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-(2-pyridynylmethyl)benzamide | 189268-93-7

• 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-(2-pyridynylmethyl)benzamide
• 英文别名: 1-(3-tert-Butyldiphenylsilyloxymethyl-2,4-dichlorophenyl)-2-[4-[N-(pyridin-2-ylmethyl)carbamoyl]-cinnamoylaminomethyl]pyrrole；1-(3-tert-Butyldiphenylsilyloxymethyl-2,4-dichlorophenyl)-2-[4-[N-(2-pyridylmethyl)carbamoyl]-cinnamoylaminomethyl]pyrrole；4-[(E)-3-[[1-[3-[[tert-butyl(diphenyl)silyl]oxymethyl]-2,4-dichlorophenyl]pyrrol-2-yl]methylamino]-3-oxoprop-1-enyl]-N-(pyridin-2-ylmethyl)benzamide
• CAS: 189268-93-7
• 化学式: C₄₄H₄₂Cl₂N₄O₃Si
• 分子量: 773.834
• InChiKey: MHUHOQXUYWOQHO-YYADALCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.52
• 重原子数：
  54
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  4

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-(2-pyridynylmethyl)benzamide 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-[(pyridin-2-ylmethyl)-carbamoyl]-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：

  (E)-4-(3-甲氧基-3-氧代丙-1-烯-1-基)苯甲酸 在 sodium hydroxide 、 1-(3-dimethylaminopropyl)-3-ethoxycarbodiimide hydrochloride 、 1-羟基苯并三唑 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 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-(2-pyridynylmethyl)benzamide
  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。
• Quinoline derivatives as bradykinin agonists
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US06015818A1

  公开（公告）日：2000-01-18

  This invention relates to a compound of formula (1) wherein R.sup.1 is halogen, etc., R.sup.2 is halogen, etc., R.sup.3 is amino substituted with substituent(s) selected from the group consisting of lower alkyl and acyl, etc., R.sup.4 is heterocyclic (lower)alkyl, R.sup.5 is lower alkyl, and A.sup.1 is lower alkylene, 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 hypertension or the like. ##STR1##

  这项发明涉及一种化合物，其化学式为（1），其中R.sup.1是卤素等，R.sup.2是卤素等，R.sup.3是氨基，带有从羧甲基和酰基等组成的取代基，R.sup.4是杂环（较低）烷基，R.sup.5是较低烷基，A.sup.1是较低亚烯，并且其药学上可接受的盐，以及制备该化合物的方法，包括具有相同化合物的药物组合物，以及在预防和/或治疗高血压或类似疾病中的治疗方法。
• 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.