi、Reynald Hocquemiller、Guy Lewin

  DOI：10.1016/s0960-894x(00)00600-4

  日期：2001.1

  Original cytotoxic bisindole alkaloids with a 1,2,3,4-tetrahydroquinoline bridge were synthesized by reductive amination with various anilines. The most cytotoxic compounds display a high and dose-dependent cell cycle effect with accumulation in the G1 phase. Influence of substitution of the starting aniline on the reaction and on cytotoxicity of produced dimers was pointed out.

  通过与各种苯胺的还原胺化反应合成具有1,2,3,4-四氢喹啉桥的原始细胞毒性双吲哚生物碱。最具细胞毒性的化合物显示出高剂量依赖性的细胞周期效应，并在G1期积累。指出了起始苯胺的取代对反应和所产生的二聚体的细胞毒性的影响。
• Haloanilino Derivatives of Pyrimidines, Purines, and Purine Nucleoside Analogs: Synthesis and Activity against Human Cytomegalovirus
  作者：Maria Medveczky、Te-Fang Yang、Joseph Gambino、Peter Medveczky、George E. Wright

  DOI：10.1021/jm00010a026

  日期：1995.5

  DNA synthesis by human cytomegalovirus (HCMV)-infected human embryonic lung (HEL) cells in culture. In general, active compounds had moderate to low selectivity for viral vs host cell DNA synthesis. Nucleoside and acyclonucleoside analogs of 2-(3,5-dichloroanilino)purines inhibited both HCMV and cellular DNA synthesis at similar concentrations. 2-Amino-4-chloro-6-(3,5-dichloroanilino)pyrimidine and

  在苯胺环上带有3,4-或3,5-二氯取代基的2-苯胺嘌呤和6-苯胺基嘧啶可抑制人巨细胞病毒（HCMV）感染的人胚肺（HEL）细胞培养的病毒特异性DNA合成。通常，活性化合物对病毒与宿主细胞DNA的合成具有中等至低的选择性。2-（3,5-二氯苯胺基）嘌呤的核苷和无环核苷类似物以相似的浓度抑制HCMV和细胞DNA的合成。2-Amino-4-chloro-6-（3,5-dichloroanilino）pyrimidine和几种相关化合物在产量降低试验中以对HEL细胞无毒的浓度抑制了HCMV生长。
• Verfahren zur Herstellung von m-chlorsubstituierten Anilinen
  申请人：BAYER AG

  公开号：EP0069907A2

  公开（公告）日：1983-01-19

  Die Erfindung betrifft ein Verfahren zur Herstellung von m-chlorsubstituierten Anilinen durch selektive Enthalogenierung von höherchlorierten Anilinen in saurem Medium in Gegenwart von Edelmetallkatalysatoren und in Gegenwart von gegebenenfalls substituierten Phenolen. Die nach dem erfindungsgemäßen Verfahren erhältlichen 3-Chlor- bzw. 3,5-Dichloraniline sind bekannte Zwischenprodukte und können zur Herstellung von Pflanzenschutzmitteln verwendet werden.

  本发明涉及一种制备间氯代苯胺的工艺，该工艺是在酸性介质中，在贵金属催化剂和任选取代的苯酚存在下，对高氯化苯胺进行选择性脱卤反应。 通过本发明的工艺获得的 3-氯或 3,5-二氯苯胺是已知的中间体，可用于生产植物保护剂。
• Synthesis and Pharmacological Evaluation of <i>N</i>-(2,5-Disubstituted phenyl)-<i>N</i>‘-(3-substituted phenyl)-<i>N</i>‘-methylguanidines As <i>N</i>-Methyl-<scp>d</scp>-aspartate Receptor Ion-Channel Blockers
  作者：Lain-Yen Hu、Junqing Guo、Sharad S. Magar、James B. Fischer、Kathleen J. Burke-Howie、Graham J. Durant

  DOI：10.1021/jm970459c

  日期：1997.12.1

  In the mammalian central nervous system, the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors may play an important role in brain diseases such as stroke, brain or spinal cord trauma, epilepsy, and certain neurodegenerative diseases. Compounds which specifically antagonize the actions of the neurotransmitter glutamate at the NMDA receptor ion-channel site offer a novel approach to treating these disorders. CERESTAT (4, aptiganel CNS 1102) is currently undergoing clinical trial for the treatment of traumatic brain injury and stroke. Previously, we reported that analogues of N-1-naphthyl-N'-(3-ethylphenyl)-N'-methylguanidine (4) bound to the NMDA receptor ion-channel site with high potency and selectivity. Recently, molecules active at both a receptors and NMDA receptor sites were investigated. A series of substituted diphenylguanidines 6 which are structurally related to N-1-naphthyl-N'-(3-ethylphenyl)-N'-methylguanidine was prepared. Compounds containing appropriate substitution pattern in one of the phenyl rings of diphenylguanidines displayed high affinity. For example, N-(2,5-dibromophenyl)-N'-(3-ethylphenyl)-N'-methylguanidine (27b, R-2 = R-5 = Br, R-3 = C2H5) exhibited potency at both a receptors and NMDA receptor sites; 27b also showed high efficacy in vivo in a neonatal rat excitotoxicity model. Further studies indicated that substituent effects were important in this compound series, and 2,5-disubstituted phenyl was the preferred substitution pattern for high-affinity binding at NMDA receptor sites. Bromo and methylthio were the optimal substituents for the R-2 and R-5 positions of the 2,5-disubstituted phenyl group, respectively. N-(2-Bromo-5-(methylthio)phenyl)-N'-(3-ethylphenyl)- N'-methylguanidine (34b, R-2 = Br, R-5 = SMe, R-3 = C2H5) was highly active at NMDA receptor sites. We found that the binding affinity of guanidines of type 6 could be further enhanced with the appropriate substitution at R-3. Optimal activity in this series are afforded by 43b and 44b (R-2 = Cl or Br, R-5 = R-3 = SCH3). Both 43b and 44b bound to NMDA receptor sites with high potency and selectivity (K-i vs [H-3]MK-801: 1.87 and 1.65 nM, respectively); these compounds are active in vivo in various animal models of neuroprotection. The structure-activity relationships for-these compounds at the NMDA receptor ion-channel site are discussed.