4-(1H-咪唑-1-基)-2-甲基-8-羟基喹啉 | 54666-28-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 4-(1H-咪唑-1-基)-2-甲基-8-羟基喹啉
• 英文名称: 4-(1H-imidazol-1-yl)-2-methyl-8-quinolinol
• 英文别名: 2-Methyl-4-(1-imidazolyl)-8-hydroxychinolin；8-hydroxy-4-[1H-imidazol-1-yl]-2-methylquinoline；4-imidazol-1-yl-2-methyl-quinolin-8-ol；8-hydroxy-4-(imidazol-1-yl)-2-methylquinoline；8-Hydroxy-4-(1H-imidazol-yl)-2-methylquinoline；4-imidazol-1-yl-2-methylquinolin-8-ol
• CAS: 54666-28-3
• 化学式: C₁₃H₁₁N₃O
• 分子量: 225.25
• InChiKey: SOJUHQVMWVAPJB-UHFFFAOYSA-N

物化性质

• 熔点：
  192-196 °C(Solv: ethyl ether (60-29-7))
• 沸点：
  477.3±45.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  50.9
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-(1H-咪唑-1-基)-2-甲基-8-羟基喹啉 在 4 A molecular sieve 、 四丁基碘化铵 、 potassium carbonate 、 一水合肼 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 3-{[({2-[2,4-dichloro-3-({[4-(1H-imidazol-1-yl)-2-methyl-8-quinolinyl]oxy}methyl)methylanilino]-2-oxoethyl}amino)carbonyl]amino}-N-(4-pyridinyl)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
• 作为产物：
  描述：

  4-羟基-8-甲氧基-2-甲基喹啉 在 三溴化硼 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 10.0h， 生成 4-(1H-咪唑-1-基)-2-甲基-8-羟基喹啉
  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

• Quinoline derivatives, processes for their preparation and their use as
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US06083959A1

  公开（公告）日：2000-07-04

  A compound of the formula: ##STR1## wherein R.sup.1 is lower alkyl, R.sup.2 is hydrogen, lower alkyl or a heterocyclic group, R.sup.3 is hydrogen, lower alkyl or halogen, R.sup.4 is lower alkyl or halogen, R.sup.5 is nitro or amino substituted with substituent(s) selected from the group consisting of lower alkyl and acyl, and A is lower alkylene.

  一种化合物的化学式：##STR1## 其中 R.sup.1 是较低的烷基，R.sup.2 是氢、较低烷基或杂环基，R.sup.3 是氢、较低烷基或卤素，R.sup.4 是较低烷基或卤素，R.sup.5 是硝基或氨基，带有从较低烷基和酰基的取代基选取的取代基，A 是较低的亚烯基。
• Heterocyclic compounds as bradykinin antagonists
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US06344462B1

  公开（公告）日：2002-02-05

  This invention relates to a compound of the formula: wherein A1 is lower alkylene, R1 is substituted quinolyl, etc., R2 is hydrogen, halogen or lower alkyl, R3 is halogen or lower alkyl, and R4 is a group of the formula: —Q—A2—R5, etc.,  in which R5 is amino, acylamino, etc., A2 is lower alkylene or a single bond, and Q is a group of the formula:  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.

  这项发明涉及一种化合物，其化学式为：其中A1是较低的烷基烯，R1是取代的喹啉基等，R2是氢、卤素或较低的烷基，R3是卤素或较低的烷基，R4是式的一个基团：—Q—A2—R5等，其中R5是氨基、酰胺基等，A2是较低的烷基烯或一个单键，Q是式的一个基团：，以及其在药学上可接受的盐，制备方法，包含相同化合物的药物组成，以及在治疗人类或动物的布雷金激肽或其类似物介导的疾病的预防和/或治疗中使用的方法。
• Heterocyclic benzenesulphonamide compounds as bradykinine antagonists
  申请人：Fournier Industrie et Sante

