N-isopropyl-3,4-dimethoxyaniline

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-isopropyl-3,4-dimethoxyaniline
• 英文别名: 3,4-dimethoxy-N-propan-2-ylaniline
• 化学式: C₁₁H₁₇NO₂
• mdl: MFCD11142911
• 分子量: 195.261
• InChiKey: PSDXIPQYSORWJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2-氯甲基)-甲基哌啶盐酸盐 、 N-isopropyl-3,4-dimethoxyaniline 在 sodium amide 作用下， 以 甲苯 为溶剂， 反应 0.5h， 以16%的产率得到N-isopropyl-3,4-dimethoxy-N-(2-(1-methylpiperidin-2-yl)ethyl)aniline
  参考文献：
  名称：

  Rational Design and Synthesis of Thioridazine Analogues as Enhancers of the Antituberculosis Therapy

  摘要：

  Tuberculosis, caused by Mycobacterium tuberculosis, is still one of the leading infectious diseases globally. Therefore, novel approaches are needed to face this disease. Efflux pumps are known to contribute to the emergence of M tuberculosis drug resistance. Thioridazine has shown good anti-TB properties both in vitro and in vivo, likely due to its capacity to inhibit efflux mechanisms. Here we report the design and synthesis of a number of putative efflux inhibitors inspired by the structure of thioridazine. Compounds were evaluated for their in vitro and ex vivo activity against M. tuberculosis H37Rv. Compared to the parent molecule, some of the compounds synthesized showed higher efflux inhibitory capacity, less cytotoxicity, and a remarkable synergistic effect with anti-TB drugs both in vitro and in human macrophages, demonstrating their potential to be used as coadjuvants for the treatment of tuberculosis.

  DOI：

  10.1021/acs.jmedchem.5b00428
• 作为产物：
  描述：

  4-叠氮基-1,2-二甲氧基苯 、 异丙基溴化镁 以 乙醚 为溶剂， 反应 0.5h， 以87%的产率得到N-isopropyl-3,4-dimethoxyaniline
  参考文献：
  名称：

  通过将格氏试剂添加到芳基叠氮化物中来制备单-N-烷基苯胺的新颖而有效的方法

  摘要：

  单Ñ当各种芳族叠氮化物用在室温下的烷基卤化镁反应，短的反应时间内以高产率得到烷基苯胺。

  DOI：

  10.1016/s0040-4039(99)01771-2

文献信息

• [EN] PHENETHYLAMIDE DERIVATIVES AND THEIR HETEROCYCLIC ANALOGUES<br/>[FR] DÉRIVÉS DE PHÉNÉTHYLAMIDE ET LEURS ANALOGUES HÉTÉROCYCLIQUES
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2010044054A1

  公开（公告）日：2010-04-22

  The invention relates to novel phenethylamide derivatives and their heterocyclic analogues of formula (I), wherein A, B, R1, R2 and R3 are as described in the application, and to the use of such compounds, or of pharmaceutically acceptable salts of such compounds, as medicaments, especially as orexin receptor antagonists.

  这项发明涉及新型苯乙酰胺衍生物及其异环类似物，其化学式为(I)，其中A、B、R1、R2和R3如申请中所述，并且涉及将这种化合物或这种化合物的药用可接受盐用作药物，特别是促进睡眠的药物受体拮抗剂。
• Discovery of Conformationally Restricted Human Glutaminyl Cyclase Inhibitors as Potent Anti-Alzheimer’s Agents by Structure-Based Design
  作者：Van-Hai Hoang、Van T. H. Ngo、Minghua Cui、Nguyen Van Manh、Phuong-Thao Tran、Jihyae Ann、Hee-Jin Ha、Hee Kim、Kwanghyun Choi、Young-Ho Kim、Hyerim Chang、Stephani Joy Y. Macalino、Jiyoun Lee、Sun Choi、Jeewoo Lee

  DOI：10.1021/acs.jmedchem.9b00751

  日期：2019.9.12

  analyses indicated that conformationally restrained inhibitors demonstrated much improved QC inhibition in vitro compared to nonrestricted analogues, and several selected compounds demonstrated desirable therapeutic activity in an AD mouse model. The conformational analysis of a representative inhibitor indicated that the inhibitor appeared to maintain the Z-E conformation at the active site, as it

  阿尔茨海默氏病（AD）是一种无法治愈的进行性神经退行性疾病，其发病机理不能由一个单一因素定义，而是由多种因素组成。因此，呼吁寻求替代方法来解决AD的多方面问题。在潜在的替代目标中，我们的目标是集中在谷氨酰胺环化酶（QC）上，该酶可降低AD患者大脑中β-淀粉样蛋白的毒性焦磷酸型。基于原型抑制剂1的假定的活性构象，开发了一系列的N-取代的硫脲，脲和α-取代的酰胺衍生物。结构-活性关系分析表明，与非限制性类似物相比，构象受限的抑制剂在体外表现出大大改善的QC抑制作用，几种选择的化合物在AD小鼠模型中显示出理想的治疗活性。对代表性抑制剂的构象分析表明，该抑制剂似乎在活性位点保持ZE构象，因为它对其有效活性至关重要。
• N-치환된 티오우레아 또는 우레아 유도체 및 이를 유효성분으로 함유하는 글루타미닐 사이클레이즈 활성 관련 질환의 예방 또는 치료용 약학적 조성물
  申请人：Medifron DBT Inc. (주) 메디프론디비티(120060469811) Corp. No ▼ 110111-1390816BRN ▼203-81-23576

