1-(N,N-dimethylsulfamoyl)-2-(tert-butyldimethylsilyl)-5-(4-chlorobutyl)imidazole | 149647-72-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(N,N-dimethylsulfamoyl)-2-(tert-butyldimethylsilyl)-5-(4-chlorobutyl)imidazole
• 英文别名: 2-(tert-butyldimethylsilyl)-5-(4-chlorobutyl)-1-(dimethylsulfamoyl)imidazole；2-(t-Butyldimethylsilyl)-1-(dimethylsulfamoyl)-5-(4-chlorobutyl)imidazole；5-(4-chlorobutyl)-2-(tert-butyldimethylsilyl)-1-(N,N-dimethylsulfamoyl)-imidazole；2-(t-Butyldimethylsilyl)-5-(4-chlorobutyl)-1-(dimethylsulphamoyl)imidazole；2-[tert-butyl(dimethyl)silyl]-5-(4-chlorobutyl)-N,N-dimethylimidazole-1-sulfonamide
• CAS: 149647-72-3
• 化学式: C₁₅H₃₀ClN₃O₂SSi
• 分子量: 380.027
• InChiKey: YAWNGWBFVGBHBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.81
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  63.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(N,N-dimethylsulfamoyl)-2-(tert-butyldimethylsilyl)-5-(4-chlorobutyl)imidazole 在 盐酸 、 氨 作用下， 以 乙二醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 154.0h， 生成 2-[4-(3H-Imidazol-4-yl)-butyl]-5-phenyl-1H-imidazole
  参考文献：
  名称：

  Synthesis and biological assays of new H3-antagonists with imidazole and imidazoline polar groups

  摘要：

  New histamine H-3-receptor antagonists were synthesised and tested on rat brain membranes and on electrically stimulated guinea-pig ileum. The new compounds have a central polar group represented by a 2-alkylimidazole or a 2-thioimidazoline nucleus. The effect of the polar group basicity on the optimal length of the alkyl chain, connecting this group to a 4(5)-imidazolyl ring, was investigated. The best affinity values, obtained by displacement of [H-3]-RAMHA from rat brain, were obtained for the 2-alkylimidazole derivatives (2a-f) with tetramethylene chain (pK(i) 8.03-8.97), having an intermediate basicity between that of the previously reported 2-thioimidazoles (1a-i) and that of 2-alkylthioimidazolines (3a-h). In contrast, a general lowering of affinity (pK(i) 5.90-7.63) was observed for compounds of the last series (3a-h), with a complex dependence on the terminal lipophilic group and chain length. (C) 2000 Elsevier Science S.A. All rights reserved.

  DOI：

  10.1016/s0014-827x(99)00115-9
• 作为产物：
  描述：

  1-氯-4-碘丁烷 、 2-[二甲基(2-甲基-2-丙基)甲硅烷基]-N,N-二甲基-1H-咪唑-1-磺酰胺 在 正丁基锂 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 7.0h， 生成 1-(N,N-dimethylsulfamoyl)-2-(tert-butyldimethylsilyl)-5-(4-chlorobutyl)imidazole
  参考文献：
  名称：

  间取代的芳基（硫）醚作为组胺H3受体的有效部分激动剂（或拮抗剂），在侧链中缺少氮原子。

  摘要：

  合成了4-（3-芳氧基丙基）-1H-咪唑类化合物，该化合物在芳基环中具有间位取代基，并测试了其对组胺H（3）受体的活性。发现具有CN，Me或Br取代基的化合物是拮抗剂，而经过测试，CF（3），Et，i-Pr，t-Bu，COCH（3）或NO（2）取代基可显着提供部分激动剂在大鼠脑皮层突触小体上体外抑制[（3）H]组胺的释放。这些化合物在体内也具有活性，此外，CF（3）取代的化合物trifluproxim（UCL 1470，7）作为体内有效的全效激动剂，其ED（50）= 0.6 +/- 0.3 mg / kg每抑制小鼠脑N（tau）-甲基组胺形成。相关结构也已被研究。

  DOI：

  10.1021/jm031141p

文献信息

• Sulfonamides and sulfamides as H.sub.3 receptor antagonists
  申请人：James Black Foundation Limited

