(+)-4(5)-[(2R,5R)-(5-aminomethyl)tetrahydrofuran-2-yl]imidazole | 222419-33-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (+)-4(5)-[(2R,5R)-(5-aminomethyl)tetrahydrofuran-2-yl]imidazole
• 英文别名: (+)-4(5)-[(2R,5R)-5-aminomethyltetrahydrofuran-2-yl]imidazole；imifuramine；imifuramide；[(2R,5R)-5-(1H-imidazol-5-yl)oxolan-2-yl]methanamine
• CAS: 222419-33-2
• 化学式: C₈H₁₃N₃O
• 分子量: 167.211
• InChiKey: KWWHIDCVULQSFZ-HTRCEHHLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  63.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+)-4(5)-[(2R,5R)-(5-aminomethyl)tetrahydrofuran-2-yl]imidazole 在 甲胺 作用下， 以 甲醇 为溶剂， 生成 (-)-2-cyano-1-methyl-3-{(2R,5R)-5-[1H-imidazol-4(5)-yl]tetrahydrofuran-2-yl}methylguanidine
  参考文献：
  名称：

  A Selective Human H₄-Receptor Agonist:  (−)-2-Cyano-1-methyl-3-{(2R,5R)-5- [1H-imidazol-4(5)-yl]tetrahydrofuran-2-yl}methylguanidine

  摘要：

  A series of 16 compounds related to chiral 4(5)-(5-aminomethyltetrahydrofuran-2-yl)imidazoles (1) have been designed, synthesized, and examined in vitro by radioligand displacement studies and functional assays for both the human H-3- and H-4-receptors expressed in SK-N-MC cells. Among them, the (2S,5S)-isomer 1d of amino compounds showed approximately 300-fold higher selectivity at the H-3-receptor than the H-4-receptor. On the other hand, (2R,5S)- and (2R,5R)-cyanoguanidines 3b and 3c, in which the amino group of the compounds 1b and 1c was substituted by the cyanoguanidino moiety, bound to the H-4-receptor with a pEC(50) value of 6.65 and 7.11, respectively, and had >40-fold selectivities over the H3-receptor. As such, 3b and 3c are the first selective H-4 receptor agonists.

  DOI：

  10.1021/jm0300025
• 作为产物：
  描述：

  (-)-ethyl 4-[(2R,5R)-(5-hydroxymethyl)tetrahydrofuran-2-yl]imidazole-1-carboxylate 在 偶氮二甲酸二异丙酯 、 一水合肼 、 4-(二甲氨基)三苯基膦 作用下， 反应 6.0h， 生成 (+)-4(5)-[(2R,5R)-(5-aminomethyl)tetrahydrofuran-2-yl]imidazole
  参考文献：
  名称：

  Synthesis of imifuramine and its stereoisomers exhibiting histamine H3-agonistic activity

  摘要：

  The four possible stereoisomers of a novel imidazole C-nucleoside derivative were synthesized by the efficient use of a PhSe group. Among them, (+)-4(5)-[(2R,5R)-5-(aminomethyl)tetrahydrofuran-2-yl]imidazole (imifuramine) was indicated as a novel type of histamine H-3-agonist by a brain microdialysis method. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)00202-6

文献信息

• Efficient Synthesis of trans- or cis-4(5)-(5-Aminomethyltetrahydrofuran-2-yl)imidazoles via Diazafulvene Intermediates: Synthetic Approach toward Human Histamine H4-Ligands
  作者：Shinya Harusawa、Lisa Araki、Hirotaka Terashima、Makoto Kawamura、Seiichiro Takashima、Yasuhiko Sakamoto、Takeshi Hashimoto、Yumiko Yamamoto、Atsushi Yamatodani、Takushi Kurihara

  DOI：10.1248/cpb.51.832

  日期：——

  unsubstituted imidazole moiety in good yields. This methodology also afforded an alternative synthetic route to trans- and cis-ethyl 4(5)-(5-hydroxymethyltetrahydrofuran-2-yl)imidazole carboxylates (5 and 6), reported previously. Also, 4(5)-[(2R,5S)-5-aminomethyltetrahydrofuran-2-yl]imidazole (+)-2 was synthesized from ethyl 4(5)-(2-deoxy-beta-D-ribofuranosyl)imidazole-1-carboxylate (35) via the four steps involving

  预期（+）-4（5）-[（2R，5R）-5-氨基甲基四氢呋喃-2-基]咪唑[（+）-1，imifuramine]及其2R，5S-立体异构体（+）-2为碱化合物以开发选择性的人类组胺H4受体配体。（+）-1的改进合成是通过将Bu3P / N，N，N'，N'-四甲基偶氮二甲酰胺（TMAD）处理带有未取代咪唑部分的二醇17ab生成的二氮烯富烯中间体进行环化来完成的。这种方法还提供了另一种合成途径，可以合成先前报道的4（5）-（5-羟甲基四氢呋喃-2-基）咪唑羧酸酯的反式和顺式（5和6）。另外，由乙基4（5）-（2-脱氧-β-D-核呋喃呋喃糖基）咪唑-乙基合成了4（5）-[（（2R，5S）-5-氨基甲基四氢呋喃-2-基]咪唑（+）-2。通过涉及脱氧的四个步骤使1-羧酸盐（35）。
• Synthesis of imifuramine and its stereoisomers exhibiting histamine H3-agonistic activity
  作者：Shinya Harusawa、Tomonari Imazu、Seiichiroh Takashima、Lisa Araki、Hirofumi Ohishi、Takushi Kurihara、Yumiko Yamamoto、Atsushi Yamatodani

  DOI：10.1016/s0040-4039(99)00202-6

  日期：1999.3

  The four possible stereoisomers of a novel imidazole C-nucleoside derivative were synthesized by the efficient use of a PhSe group. Among them, (+)-4(5)-[(2R,5R)-5-(aminomethyl)tetrahydrofuran-2-yl]imidazole (imifuramine) was indicated as a novel type of histamine H-3-agonist by a brain microdialysis method. (C) 1999 Elsevier Science Ltd. All rights reserved.
• A Selective Human H₄-Receptor Agonist:  (−)-2-Cyano-1-methyl-3-{(2<i>R</i>,5<i>R</i>)-5- [1<i>H</i>-imidazol-4(5)-yl]tetrahydrofuran-2-yl}methylguanidine
  作者：Takeshi Hashimoto、Shinya Harusawa、Lisa Araki、Obbe P. Zuiderveld、Martine J. Smit、Tomonari Imazu、Seiichiroh Takashima、Yumiko Yamamoto、Yasuhiko Sakamoto、Takushi Kurihara、Rob Leurs、Remko A. Bakker、Atsushi Yamatodani

  DOI：10.1021/jm0300025

  日期：2003.7.1

  A series of 16 compounds related to chiral 4(5)-(5-aminomethyltetrahydrofuran-2-yl)imidazoles (1) have been designed, synthesized, and examined in vitro by radioligand displacement studies and functional assays for both the human H-3- and H-4-receptors expressed in SK-N-MC cells. Among them, the (2S,5S)-isomer 1d of amino compounds showed approximately 300-fold higher selectivity at the H-3-receptor than the H-4-receptor. On the other hand, (2R,5S)- and (2R,5R)-cyanoguanidines 3b and 3c, in which the amino group of the compounds 1b and 1c was substituted by the cyanoguanidino moiety, bound to the H-4-receptor with a pEC(50) value of 6.65 and 7.11, respectively, and had >40-fold selectivities over the H3-receptor. As such, 3b and 3c are the first selective H-4 receptor agonists.