8-cyclohexyl-5,6,10,11-tetrahydro-4H-pyrido-[4',3':4,5]-pyrrolo-[3,2,1-ij]quinoline hydrochloride | 121933-13-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 8-cyclohexyl-5,6,10,11-tetrahydro-4H-pyrido-[4',3':4,5]-pyrrolo-[3,2,1-ij]quinoline hydrochloride
• 英文别名: 14-Cyclohexyl-1,13-diazatetracyclo[7.6.1.05,16.010,15]hexadeca-5(16),6,8,10(15),13-pentaene;hydrochloride
• CAS: 121933-13-9
• 化学式: C₂₀H₂₄N₂*ClH
• 分子量: 328.885
• InChiKey: NRHFOPLANBYVLO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.93
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  17.3
• 氢给体数：
  1
• 氢受体数：
  1

文献信息

• 8,9-anellated-1,2,3,4-tetrahydro-beta-carboline derivatives
  申请人：DUPHAR INTERNATIONAL RESEARCH B.V

  公开号：EP0300541A1

  公开（公告）日：1989-01-25

  The invention relates to new 8,9-anellated-1,2,3,4-­tetrahydro-β-carboline derivatives of the formula wherein the symbols have the following meanings: R₁ is straight or branched alkyl having 1-6 C-atoms, fluorinated or hydroxylated alkyl having 1-6 C-atoms, phenylalkyl having 1-6 C-atoms in the alkyl group, the phenyl group of which may optionally by substituted, or two alkyl groups R₁ bonded to adjacent carbon atoms together constitute a ring of 5-7 carbon atoms, which ring may be substituted with alkyl groups having 1-3 C-­atoms, or R₁ is straight or branched alkenyl or alkynyl having 2-6 C-atoms, which groups may comprise one or more fluorine atoms, or cycloalkyl having 3-6 C-atoms which are substituted with 0-4 methyl groups, or R₁ is straight or branched alkoxy or alkylthio having 1-6 C-­atoms which may be substituted with one or more fluorine atoms of hydroxyl groups, or with one optionally sub­stituted phenyl group, or two alkoxy groups and/or al­kylthio groups bonded to two adjacent carbon atoms may form a ring consisting of 5-7 ring atoms which may be substituted with hydroxymethyl, alkoxy or alkoxyalkyl groups having 1-6 C-atoms, or R₁ is a cycloalkoxy group or cycloalkylthio group having 3-6 C-atoms which may be substituted with 1-4 methyl groups, or R₁ is straight or branched alkoxy-, alkylthio- or alkylsulphonylalkyl having 2-6 C-atoms which may comprise one or more fluorine atoms or hydroxyl groups, or R₁ is an alkoxy-­carbonylmethyl group having 1-6 C-atoms in the alkoxy group, or R₁ is a group R₈R₉N-CO-CH₂-, R₈R₉N-CO- or R₈R₉N-SO₂ wherein R₈ and R₉ independently of each other are hydrogen, alkyl having 1-3 C-atoms, or, together with the nitrogen atom, form a heterocyclic 5- or 6-­ring, or R₁ is hydroxy, halogen, cyano, straight or branched alkoxycarbonyl having 1-6 C-atoms in the alkoxy group, cycloalkylsulphonyl having 3-8 C-atoms which may be substituted with 1-4 methyl groups; n has the value 0-3; R₂ + R₃ together with the carbon atom and the nitrogen atom to which they are bonded and the intermediate carbon atom constitute a heterocyclic group consisting of 5-8 ring atoms which, in addition to the nitrogen atom already present, may comprise a second hetero atom from the group N, O, S, S-O or SO₂, and which may be substituted with 1-3 alkyl groups having 1-4 C-atoms which can form a spiroalkyl group having 2-5 C-atoms, or the hetero group may be substituted with a phenyl group comprising 0-3 groups R₁₀, wherein R₁₀ is alkyl or alkoxy having 1-3 C-atoms, halogen, trifluoromethyl, cyano or hydroxy and two alkyl groups or alkoxy groups R₁₀ bonded to adjacent carbon atoms may for a ring anellated with the phenyl group and consisting of 5-7 ring atoms, which ring may be substituted with alkyl or alkoxy having 1-3 C-atoms, or with akoxyalkyl having 1-6 C-atoms, and the ring formed by R₂ + R₃ may be anellated with a saturated or unsaturated carbocyclic or heterocy­clic ring consisting of 5- or 6-ring atoms which may be substituted with halogen or alkyl having 1-4 C-atoms; R₄ is hydrogen, straight or branched alkyl having 1-8 C-­atoms, alkoxy- or