2-butyl-5-nitrobenzimidazole | 28742-67-8

• 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: 2-butyl-5-nitrobenzimidazole
• 英文别名: 2-butyl-6-nitro-1H-benzimidazole
• CAS: 28742-67-8
• 化学式: C₁₁H₁₃N₃O₂
• mdl: MFCD27948808
• 分子量: 219.243
• InChiKey: FRLKLXRCNYGIOL-UHFFFAOYSA-N

物化性质

• 熔点：
  134-135 °C(Solv: methanol (67-56-1); water (7732-18-5))
• 沸点：
  445.8±18.0 °C(Predicted)
• 密度：
  1.268±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  74.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-butyl-5-nitrobenzimidazole 在 盐酸 、 sodium azide 、 potassium carbonate 、 氯化铵 、 tin(ll) chloride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 97.0h， 生成 N-[2-butyl-1-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazol-5-yl]ethanimine
  参考文献：
  名称：

  一些新的取代苯并咪唑的合理设计，合成，表征和降压活性

  摘要：

  设计，合成了一系列5-取代的苯并咪唑，并通过豚鼠的急性肾高压评估了体内的降压活性。与标准药物（氯沙坦）相比，该系列的所有化合物均具有显着的活性。发现该活性在苯并咪唑的5-位上的取代烷基氨基中相对较好。用四种化合物DR-13，DR-14，DR-15和DR-16观察到了与氯沙坦几乎等效的最大活性。

  DOI：

  10.1007/s00044-012-0462-7
• 作为产物：
  描述：

  4-硝基邻苯二胺 在 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 生成 2-butyl-5-nitrobenzimidazole
  参考文献：
  名称：

  Design, synthesis and biological evaluation of new 5-nitro benzimidazole derivatives as AT1 antagonists with anti-hypertension activities

  摘要：

  The design, synthesis, in vitro and in vivo evaluation of 5-nitro benzimidazole with 1,4-disubsituted or 1,5-disubsituted indole derivatives as novel angiotensin II receptor antagonist is outlined. Radioligand binding assays showed that 2-(4-((2-butyl-5-nitro-1H-benzo[d] imidazol-1-yl) methyl)-1H-indol-1-yl) benzoic acid, compound 3, displayed a high affinity for the angiotensin II type 1 receptor with IC50 value of 1.03 +/- 0.26 nM. The biological evaluation on spontaneously hypertensive rats and renal hypertensive rats showed that 3 could cause significant decrease on MBP in a dose dependent manner, whose maximal response lowered 30 mmHg of MBP at 5 mg/kg and 41 mmHg of MBP at 10 mg/kg after oral administration, and the significant antihypertensive effect lasted beyond 24 h, which is better than Losartan. Taken together 3 could be considered as an effective and durable anti-hypertension drug candidate. These encouraging results are deserved of further investigation towards its use for therapeutic benefit. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.02.008

文献信息

• Expeditious and Efficient Synthesis of Benzoxazoles, Benzothiazoles, Benzimidazoles Catalyzed by Ga(OTf)3 under Solvent-Free Conditions
  作者：Juyan Liu、Qian Liu、Wei Xu、Weilu Wang

  DOI：10.1002/cjoc.201180310

  日期：2011.8

  new and efficient method for the synthesis of benzoxazoles, benzothiazoles, benzimidazoles from reactions of o‐substituted aminoaromatics with orthoesters in the presence of catalytic amounts of Ga(OTf)3 under solvent‐free conditions is presented. The remarkable features of this new protocol are high conversion, very short reaction times, cleaner reaction profiles under solvent‐free conditions, straight

  提出了在无溶剂条件下，在催化量的Ga（OTf）3存在下，由邻位取代的氨基芳烃与原酸酯反应合成苯并恶唑，苯并噻唑，苯并咪唑的新方法。该新方案的显着特征是高转化率，非常短的反应时间，在无溶剂条件下更干净的反应曲线，直接的程序以及使用相对无毒的催化剂。
• Synthesis of 2-substituted benzimidazoles by iodine-mediated condensation of orthoesters with 1,2-phenylenediamines
  作者：Zhan-Hui Zhang、Jian-Jiong Li、Yuan-Zhe Gao、Yu-Heng Liu

  DOI：10.1002/jhet.5570440642

  日期：2007.11

  Iodine was found to be an efficient catalyst for the synthesis of 2-substituted benzimidazoles by the condensation of orthoesters and 1,2-phenylenediamines in good to excellent yields under mild reaction conditions.