  公开号：US06080871A1

  公开（公告）日：2000-06-27

  Compounds of formula (I) or (II) wherein R.sup.1 is C.sub.4 to C.sub.20 hydrocarbyl (in which one or more hydrogen atoms may be replaced by halogen, and up to three carbon atoms may be replaced by oxygen, nitrogen or sulphur atoms, provided that R.sup.1 does not contain an --O--O-- group), R.sup.2 is H or C.sub.1 to C.sub.3 alkyl, m is from 1 to 15, n is from 2 to 6, each X group is independently (a), or one X group is --N(R.sup.4)--, --O-- or --S-- and the remaining X groups are independently (a), wherein R.sup.3 is H, C.sub.1 to C.sub.6 alkyl, --CO.sub.2 R.sup.5, --CONR.sup.5.sub.2, --CR.sup.5.sub.2 OR.sup.6 or --OR.sup.5 (in which R.sup.5 and R.sup.6 are H or C.sub.1 to C.sub.3 alkyl), and R.sup.4 is H or C.sub.1 to C.sub.6 alkyl, each Y group is independently --C(R.sup.3)R.sup.4 --, or up to two Y groups are --N(R.sup.4)--, --O-- or --S-- and the remaining Y groups are independently --C(R.sup.3)R.sup.4 --, wherein R.sup.3 is as defined above, one R.sup.4 group in the structure is imidazoyl or imidazoylalkyl and the remaining R.sup.4 groups are H or C.sub.1 to C.sub.6 alkyl, and Z is >C(R.sup.7)NR.sup.2 -- or >N--, wherein R.sup.7 is any of the groups recited above for R.sup.3, and pharmaceutically acceptable salts thereof are ligands at histamine H.sub.3 receptors. ##STR1##

  式(I)或(II)的化合物，其中R.sup.1为C.sub.4至C.sub.20的烃基（其中一个或多个氢原子可以被卤素取代，最多三个碳原子可以被氧、氮或硫原子取代，前提是R.sup.1不含有--O--O--基团），R.sup.2为H或C.sub.1至C.sub.3的烷基，m为1至15，n为2至6，每个X基团独立地为(a)，或一个X基团为--N(R.sup.4)--，--O--或--S--，其余的X基团独立地为(a)，其中R.sup.3为H，C.sub.1至C.sub.6的烷基，--CO.sub.2R.sup.5，--CONR.sup.5.sub.2，--CR.sup.5.sub.2OR.sup.6或--OR.sup.5（其中R.sup.5和R.sup.6为H或C.sub.1至C.sub.3的烷基），而R.sup.4为H或C.sub.1至C.sub.6的烷基，每个Y基团独立地为--C(R.sup.3)R.sup.4--，或最多两个Y基团为--N(R.sup.4)--，--O--或--S--，其余的Y基团独立地为--C(R.sup.3)R.sup.4--，其中R.sup.3如上定义，结构中的一个R.sup.4基团为咪唑基或咪唑基烷基，其余的R.sup.4基团为H或C.sub.1至C.sub.6的烷基，Z为>C(R.sup.7)NR.sup.2--或>N--，其中R.sup.7为R.sup.3中上述所述的任一基团，以及其药学上可接受的盐是组成组织胺H.sub.3受体的配体。
• A new convenient route for the synthesis of 4(5)-(ω-aminoalkyl)-1 H-imidazoles
  作者：Roeland C. Vollinga、Wiro M. P. B. Menge、Hendrik Timmerman

  DOI：10.1002/recl.19931120208

  日期：——

  A new route for the synthesis of 4(5)-(ω-aminoalkyl)-1 H-imidazoles 1 on a preparative scale through C5 lithiation of a 1,2-diprotected imidazole is described. When the described 1,2-diprotected 5-lithio-imidazole is treated with a 1-chloro-ω-iodoalkane 5, selective substitution of the iodo group takes place. The chloro group of the resultant 1.2-diprotected 5-(ω chloroalkyl)imidazole can be easily

  描述了通过1，2-二保护的咪唑的C5锂化以制备规模合成4（5）-（ω-氨基烷基）-1 H-咪唑1的新途径。当用1-氯-ω-碘代烷烃5处理所述的1，2-二保护的5-硫代咪唑时，碘基的选择性取代发生。所得的1.2-双保护的5-（ω氯烷基）咪唑的氯基可以容易地转化为氨基，但是显然也可以引入其他官能团。随后对5-取代的咪唑进行脱保护，以良好的总收率得到4（5）-（ω-氨基烷基）-1 H-咪唑1，作为多种组胺能化合物的前体。
• Imidazole derivatives as histamine receptor H3 (ANT) agonists
  申请人：Institut National de la Sante et de la Recherche Medical

