3-(5-methyl-1H-imidazol-1-yl)propan-1-amine | 279236-77-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(5-methyl-1H-imidazol-1-yl)propan-1-amine
• 英文别名: 3-(5-methylimidazol-1-yl)propan-1-amine
• CAS: 279236-77-0
• 化学式: C₇H₁₃N₃
• mdl: MFCD19203776
• 分子量: 139.2
• InChiKey: ORGYIMPJXDYEJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(5-methyl-1H-imidazol-1-yl)propan-1-amine 在 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 1-(3-(5-methyl-1H-imidazol-1-yl)propyl)-3-(quinolin-2-yl)thiourea
  参考文献：
  名称：

  Structure–activity relationship of human glutaminyl cyclase inhibitors having an N-(5-methyl-1H-imidazol-1-yl)propyl thiourea template

  摘要：

  In an effort to design inhibitors of human glutaminyl cyclase (QC), we have synthesized a library of N-aryl N-(5-methyl-1H-imidazol-1-yl)propyl thioureas and investigated the contribution of the aryl region of these compounds to their structure-activity relationships as cyclase inhibitors. Our design was guided by the proposed binding mode of the preferred substrate for the cyclase. In this series, compound 52 was identified as the most potent QC inhibitor with an IC50 value of 58 nM, which was two-fold more potent than the previously reported lead 2. Compound 52 is a most promising candidate for future evaluation to monitor its ability to reduce the formation of pGlu-A beta and A beta plaques in cells and transgenic animals. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.005
• 作为产物：
  描述：

  1-trityl-3-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-4-methyl-1H-imidazol-3-ium bromide 在 三氟乙酸 、 肼 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 3-(5-methyl-1H-imidazol-1-yl)propan-1-amine
  参考文献：
  名称：

  WO2008/128981

  摘要：

  公开号：

文献信息

• Discovery of Potent Human Glutaminyl Cyclase Inhibitors as Anti-Alzheimer’s Agents Based on Rational Design
  作者：Van-Hai Hoang、Phuong-Thao Tran、Minghua Cui、Van T. H. Ngo、Jihyae Ann、Jongmi Park、Jiyoun Lee、Kwanghyun Choi、Hanyang Cho、Hee Kim、Hee-Jin Ha、Hyun-Seok Hong、Sun Choi、Young-Ho Kim、Jeewoo Lee

  DOI：10.1021/acs.jmedchem.7b00098

  日期：2017.3.23

  proposed binding mode of the preferred substrate, Aβ3E−42. An in vitro structure–activity relationship study identified several excellent QC inhibitors demonstrating 5- to 40-fold increases in potency compared to a known QC inhibitor. When tested in mouse models of AD, compound 212 significantly reduced the brain concentrations of pyroform Aβ and total Aβ and restored cognitive functions. This potent Aβ-lowering

  谷氨酰胺基环化酶（QC）通过产生β淀粉样肽（pGlu-Aβ）的N末端焦谷氨酸与毒性淀粉样蛋白斑块的形成有关，因此可能参与了阿尔茨海默氏病（AD）的发病机理。我们基于优选底物Aβ3E-42的拟议结合模式设计了谷氨酰环化酶（QC）抑制剂库。一项体外结构-活性关系研究确定了几种出色的QC抑制剂，与已知的QC抑制剂相比，其效能提高了5至40倍。在AD的小鼠模型中测试时，化合物212显着降低了焦状Aβ和总Aβ的大脑浓度，并恢复了认知功能。这种强大的Aβ降低作用是通过将一个额外的结合区并入我们先前建立的药效团模型中而实现的，从而导致在QC结合位点与Glu327的羧酸酯基团发生强相互作用。我们的研究为设计新型QC抑制剂作为AD的潜在治疗方法提供了有用的见识。
• NOVEL INHIBITORS OF GLUTAMINYL CYCLASE
  申请人：Buchholz Mirko

  公开号：US20080267911A1

  公开（公告）日：2008-10-30

  Compounds of formula (I), combinations and uses thereof for disease therapy, or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof wherein: R 1 represents and R 2 , R 3 , R 4 , R 5 , R 6 , X 1 , X 2 , X 3 , X 4 , Y and Z are as defined throughout the description and the claims.