  公开号：US06479515B1

  公开（公告）日：2002-11-12

  The invention concerns compounds selected among the group consisting of (i) compounds of formula (I) wherein: Het1 represents a nitrogenous heterocycle with 5 apices, in particular imidazole, pyrazole, or triazole; Het2 represents a nitrogenous heterocycle with 4, 5 or 6 apices, selected among the heterocycles: (II) wherein R1 and R2 are defined as mentioned in the description; and (ii) their additive salts. The invention also concerns the method for preparing said compounds and their use in therapy, in particular for treating pathologies involving bradykinine.

  这项发明涉及选自以下组合的化合物：(i) 公式(I)中的化合物，其中：Het1代表具有5个顶点的氮杂环，特别是咪唑、吡唑或三唑；Het2代表具有4、5或6个顶点的氮杂环，选自以下杂环：(II)，其中R1和R2如描述中所述定义；以及(ii) 它们的加合盐。该发明还涉及制备所述化合物的方法以及它们在治疗中的用途，特别是用于治疗涉及激肽酶的病理问题。
• [EN] HETEROCYCLIC COMPOUNDS AS BRADYKININ ANTAGONISTS<br/>[FR] COMPOSES HETEROCYCLIQUES UTILISES COMME ANTAGONISTES DE LA BRADYKININE
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：WO1997011069A1

  公开（公告）日：1997-03-27

  (EN) This invention relates to a compound of formula (I) wherein A1 is lower alkylene, R1 is substituted quinolyl, etc., R2 is hydrogen, halogen or lower alkyl, R3 is halogen or lower alkyl, and R4 is a group of the formula: -Q-A2-R5, etc., in which R5 is amino, acylamino, etc., A2 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.(FR) Cette invention se rapporte à un composé représenté par la formule (I), où A1 représente alkylène inférieur, R1 représente quinolyle substitué, etc., R2 représente hydrogène, halogène ou alkyle inférieur, R3 représente halogène ou alkyle inférieur, et R4 représente un groupe de la formule: -Q-A2-R5, etc., où R5 représente amino, acylamino, etc., A2 représente alkylène inférieur ou une liaison simple, et Q représente un groupe de la formule (a), etc., ainsi qu'à des sels d'un tel composé, acceptables sur le plan pharmaceutique, à des procédés pour le préparer, à une composition pharmaceutique le contenant, ainsi qu'à des procédés d'utilisation thérapeutique d'un tel composé dans la prévention et/ou le traitement des maladies à médiation par la bradykinine ou ses analogues, chez l'homme ou chez des animaux.

  该发明涉及一种化合物，其化学式为(I)，其中A1为低级烷基，R1为取代的喹啉基等，R2为氢、卤素或低级烷基，R3为卤素或低级烷基，R4为以下式的基团：-Q-A2-R5等，其中R5为氨基、酰胺基等，A2为低级烷基或单键，Q为以下式的基团(a)，以及其药学上可接受的盐，制备该化合物的方法，包含该化合物的药物组合物，以及在预防和/或治疗人类或动物中由激肽酶介导的激肽或其类似物引起的疾病中治疗其的方法。
• 8-OXY-QUINOLINE DERIVATIVES AS BRADYKININ B2 RECEPTOR MODULATORS
  申请人：Gibson Christoph

  公开号：US20100234344A1

  公开（公告）日：2010-09-16

  The present invention is related to compound of the formula (I): or a pharmacologically acceptable salt, solvate, or hydrate thereof, wherein A is a 6-membered heteroaryl having from 1 to 3 heteroatoms, each independently selected from N or O and the other substituents are defined as in the claims.

  本发明涉及公式(I)的化合物或其药理学上可接受的盐、溶剂合物或水合物，其中A是一种具有1至3个杂原子的6元杂环芳基，每个杂原子独立地选自N或O，其它取代基如权利要求所定义。