2-cyano(2,3-dihydrobenzo[b][1,4]dioxin-7-yl)-3-(3-(4-methyl-1H-imidazol-1-yl)propyl)guanidine | 1073243-19-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 2-cyano(2,3-dihydrobenzo[b][1,4]dioxin-7-yl)-3-(3-(4-methyl-1H-imidazol-1-yl)propyl)guanidine
• 英文别名: (3-(4-Methyl-1H-imidazol-1-yl)propyl)-2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-7-yl)guanidine；1-cyano-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[3-(4-methylimidazol-1-yl)propyl]guanidine
• CAS: 1073243-19-2
• 化学式: C₁₇H₂₀N₆O₂
• 分子量: 340.385
• InChiKey: AXZBOPMMEJHOFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  96.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(4-甲基咪唑-1-基)丙烷-1-胺 、 1-Cyano-3-(2,3-dihydro-1,4-benzodioxin-6-yl)thiourea 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以0.14 g的产率得到2-cyano(2,3-dihydrobenzo[b][1,4]dioxin-7-yl)-3-(3-(4-methyl-1H-imidazol-1-yl)propyl)guanidine
  参考文献：
  名称：

  Inhibitors for Human Glutaminyl Cyclase by Structure Based Design and Bioisosteric Replacement

  摘要：

  The inhibition of human glutaminyl cyclase (hQC) has come into focus as a new potential approach for the treatment of Alzheimer's disease. The hallmark of this principle is the prevention of the formation of A beta(3,11(pE)-40,42), as these A beta-species were shown to be of elevated neurotoxicity and likely to act as a seeding core leading to an accelerated formation of A beta-oligomers and fibrils. Starting from 1-(3-(1H-imidazol-1-yl)propyl)-3-(3,4-dimethoxyphenyl)thiourea, bioisosteric replacements led to the development of new classes of inhibitors. The optimization of the metal-binding group was achieved by homology modeling and afforded a first insight into the probable binding mode of the inhibitors in the hQC active site. The efficacy assessment of the hQC inhibitors was performed in cell culture, directly monitoring the inhibition of A beta(3,11(pE)-40,42) formation.

  DOI：

  10.1021/jm900969p

文献信息

• NOVEL INHIBITORS OF GLUTAMINYL CYCLASE
  申请人：Buchholz Mirko

  公开号：US20080267912A1

  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: A represents and B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Z are as defined throughout the description and the claims.

  化合物的公式（I），其组合物及用于疾病治疗的用途，或其药用盐、溶剂化合物或多晶体，包括其所有互变异构体和立体异构体，其中：A代表和B，R1，R2，R3，R4，R5，R6和Z如描述和索赔中定义的那样。
• CYANO-GUANIDINE DERIVATIVES AS GLUTAMINYL CYCLASE INHIBITORS
  申请人：Probiodrug AG

  公开号：EP2160380A1

  公开（公告）日：2010-03-10
• TREATING PATHOLOGICAL CONDITIONS BY DIRECT AND INDIRECT TARGETING OF SIRPA - CD47 INTERACTION
  申请人：Stichting Het Nederlands Kanker Instituut- Antoni van Leeuwenhoek Ziekenhuis

  公开号：EP3658141A1

  公开（公告）日：2020-06-03
• US8227498B2
  申请人：——

  公开号：US8227498B2

  公开（公告）日：2012-07-24
• [EN] CYANO-GUANIDINE DERIVATIVES AS GLUTAMINYL CYCLASE INHIBITORS<br/>[FR] DÉRIVÉS DE CYANO-GUANIDINE UTILISÉS COMME INHIBITEURS DE LA GLUTAMINYL CYCLASE
  申请人：PROBIODRUG AG

  公开号：WO2008128983A1

  公开（公告）日：2008-10-30

  [EN] The present invention relates to 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: A represents formula (A) or formula (B) and B, R¹, R², R³, R⁴, R⁵, R⁶ and Z are as defined throughout the description and the claims.
  [FR] La présente invention concerne des composés de formule (I), des combinaisons et utilisations desdits composés pour le traitement de maladies, ou un sel pharmaceutiquement acceptable, solvat ou polymorphe desdits composés, y compris tous leurs tautomères et stéréoisomères. Dans ladite formule, A représente la formule (A) ou la formule (B) et B, R¹, R², R³, R⁴, R⁵, R⁶ et Z sont tels que définis dans l'ensemble de la description et des revendications.