1-{[1,3-di(tert-butoxycarbonyl)imidazolidin-2-yl]imino}indazole | 1034875-05-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-{[1,3-di(tert-butoxycarbonyl)imidazolidin-2-yl]imino}indazole
• CAS: 1034875-05-2
• 化学式: C₂₀H₂₇N₅O₄
• 分子量: 401.465
• InChiKey: LSCVDWHEONDADK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.64
• 重原子数：
  29.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  89.26
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  1-{[1,3-di(tert-butoxycarbonyl)imidazolidin-2-yl]imino}indazole 在 三氟乙酸 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.0h， 以60%的产率得到Marsanidine
  参考文献：
  名称：

  [EN] DERIVATIVES OF 1-[(IMIDAZOLIDIN-2-YL)IMINO)]INDAZOLE
  [FR] DÉRIVÉS DU 1-[(IMIDAZOLIDIN-2-YL)IMINO)]INDAZOLE

  摘要：

  本发明提供了一种式子为(I)的化合物，其中R1表示氢、甲基或苯基；R2、R3、R4和R5表示氢、卤素，优选为氯原子，烷基，优选为甲基，烷氧基，优选为甲氧基；m表示数字0或1；HX表示硫酸、磷酸、醋酸、马龙酸、富马酸、草酸、乳酸、酒石酸、柠檬酸、葡萄糖酸、对甲苯磺酸、甲磺酸、氢溴酸或氢碘酸，优选为氢氯酸。本发明还提供将该化合物用作α2肾上腺素受体激动剂的方法。

  公开号：

  WO2009071906A1
• 作为产物：
  描述：

  6-溴吲唑 在 四(三苯基膦)钯 、 silver trifluoromethanesulfonate 、 Selectfluor 、 三乙胺 、 mercury dichloride 、 sodium hydroxide 、 hydroxylamine-O-sulfonic acid 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 26.16h， 生成 1-{[1,3-di(tert-butoxycarbonyl)imidazolidin-2-yl]imino}indazole 、 6-fluoro-1-{[1,3-di(tert-butoxycarbonyl)imidazolidin-2-yl]imino}-1H-indazole
  参考文献：
  名称：

  Fluorinated analogues of marsanidine, a highly α2-AR/imidazoline I1 binding site-selective hypotensive agent. Synthesis and biological activities

  摘要：

  The aim of these studies was to establish the influence of fluorination of the indazole ring on the pharmacological properties of two selective alpha(2)-aradrenoceptor (alpha(2)-AR) agonists: 1-[(imidazolidin-2-yl) imino]-1H-indazole (marsanidine, A) and its methylene analogue 1-[(4,5-dihydro-1H-imidazol-2-yl) methyl]-1H-indazole (B). Introduction of fluorine into the indazole ring of A and B reduced both binding affinity and alpha(2)-AR/I-1 imidazoline binding site selectivity. The most alpha(2)-AR-selective ligands were 6-fluoro-1-[(imidazolidin-2-yl)imino]-1H-indazole (6c) and 7-fluoro-1-[(imidazolidin-2-yl)imino]-1H-indazole (6d). The in vivo cardiovascular properties of fluorinated derivatives of A and B revealed that in both cases the C-7 fluorination leads to compounds with the highest hypotensive and bradycardic activities. The alpha(2)-AR partial agonist 6c was prepared as a potential lead compound for development of a radiotracer for PET imaging of brain alpha(2)-ARs. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.083

文献信息

• 1-[(Imidazolidin-2-yl)imino]indazole. Highly α₂/I₁ Selective Agonist: Synthesis, X-ray Structure, and Biological Activity
  作者：Franciszek Sa̧czewski、Anita Kornicka、Apolonia Rybczyńska、Alan L. Hudson、Shu Sean Miao、Maria Gdaniec、Konrad Boblewski、Artur Lehmann

  DOI：10.1021/jm800112s

  日期：2008.6.1

  Novel benzazole derivatives bearing a (imidazolidin-2-yl)imino moiety at position I or 2 were synthesized by reacting 1-amino- or 2-aminobenzazoles with N,N'-bis(tert-butoxycarbonyl)imidazolidine-2-thione in the presence of HgCl2. Structures of 1-[(imidazolidin-2-yl)imino]indazole (marsanidine, 13a) and free base of the 4-Cl derivative 12e were confirmed by X-ray single crystal structure analysis. Compound 13a was found to be the selective alpha(2)-adrenoceptor ligand with alpha(2)-adrenoceptor/imidazoline I-1 receptor selectivity ratio of 3879, while 1-[(imidazolidin-2-yl)imino]-7-methylindazole (13k) proved to be a mixed alpha(2)-adrenoceptor/imidazoline I-1 receptor agonist with alpha 2/I-1 selectivity ratio of 7.2. Compound 13k when administered intravenously to male Wistar rats induced a dose-dependent decrease in mean arterial blood pressure (ED50 = 0.6 mu g/kg) and heart rate, which was attenuated following pretreatment with alpha(2A)-adrenoceptor antagonist RX821002. Compound 13a may find a variety of medical uses ascribed to alpha(2)-adrenoceptor agonists, and its 7-methyl derivative 13k is a good candidate for development as a centrally acting antihypertensive drug.