  公开号：KR20200144180A

  公开（公告）日：2020-12-29

  본 발명은 N-치환된 티오우레아 또는 우레아 유도체 및 이를 유효성분으로 함유하는 글루타미닐 사이클레이즈(QC) 활성 관련 질환의 예방 또는 치료용 약학적 조성물에 관한 것이다. 본 발명에 따른 페닐티오우레아 유도체는 시험관 내(in vitro)에서 QC(glutaminyl cyclase)와 결합하여 50 nM 이하의 낮은 IC 값으로 QC를 저해하며, BBB(blood-brain barrier)를 통과하여 뇌 내부의 QC를 저해할 수 있고, 생체 내(in vivo)에서 뇌에서의 Aβ,Aβ, Aβ, 및Aβ의 농도를 현저하게 감소시킬 뿐만 아니라, 세포 독성이 없어 부작용의 우려가 적으므로, QC 활성 관련 질환인 알츠하이머병, 뇌혈관성 치매증, 두부 손상에 의한 치매, 다경색 치매, 알츠하이머병과 다경색 치매의 혼합형 또는 알코올성 치매 등을 포함하는 치매, 픽(pick)병, 크루츠-야콥(Creutzfeldt-Jakob)병, 두부손상에 의한 파킨슨(Parkinson)병, 헌팅턴(Huntington)병 등의 예방 또는 치료에 유용하게 사용될 수 있다.

  本发明涉及N-取代硫脲或脲衍生物，并含有其作为有效成分的谷氨酰胺环化酶（QC）活性相关疾病的预防或治疗药学组合物。根据本发明，苯硫脲衍生物在体外试管中与QC（谷氨酰胺环化酶）结合，以低于50 nM的IC值抑制QC，可以穿过血脑屏障到达大脑内部抑制QC，并且在体内可以显著降低大脑内Aβ、Aβ、Aβ和Aβ的浓度，并且由于没有细胞毒性，副作用较少，因此可用于QC活性相关疾病的预防或治疗，如阿尔茨海默病、脑血管性痴呆、脑损伤性痴呆、多发性梗塞性痴呆、阿尔茨海默病和多发性梗塞性痴呆的混合型或酒精性痴呆等痴呆症，Pick病，克罗伊茨菲尔特-雅各布病，脑损伤引起的帕金森病，亨廷顿病等的预防或治疗具有用处。
• Imino-Indeno[1,2-c] quinoline derivatives, their preparation processes, and pharmaceutical compositions comprising the same
  申请人：Tzeng Cherng-Chyi

  公开号：US20090111987A1

  公开（公告）日：2009-04-30

  Disclosed herein are novel imino-indeno[1,2-c]quinoline derivatives of formula (I): or a pharmaceutically acceptable salt or solvate thereof, wherein each of the substituents is given the definition as set forth in the Specification and Claims. Also disclosed are the preparation processes of these derivatives, their synthetic precursors and their uses in the manufacture of pharmaceutical compositions for use in the treatment of cancers.

  本文披露了一种新型的imino-indeno[1,2-c]quinoline衍生物，其化学式为(I)：或其药用可接受的盐或溶剂，其中每个取代基的定义如规范和权利要求所述。还披露了这些衍生物的制备过程、它们的合成前体以及它们在制造用于治疗癌症的药物组合物中的用途。
• Aminoquinoline Derived Heat Shock Protein 90 Inhibitors, Methods Of Preparing Same, And Methods For Their Use
  申请人：Sun Aiming

  公开号：US20110281908A1

  公开（公告）日：2011-11-17

  Novel classes of molecular chaperone Heat shock protein 90 (Hsp90) inhibitors and methods for making these classes are provided herein. These compounds are useful in treating and preventing cancer and other Hsp90-related diseases, such as inflammation and neurodegenerative disorders. Also provided herein are methods of treating and preventing cancer and other Hsp90 related disease. The methods include administering to a subject a therapeutically effective amount of an Hsp90 inhibitor.

  本文提供了新型分子伴侣热休克蛋白90（Hsp90）抑制剂的类别和制备方法。这些化合物可用于治疗和预防癌症和其他与Hsp90相关的疾病，如炎症和神经退行性疾病。本文还提供了治疗和预防癌症和其他Hsp90相关疾病的方法。该方法包括向患者施用治疗有效量的Hsp90抑制剂。