4-{(1E)-3-[({1-[3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2,4-dichlorophenyl]-1H-pyrrol-2-yl}methyl)amino]-3-oxo-1-propenyl}-N,N-dimethylbenzamide | 189268-90-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 4-{(1E)-3-[({1-[3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2,4-dichlorophenyl]-1H-pyrrol-2-yl}methyl)amino]-3-oxo-1-propenyl}-N,N-dimethylbenzamide
• 英文别名: 1-(3-tert-Butyldiphenylsilyloxymethyl-2,4-dichlorophenyl)-2-[4-(dimethylcarbamoyl)cinnamoylaminomethyl]pyrrole；4-[(E)-3-[[1-[3-[[tert-butyl(diphenyl)silyl]oxymethyl]-2,4-dichlorophenyl]pyrrol-2-yl]methylamino]-3-oxoprop-1-enyl]-N,N-dimethylbenzamide
• CAS: 189268-90-4
• 化学式: C₄₀H₄₁Cl₂N₃O₃Si
• 分子量: 710.775
• InChiKey: RWTIPASANZNSNM-LKUDQCMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.89
• 重原子数：
  49
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-{(1E)-3-[({1-[3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2,4-dichlorophenyl]-1H-pyrrol-2-yl}methyl)amino]-3-oxo-1-propenyl}-N,N-dimethylbenzamide 在 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.5h， 生成 Methanesulfonic acid 2,6-dichloro-3-(2-{[(E)-3-(4-dimethylcarbamoyl-phenyl)-acryloylamino]-methyl}-pyrrol-1-yl)-benzyl ester
  参考文献：
  名称：

  A New Series of Highly Potent Non-Peptide Bradykinin B₂ Receptor Antagonists Incorporating the 4-Heteroarylquinoline Framework. Improvement of Aqueous Solubility and New Insights into Species Difference

  摘要：

  Introduction of nitrogen-containing heteroaromatic groups at the 4-position of the quinoline moiety of our non-peptide B-2 receptor antagonists resulted in enhancing binding affinities for the human B-2 receptor and reducing binding affinities for the guinea pig one, providing new structural insights into species difference. A CoMFA study focused on the diversity of the quinoline moiety afforded correlative and predictive QSAR models of binding for the human B-2 receptor but not for the guinea pig one. A series of 4-(I-imidazolyl)quinoline derivatives could be dissolved in a 5% aqueous solution of citric acid up to a concentration of 10 mg/mL. A representative compound 48a inhibited the specific binding of [H-3]BK to the cloned human B-2 receptor expressed in Chinese hamster ovary cells with an IC50 value of 0.26 nM and significantly inhibited BK-induced bronchoconstriction in guinea pigs even at 1 mug/kg by intravenous administration.

  DOI：

  10.1021/jm030159x
• 作为产物：
  描述：

  3-((tert-butyldiphenylsilyloxy)methyl)-2,4-dichloroaniline 在 lithium aluminium tetrahydride 、 1-(3-dimethylaminopropyl)-3-ethoxycarbodiimide hydrochloride 、 1-羟基苯并三唑 作用下， 以 四氢呋喃 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 4-{(1E)-3-[({1-[3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2,4-dichlorophenyl]-1H-pyrrol-2-yl}methyl)amino]-3-oxo-1-propenyl}-N,N-dimethylbenzamide
  参考文献：
  名称：

  A New Series of Highly Potent Non-Peptide Bradykinin B₂ Receptor Antagonists Incorporating the 4-Heteroarylquinoline Framework. Improvement of Aqueous Solubility and New Insights into Species Difference

  摘要：

  Introduction of nitrogen-containing heteroaromatic groups at the 4-position of the quinoline moiety of our non-peptide B-2 receptor antagonists resulted in enhancing binding affinities for the human B-2 receptor and reducing binding affinities for the guinea pig one, providing new structural insights into species difference. A CoMFA study focused on the diversity of the quinoline moiety afforded correlative and predictive QSAR models of binding for the human B-2 receptor but not for the guinea pig one. A series of 4-(I-imidazolyl)quinoline derivatives could be dissolved in a 5% aqueous solution of citric acid up to a concentration of 10 mg/mL. A representative compound 48a inhibited the specific binding of [H-3]BK to the cloned human B-2 receptor expressed in Chinese hamster ovary cells with an IC50 value of 0.26 nM and significantly inhibited BK-induced bronchoconstriction in guinea pigs even at 1 mug/kg by intravenous administration.

  DOI：

  10.1021/jm030159x

文献信息

• Heterocyclic compounds as bradykinin antagonists
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US06008229A1

  公开（公告）日：1999-12-28

  This invention relates to a compound of formula (I) wherein A.sup.1 is lower alkylene, R.sup.1 is substituted quinolyl, etc., R.sup.2 is hydrogen, halogen or lower alkyl, R.sup.3 is halogen or lower alkyl, and R.sup.4 is a group of the formula: -Q-A.sup.2 -R.sup.5, etc., in which R.sup.5 is amino, acylamino, etc., A.sup.2 is lower alkylene or a single bond, and Q is a group of formula (a), and pharmaceutically acceptable salts thereof, to processes for preparation thereof, to a pharmaceutical composition comprising the same, and to methods of using the same therapeutically in the prevention and/or the treatment of bradykinin or its analogues mediated diseases in human being or animals. ##STR1##

  本发明涉及一种化合物，其化学式为（I），其中A.sup.1为较低的烷基，R.sup.1为取代的喹啉基，R.sup.2为氢、卤素或较低的烷基，R.sup.3为卤素或较低的烷基，R.sup.4为下列结构的基团：-Q-A.sup.2-R.sup.5等，其中R.sup.5为氨基、酰胺基等，A.sup.2为较低的烷基或单键，Q为化学式（a）的基团，以及其药学上可接受的盐，其制备方法，包含该化合物的药物组合物，以及在人类或动物中预防和/或治疗由激肽酶或其类似物介导的疾病中的治疗方法。
• A New Series of Highly Potent Non-Peptide Bradykinin B₂ Receptor Antagonists Incorporating the 4-Heteroarylquinoline Framework. Improvement of Aqueous Solubility and New Insights into Species Difference
  作者：Yuki Sawada、Hiroshi Kayakiri、Yoshito Abe、Keisuke Imai、Tsuyoshi Mizutani、Noriaki Inamura、Masayuki Asano、Ichiro Aramori、Chie Hatori、Akira Katayama、Teruo Oku、Hirokazu Tanaka

  DOI：10.1021/jm030159x

  日期：2004.3.1

  Introduction of nitrogen-containing heteroaromatic groups at the 4-position of the quinoline moiety of our non-peptide B-2 receptor antagonists resulted in enhancing binding affinities for the human B-2 receptor and reducing binding affinities for the guinea pig one, providing new structural insights into species difference. A CoMFA study focused on the diversity of the quinoline moiety afforded correlative and predictive QSAR models of binding for the human B-2 receptor but not for the guinea pig one. A series of 4-(I-imidazolyl)quinoline derivatives could be dissolved in a 5% aqueous solution of citric acid up to a concentration of 10 mg/mL. A representative compound 48a inhibited the specific binding of [H-3]BK to the cloned human B-2 receptor expressed in Chinese hamster ovary cells with an IC50 value of 0.26 nM and significantly inhibited BK-induced bronchoconstriction in guinea pigs even at 1 mug/kg by intravenous administration.