  式(I)的化合物，其组合物及用途用于疾病治疗，或其药学上可接受的盐、溶剂化合物或多晶形式，包括其所有互变异构体和立体异构体，其中： R1代表，而R2、R3、R4、R5、R6、X1、X2、X3、X4、Y和Z如描述和权利要求中所定义。
• 페닐티오우레아 유도체, 이의 제조방법 및 이를 유효성분으로 포함하는 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：KR20180062526A

  公开（公告）日：2018-06-11

  본 발명은 페닐티오우레아 유도체, 이의 제조방법 및 이를 유효성분으로 포함하는 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 감소시키고, 인지능력을 향상시키는 효과가 뛰어날 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.

  本发明涉及苯硫脲衍生物，其制备方法以及包含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物组合物。根据本发明，苯硫脲衍生物能够在体外与QC（谷氨酰胺环化酶）结合，以低于50 nM的IC值抑制QC，并且能够穿过血脑屏障，抑制大脑内的QC，在体内显著降低大脑中Aβ，Aβ，Aβ和Aβ的浓度，提高认知能力，而且由于没有细胞毒性，副作用较少，因此可用于预防或治疗与QC活性相关的疾病，如阿尔茨海默病，脑血管性痴呆症，因头部损伤导致的痴呆，多发性痴呆，阿尔茨海默病和多发性痴呆的混合型或酒精性痴呆等痴呆症，皮克病，克罗伊茨菲尔德-雅各布（Creutzfeldt-Jakob）病，因头部损伤导致的帕金森病，亨廷顿病等的预防或治疗。
• Structure-activity relationship investigation of Phe-Arg mimetic region of human glutaminyl cyclase inhibitors
  作者：Van T.H. Ngo、Van-Hai Hoang、Phuong-Thao Tran、Nguyen Van Manh、Jihyae Ann、Eunhye Kim、Minghua Cui、Sun Choi、Jiyoun Lee、Hee Kim、Hee-Jin Ha、Kwanghyun Choi、Young-Ho Kim、Jeewoo Lee

  DOI：10.1016/j.bmc.2018.04.040

  日期：2018.7

  AβN3pE-40-lowering effects in in vivo acute model with reasonable BBB penetration, without showing cytotoxicity and hERG inhibition. The molecular modeling analysis of 53 indicated that the salt bridge interaction and the hydrogen bonding in the active site provided a high potency. Given the potent activity and favorable BBB penetration with low cytotoxicity, we believe that compound 53 may serve as a

  谷氨酰环化酶（QC）由于其参与了阿尔茨海默氏病的发病机理，因此是有希望的治疗靶标。在这项研究中，我们开发了新型的QC抑制剂，其中包含3-氨基烷氧基-4-甲氧基苯基和4-氨基烷氧基苯基，以取代先前开发的药效团。鉴定了几种有效的抑制剂，显示出低纳摩尔范围的IC50值，并进一步研究了其体外毒性和体内活性。其中，抑制剂51和53在具有合理的BBB渗透的体内急性模型中显示出最有效的AβN3pE-40降低作用，而没有细胞毒性和hERG抑制作用。53的分子模型分析表明，活性位点中的盐桥相互作用和氢键提供了高效力。
• <i>In vitro</i>and<i>in silico</i>determination of glutaminyl cyclase inhibitors
  作者：Phuong-Thao Tran、Van-Hai Hoang、Jeewoo Lee、Tran Thi Thu Hien、Nguyen Thanh Tung、Son Tung Ngo

  DOI：10.1039/c9ra05763c

  日期：——

  Rational design of new hQC inhibitors.

  合理设计新的hQC抑制剂。