alkylthioalkyl having 2-6 C-atoms, alkenyl or alkynyl having 2-8 C-atoms, which groups may be substituted with one or more fluorine atoms or hydroxy groups, or with one phenyl group containing 0-3 groups R₁₀, or cycloalkyl group having 3-7 C-atoms, or R₄ is cycloalkyl having 3-8 C-atoms which may be substituted with one or more fluorine atoms, alkyl groups having 1-4 C-atoms, cycloalkyl groups having 3-5 C-atoms, or R₄ is cycloalkenyl having 5-7 C-atoms which may be substituted with 1-4 methyl groups, or R₄ is straight or branched alkoxycarbonylalkyl having 0-6 C-­atoms in the alkoxy group and 1-3 C-atoms in the alkyl group, or R₄ is a group R₈R₉N-CO-R₁₁- or R₈R₉N-SO-R₁₁-, wherein R₈ and R₉ have the above-mentioned meanings and R₁₁ is alkyl having 1-3 C-atoms, or R₄ is alkylsulpho­nylalkyl having 1-3 C-atoms per alkyl group, or a phenylsulphonylalkyl group having 1-3 C-atoms in the alkyl group and the phenyl group comprises 0-3 groups R₁₀, or R₄ is a phenyl group substituted with 0-4 groups R₁₂, wherein R₁₂ is straight or branched alkyl having 1-6 C-atoms which may be substituted with one or more fluorine atoms or hydroxyl groups, or with one cyano group, or with straight or branched alkoxycarbonyl having 0-6 C-atoms in the alkoxy group, or with a group R₈R₉N-CO- or R₈R₉N-SO₂-, wherein R₈ and R₉ have the above-mentioned meanings, or two groups R₁₂ bonded to adjacent carbon atoms form a ring anellated with the phenyl group and consisting of 5-7 ring atoms, which ring may be substituted with 1-3 alkyl groups having 1-3 C-atoms, or R₁₂ is straight or branched alkyl (1-4 C)-­oxy-alkyl(0-3 C), alkyl (1-4 C)-thio-alkyl(0-3 C) or alkyl (1-4 C)-sulphonylalkyl (0-3 C) which groups may comprise one or more fluorine atoms or hydroxyl groups, or of which two alkoxy groups or alkylthio groups bonded to adjacent carbon atoms form a ring which consists of 5-7 ring atoms and may be substituted with alkyl or alkoxy having 1-3 C-atoms, or with hydroxymethyl, or with alkoxyalkyl having 2-6 C-atoms, or R₁₂ is cycloal­koxy or cycloalkylthio having 3-7 C-atoms which may be substituted with 0-4 methyl groups, or R₁₂ is cycloalkyl having 3-7 C-atoms in which one or more fluorine atoms or methyl groups may be present, or R₁₂ is straight or branched alkoxycarbonyl having 1-6 C-atoms in the alkoxy group, a groups R₈R₉N-CO- or R₈R₉N-SO₂- wherein R₈ and R₉ have the above-mentioned meanings, or R₁₂ is halogen or hydroxy, or R₄ is mono- or bicyclic heteroaryl group in which N and/or O and/or S may be present as hetero atoms, and the ring(s) may be substituted with alkyl, alkoxy or alkylthio having 1-3 C-atoms, halogen, keto oxygen atom, cyano and/or CF₃; R₅ is hydrogen or straight or branched alkyl having 1-6 C-atoms; or R₄ + R₅, together with the carbon atom to which they are bonded, may form a carbocyclic or heterocyclic ring consisting of 5-7 ring atoms which may comprise N, O, S, So or SO₂ as a hetero atom; R₆ is hydrogen, straight or branched alkyl having 1-6 C-atoms which may be substituted with one or more hydroxyl groups or with one optionally substituted phenyl group or alkoxycarbonyl group having 1-3 C-atoms in the alkoxy group, or R₆ is a straight or branched alkenyl or alkynyl having 2-6 C-atoms, or a group -CO-X, wherein X is straight or branched alkyl, alkenyl, alkynyl or alkoxy having 1-6 C-atoms, or an optionally substituted phenyl group, or R₆ is an amino acid radical of the formula -CO-CHR₁₃-NH-R₁₄, wherein R₁₃ is alkyl and R₁₄ is hydrogen, alkanoyl or alkoxycarbonyl having 1-4 C-atoms; R₇ is alkyl having 1-3 C-atoms, or one group R₇ is an alkoxycarbonyl group having 1-3 C-atoms in the alkoxy group, or the hydroxymethyl group; and p has the value 0-4, and the salts and prodrugs thereof. It has been found that these compounds have good fibrinolytic properties and may be used as orally active fibrinolytics.