  公开号：US06248765B1

  公开（公告）日：2001-06-19

  Novel imidazole derivatives as histamine receptor H3 antagonists and/or agonists, preparation thereof and therapeutical uses thereof. Chemical compounds for use as histamine receptor H3 agonists, partial agonists or antagonists, having general formula (Ia) or (Ib), the use thereof for making drugs, and methods for revealing the agonist, partial agonist or antagonist activity of such compounds in vivo, are disclosed.

  小说咪唑衍生物作为组胺受体H3的拮抗剂和/或激动剂，其制备方法和治疗用途。公开了用作组胺受体H3激动剂、部分激动剂或拮抗剂的化学化合物，其具有一般式（Ia）或（Ib），其用于制药，并公开了在体内揭示这些化合物的激动剂、部分激动剂或拮抗剂活性的方法。
• Meta-Substituted Aryl(thio)ethers as Potent Partial Agonists (or Antagonists) for the Histamine H₃ Receptor Lacking a Nitrogen Atom in the Side Chain
  作者：Nadia Pelloux-Léon、Abdellatif Fkyerat、Antonia Piripitsi、Wasyl Tertiuk、Walter Schunack、Holger Stark、Monique Garbarg、Xavier Ligneau、Jean-Michel Arrang、Jean-Charles Schwartz、C. Robin Ganellin

  DOI：10.1021/jm031141p

  日期：2004.6.1

  formation. Related structures have also been investigated; homologues 4-[4-(3-(trifluoromethyl)phenoxy)butyl]-1H-imidazole and 4-[2-(3-(trifluoromethyl)phenylthio)ethyl]-1H-imidazole are shown to be partial agonists, whereas the O isostere 4-[2-(3-(trifluoromethyl)phenoxy)ethyl]-1H-imidazole is an antagonist as is the S homologue 4-[3-(3-(trifluoromethyl)phenylthio)propyl]-1H-imidazole and its CH(2) isostere

  合成了4-（3-芳氧基丙基）-1H-咪唑类化合物，该化合物在芳基环中具有间位取代基，并测试了其对组胺H（3）受体的活性。发现具有CN，Me或Br取代基的化合物是拮抗剂，而经过测试，CF（3），Et，i-Pr，t-Bu，COCH（3）或NO（2）取代基可显着提供部分激动剂在大鼠脑皮层突触小体上体外抑制[（3）H]组胺的释放。这些化合物在体内也具有活性，此外，CF（3）取代的化合物trifluproxim（UCL 1470，7）作为体内有效的全效激动剂，其ED（50）= 0.6 +/- 0.3 mg / kg每抑制小鼠脑N（tau）-甲基组胺形成。相关结构也已被研究。
• Synthesis and biological assays of new H3-antagonists with imidazole and imidazoline polar groups
  作者：Marco Mor、Fabrizio Bordi、Claudia Silva、Silvia Rivara、Valentina Zuliani、Federica Vacondio、Giovanni Morini、Elisabetta Barocelli、Vigilio Ballabeni、Mariannina Impicciatore、Pier Vincenzo Plazzi

  DOI：10.1016/s0014-827x(99)00115-9

  日期：2000.1

  New histamine H-3-receptor antagonists were synthesised and tested on rat brain membranes and on electrically stimulated guinea-pig ileum. The new compounds have a central polar group represented by a 2-alkylimidazole or a 2-thioimidazoline nucleus. The effect of the polar group basicity on the optimal length of the alkyl chain, connecting this group to a 4(5)-imidazolyl ring, was investigated. The best affinity values, obtained by displacement of [H-3]-RAMHA from rat brain, were obtained for the 2-alkylimidazole derivatives (2a-f) with tetramethylene chain (pK(i) 8.03-8.97), having an intermediate basicity between that of the previously reported 2-thioimidazoles (1a-i) and that of 2-alkylthioimidazolines (3a-h). In contrast, a general lowering of affinity (pK(i) 5.90-7.63) was observed for compounds of the last series (3a-h), with a complex dependence on the terminal lipophilic group and chain length. (C) 2000 Elsevier Science S.A. All rights reserved.