4'-[(2-butyl-1H-benzimidazol-1-yl)methyl]biphenyl-2-carboxylic acid | 133075-99-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4'-[(2-butyl-1H-benzimidazol-1-yl)methyl]biphenyl-2-carboxylic acid
• 英文别名: GR 109793；2-butyl-1-[(2'-carboxy-biphenyl-4-yl)methyl]benzimidazole；4'-[(2-n-butyl-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylic acid；2-[4-(2-Butylbenzimidazol-1-yl)methylphenyl]benzoic acid；2-[4-[(2-butylbenzimidazol-1-yl)methyl]phenyl]benzoic acid
• CAS: 133075-99-7
• 化学式: C₂₅H₂₄N₂O₂
• 分子量: 384.478
• InChiKey: TVNBFJNQCWCHHE-UHFFFAOYSA-N

物化性质

• 熔点：
  122-124 °C
• 沸点：
  603.9±48.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4'-[(2-butyl-1H-benzimidazol-1-yl)methyl]biphenyl-2-carboxylic acid 在 氯磺酸 作用下， 生成 4'-[(2-butyl-5-chlorosulfonyl-1H-benzimidazol-1-yl)methyl]biphenyl-2-carboxylic acid
  参考文献：
  名称：

  Design, synthesis, and evaluation of 5-sulfamoyl benzimidazole derivatives as novel angiotensin II receptor antagonists

  摘要：

  A series of 5-alkylsulfamoyl benzimidazole derivatives have been designed and synthesized as novel angiotensin II (Ang II) receptor antagonists. The compounds have been evaluated for in vitro Ang II antagonism and for in vivo antihypertensive activity on isolated rat aortic ring and desoxycortisone acetate induced hypertensive rats, respectively. The activity is found related to size of alkyl group. The maximum activity is observed with a compact and bulky alkyl group like tert-butyl and cyclohexyl. The compounds 4g and 4h have shown promising both in vitro and in vivo activities. A receptor binding model is also proposed on the basis on the basis of structure-activity relationship in this study. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.10.056
• 作为产物：
  描述：

  4-acetamidomethylbiphenyl-2'-carboxylic acid 在 potassium carbonate 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 xylene 为溶剂， 生成 4'-[(2-butyl-1H-benzimidazol-1-yl)methyl]biphenyl-2-carboxylic acid
  参考文献：
  名称：

  设计，合成和评估新型取代的苯并咪唑化合物作为血管紧张素II受体拮抗剂。

  摘要：

  已经设计，合成并评估了在2-位具有不同取代基的5-硝基苯并咪唑衍生物的血管紧张素II拮抗活性。已经提出了药物-受体相互作用模型。

  DOI：

  10.1016/j.bmcl.2005.05.054

文献信息

• Benzimidazole derivatives and their use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05128356A1

  公开（公告）日：1992-07-07

  Novel imidazole derivatives of the formula (I): ##STR1## wherein R.sup.1 is an optionally substituted alkyl group, R.sup.2 and R.sup.3 are independently a group capable of forming an anion or a group which can be changed thereinto, ring A is a benzene ring optionally having, besides the group shown by R.sup.2, further substituents, and X shows linkage of phenylene group and phenyl group directly or through a spacer whose atomic length is not more than 2 and a salt thereof, show antagonistic actions to angiotensin II, thus being useful as therapeutics for cardiovascular diseases.

  新型咪唑衍生物的公式（I）如下：##STR1##，其中R.sup.1是一个可选地取代的烷基团，R.sup.2和R.sup.3独立地是能够形成阴离子或可以转变为阴离子的基团，环A是一个苯环，除了R.sup.2所示的基团外，还可以有其他取代基，而X表示苯基团和苯基团直接连接或通过一个原子长度不超过2的间隔物连接，以及它们的盐，对血管紧张素II显示出拮抗作用，因此作为治疗心血管疾病的药物是有用的。
• Compound which is angiotensin II antagonist
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05243054A1

  公开（公告）日：1993-09-07

  ##STR1## compounds shown by the above formula or salt thereof show a strong angiotensin II antagonistic activity and hypotensive action and CNS activity, and are useful as therapeutic agents of circulatory diseases such as hypertensive diseases and heart diseases (e.g. hypercardia, heart failure, cardiac infarction), strokes, cerebral apoplexy, nephritis, atherosclerosis, Alzheimer's disease, senile dementia, etc.

  上述公式所示的##STR1##化合物或其盐表现出强烈的抗肾素II活性和降压作用以及中枢神经系统活性，并且可用作循环系统疾病（如高血压病和心脏病（例如高心排血量、心力衰竭、心肌梗死）、中风、脑卒中、肾炎、动脉粥样硬化、阿尔茨海默病、老年痴呆症等）的治疗剂。
• 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。
• Nonpeptide angiotensin II receptor antagonists. Synthesis and biological activity of benzimidazoles
  作者：Keiji Kubo、Yoshiyuki Inada、Yasuhisa Kohara、Yoshihiro Sugiura、Mami Ojima、Katsuhiko Itoh、Yoshiyasu Furukawa、Kohei Nishikawa、Takehiko Naka

  DOI：10.1021/jm00064a011

  日期：1993.6

  A series of substituted 2-butylbenzimidazoles bearing a biphenylylmethyl moiety at the 1-position was prepared via three synthetic routes and evaluated for angiotensin II (AII) receptor antagonistic activity (in vitro and in vivo). Binding affinity was determined using bovine adrenal cortical membrane. Substitution at the 4-, 5-, or 6-position reduced the affinity relative to that of the unsubstituted

  通过三种合成途径制备了一系列在1位带有一个联苯基甲基的取代的2-丁基苯并咪唑，并评估了其在体外和体内的血管紧张素II（AII）受体拮抗活性。使用牛肾上腺皮质膜测定结合亲和力。相对于未取代化合物（13a）的亲和力，在4-，5-或6-位的取代降低了亲和力。但是，大多数在7位带有取代基的化合物的结合亲和力与DuP 753（氯沙坦）相当。在功能研究中，发现羧基对于对抗AII的拮抗活性非常重要。2-丁基-1-[[[2'-（1H-四唑-5-基）联苯-4-基]甲基] -1H-苯并咪唑-4-，-5-，-6-的比较 AII诱导的兔主动脉环收缩试验中的-7和羧酸（15a-d）清楚地证明了羧基取代位置的重要性。在体内试验中，苯并咪唑-7-羧酸的口服给药对大鼠的AII诱导的升压反应产生了长期抑制作用。发现苯并咪唑环的7位上的最佳取代基是羧基或酯基。代表性化合物2-丁基-1-[[[2'-（1H-四唑-5-基）联苯-4-基]甲基]
• Benzimidazoles and medicaments containing these compounds
  申请人：Dr. Karl Thomae GmbH

  公开号：US05541229A1

  公开（公告）日：1996-07-30

  The invention relates to benzimidazoles of the formula ##STR1## in which R.sub.1 to R.sub.2 are as defined in claim 1, 1 and 3 isomer mixtures thereof and addition salts thereof which have valuable properties. In particular, the novel compounds are angiotensin II antagonists.

  该发明涉及公式##STR1##中的苯并咪唑，其中R.sub.1至R.sub.2如权利要求书中定义，1和3为其异构体混合物及其盐，具有有价值的性质。特别是，这些新化合物是血管紧张素II拮抗剂。