5-[(trans-2,5)-5-aminomethyltetrahydrofuran-2-yl]imidazole

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-[(trans-2,5)-5-aminomethyltetrahydrofuran-2-yl]imidazole
• 英文别名: [(2S,5S)-5-(1H-imidazol-5-yl)oxolan-2-yl]methanamine
• 化学式: C₈H₁₃N₃O
• 分子量: 167.211
• InChiKey: KWWHIDCVULQSFZ-XPUUQOCRSA-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：

  5-[(trans-2,5)-5-aminomethyltetrahydrofuran-2-yl]imidazole 在 甲胺 作用下， 以 甲醇 为溶剂， 反应 21.0h， 生成 (+)-2-cyano-1-methyl-3-{(2S,5S)-2-[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：

  (5S)-5-[(benzyloxy)methyl]dihydrofuran-2(3H)-one 在 盐酸 、 palladium dihydroxide 、 正丁基锂 、 三丁基膦 、 diamide 、 四丁基氟化铵 、 二异丁基氢化铝 、 一水合肼 、 三苯基膦 、 环己烯 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 甲苯 、 苯 为溶剂， 反应 19.41h， 生成 5-[(trans-2,5)-5-aminomethyltetrahydrofuran-2-yl]imidazole
  参考文献：
  名称：

  通过Mitsunobu环化合成（+/-）-反式或顺式（5-氨基甲基四氢呋喃基）咪唑：对新型组胺H3或H4-配体的合成研究。

  摘要：

  通过Mitsunobu环化，从L-谷氨酸开始合成（+/-）-反式或顺式-4（5）-（5-氨基甲基四氢呋喃基）咪唑[1和2]。

  DOI：

  10.1248/cpb.51.325

文献信息

• Synthesis of 4(5)-[5-(Aminomethyl)tetrahydrofuran-2-yl- or 5-(Aminomethyl)-2,5-dihydrofuran-2-yl]imidazoles by Efficient Use of a PhSe Group:  Application to Novel Histamine H₃-Ligands¹
  作者：Shinya Harusawa、Tomonari Imazu、Seiichiroh Takashima、Lisa Araki、Hirofumi Ohishi、Takushi Kurihara、Yasuhiko Sakamoto、Yumiko Yamamoto、Atsushi Yamatodani

  DOI：10.1021/jo9910637

  日期：1999.11.1

  (+)-4(5)-[(2R,5S)-(5-Aminomethyl)tetrahydrofuran-2-yl]imidazole 1 and its C2' epimer (-)-2, which are the 5'-amino derivatives of a novel imidazole C-nucleoside, were synthesized via beta- and alpha-2'-phenylselenenyl nucleosides 15 and 16. The anomers 15 and 16 were provided by a new synthetic method for C-nucleosides via the elimination of PhSeCl and selenocyclization from diol intermediates 12 and 14, starting from L-glutamic acid. Their ent-1 and ent-2 (imifuramine), the latter of which was indicated as a novel type of histamine H-3-agonist confirmed by an in vivo brain microdialysis method, were synthesized by the same methodology from D-glutamic acid. The four isomers (3, 4, ent-3, and ent-4) of a 4(5)-[(5-aminomethyl)-2,5-dihydrofuran-2-yl]imidazole were also synthesized via the oxidative elimination of-the PhSe group of the key intermediates (15, 16, ent-15, and ent-16). In connection with this study, 4(5)-(5-aminomethylfuran-2-yl)-1H-imidazole (5) was also synthesized starting from D-ribose.

  将以下文本翻译成中文： (+)-4(5)-[(2R,5S)-(5-Aminomethyl)tetrahydrofuran-2-yl]imidazole 1 and its C2' epimer (-)-2, which are the 5'-amino derivatives of a novel imidazole C-nucleoside, were synthesized via beta- and alpha-2'-phenylselenenyl nucleosides 15 and 16. The anomers 15 and 16 were provided by a new synthetic method for C-nucleosides via the elimination of PhSeCl and selenocyclization from diol intermediates 12 and 14, starting from L-glutamic acid. Their ent-1 and ent-2 (imifuramine), the latter of which was indicated as a novel type of histamine H-3-agonist confirmed by an in vivo brain microdialysis method, were synthesized by the same methodology from D-glutamic acid. The four isomers (3, 4, ent-3, and ent-4) of a 4(5)-[(5-aminomethyl)-2,5-dihydrofuran-2-yl]imidazole were also synthesized via the oxidative elimination of the PhSe group of the key intermediates (15, 16, ent-15, and ent-16). In connection with this study, 4(5)-(5-aminomethylfuran-2-yl)-1H-imidazole (5) was also synthesized starting from D-ribose. --- (+)-4(5)-[(2R,5S)-(5-氨基甲基)四氢糠基-2-基]咪唑 1 与其 C2' 异构体 (-)-2，作为新型咪唑 C-核苷的 5'-氨基衍生物，通过 beta- 和 alpha-2'-苯基硒基核苷 15 和 16 合成。15 和 16 这种异构体通过一种新型 C-核苷合成方法制得，从 L-谷氨酸出发，通过二醇中间体 12 和 14 消除 PhSeCl 并进行硒环化反应。其 ent-1 和 ent-2（咪吗啡啉），其中后者被确认为一种新型组胺 H-3 �受体激动剂，通过体内脑微透析方法验证，也由此从 D-谷氨酸制得。此外，通过关键中间体（15、16、ent-15 和 ent-16）中 PhSe 基团的氧化消除，合成了 4(5)-[(5-氨基甲基)-2,5-二氢糠基-2-基]咪唑的四种异构体（3、4、ent-3 和 ent-4）。与本研究相关，4(5)-(5-氨基甲基糠基-2-基)-1H-咪唑 (5) 也从 D-核糖开始制得。
• Synthesis of (.+-.)-trans- or cis-(5-Aminomethyltetrahydrofuranyl)imidazole by Mitsunobu Cyclization: Synthetic Studies toward Novel Histamine H3 or H4-Ligands.
  作者：Shinya Harusawa、Lisa Araki、Tomonari Imazu、Hirofumi Ohishi、Yasuhiko Sakamoto、Takushi Kurihara

  DOI：10.1248/cpb.51.325

  日期：——

  The (+/-)-trans- or cis-4(5)-(5-aminomethyltetrahydrofuranyl)imidazole [1 and 2] were synthesized by the Mitsunobu cyclization, starting from L-glutamic acid.

  通过Mitsunobu环化，从L-谷氨酸开始合成（+/-）-反式或顺式-4（5）-（5-氨基甲基四氢呋喃基）咪唑[1和2]。
• 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.