  发现碘是在温和的反应条件下，通过原酸酯和1,2-苯二胺的缩合反应，可以高效合成2-取代的苯并咪唑的有效催化剂。
• 6-Substituted benzimidazoles as new nonpeptide angiotensin II receptor antagonists: synthesis, biological activity, and structure-activity relationships
  作者：Uwe J. Ries、Gerhard Mihm、Berthold Narr、Kai M. Hasselbach、Helmut Wittneben、Michael Entzeroth、Jacobus C. A. van Meel、Wolfgang Wienen、Norbert H. Hauel

  DOI：10.1021/jm00077a007

  日期：1993.12

  reported nonpeptidic angiotensin II (AII) receptor antagonists DuP753 (1) and Exp 7711 (2), we have designed and investigated novel substituted benzimidazoles. Systemic variation of several substituents at the benzimidazole ring positions 4-7 led to the finding that substitution in position 6 with acylamino groups results in highly active AII antagonists. Compounds with 6-membered lactam or sultam substituents

  从最近报道的非肽类血管紧张素II（AII）受体拮抗剂DuP753（1）和Exp 7711（2）开始，我们设计并研究了新型取代的苯并咪唑。苯并咪唑环位置4-7上几个取代基的系统变化导致发现，位置6被酰基氨基取代会产生高活性的AII拮抗剂。在苯并咪唑的6位上具有6元内酰胺或sultam取代基的化合物在低纳摩尔范围内显示受体活性，但当口服给予大鼠时仅具有弱活性。相反，用碱性杂环类似地取代苯并咪唑部分产生有效的AII拮抗剂，其在口服后也被很好地吸收。该系列中活性最高的化合物33（BIBR 277），被选为临床发展的候选人。在分子模型研究的基础上，提出了这种新型的AII拮抗剂与AT1受体的结合模型。
• Synthesis and biological evaluation of 4′-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives as dual angiotensin II/endothelin A receptor antagonists
  作者：Renren Bai、Zhen Wei、Jie Liu、Weijia Xie、Hequan Yao、Xiaoming Wu、Jieyun Jiang、Qiujuan Wang、Jinyi Xu

  DOI：10.1016/j.bmc.2012.06.011

  日期：2012.8

  A series of 4′-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives (Ia–Il) were synthesized and biologically evaluated. It was found that Ig, the most active compound, antagonized both Ang II AT1 and endothelin ETA receptors (AT1 IC50 = 8.5, ETA IC50 = 8.9 nM), and was more potent than losartan in RHRs with no significant effect on heart rate. The preliminary structure–activity relationships

  合成了一系列4'-[[（苯并咪唑-1-基）甲基]联苯-2-磺酰胺衍生物（Ia-11），并对其进行了生物学评估。发现最活跃的化合物Ig拮抗Ang II AT 1和内皮素ET A受体（AT 1 IC 50  = 8.5，ET A IC 50  = 8.9 nM），并且在RHRs中比氯沙坦更有效，没有显着性对心率的影响。初步的结构-活性关系也在本文中进行了讨论。
• Baker’s Yeast-Mediated Regioselective Reduction of 2,4-Dinitroacylanilines: Synthesis of 2-Substituted 6-Nitrobenzimidazoles
  作者：Arturo Navarro-Ocaña、Luís F. Olguín、Manuel Jiménez-Estrada、Eduardo Bárzana

  DOI：10.1055/s-2004-837203

  日期：——

  Several 2,4-dinitro-N-acylanilines were regioselectively reduced at the C-2 position by baker's yeast in slightly basic media (pH = 7.5) to afford 2-amino-4-nitroacylanilines, which were then cyclized under acidic conditions to the corresponding 2-substituted-6-nitrobenzimidazoles. The benzimidazoles thus obtained can be employed as precursors for bioactive derivatives.

  几种 2,4-二硝基-N-酰基苯胺在微碱性介质（pH = 7.5）中被面包酵母在 C-2 位置区域选择性还原，得到 2-氨基-4-硝基酰基苯胺，然后在酸性条件下环化为相应的 2-取代-6-硝基苯并咪唑。由此获得的苯并咪唑可用作生物活性衍生物的前体。