  本发明涉及一种新的8,9-桥连的1,2,3,4-四氢-β-咔啉衍生物，其结构如下所示，其中各符号具有以下含义： - **R₁** 可以是直链或支链的烷基（含1-6个碳原子）、氟代烷基或羟基烷基（含1-6个碳原子）、苯基烷基（含1-6个碳原子，其苯基部分可选地被取代），或者两个相邻碳原子上的R₁基团共同形成一个含5-7个碳原子的环，该环可被含1-3个碳原子的烷基取代；**R₁** 也可以是直链或支链的烯基或炔基（含2-6个碳原子），这些基团中可含有一个或多个氟原子；**R₁** 还可以是含3-6个碳原子的环烷基，其上可被0-4个甲基取代；或者**R₁** 是直链或支链的烷氧基或硫代烷基（含1-6个碳原子），这些基团中可含有一个或多个氟原子或羟基，或被一个可选地取代的苯基取代；两个相邻碳原子上的烷氧基和/或硫代烷基基团可形成一个由5-7个环原子组成的环，该环可被羟甲基、烷氧基或含1-6个碳原子的烷氧基烷基取代；**R₁** 也可以是含3-6个碳原子的环烷氧基或硫代环烷基，这些基团可被1-4个甲基取代；或者**R₁** 是直链或支链的烷氧基、硫代烷基或磺酰烷基（含2-6个碳原子），这些基团中可含有一个或多个氟原子或羟基；**R₁** 也可以是含1-6个碳原子的烷氧基羰基甲基；**R₁** 还可以是**R₈R₉N-CO-CH₂-**、**R₈R₉N-CO-** 或 **R₈R₉N-SO₂** 的基团，其中**R₈** 和 **R₉** 独立地为氢、含1-3个碳原子的烷基，或者与氮原子一起形成一个含5或6个环原子的杂环；或者**R₁** 是羟基、卤素、氰基、直链或支链的烷氧基羰基（其烷氧基部分含1-6个碳原子）、含3-8个碳原子的环烷基磺酰基（可被1-4个甲基取代）。 - **n** 的取值范围为0-3。 - **R₂ + R₃** 与它们所连接的碳原子和氮原子以及中间的碳原子共同构成一个含有5-8个环原子的杂环，除了已有的氮原子外，该环还可包含一个来自N、O、S、S-O或SO₂组的第二个杂原子，并可被1-3个含1-4个碳原子的烷基取代，这些烷基可以形成一个含2-5个碳原子的螺烷基；该杂环还可以被一个含0-3个**R₁₀** 基团的苯基取代，其中**R₁₀** 是含1-3个碳原子的烷基或烷氧基、卤素、三氟甲基、氰基或羟基；两个相邻碳原子上的**R₁₀** 基团可形成一个与苯环桥连的由5-7个环原子组成的环，该环可被含1-3个碳原子的烷基或烷氧基取代，或者被含1-6个碳原子的烷氧基烷基取代；由**R₂ + R₃** 形成的环还可以与一个由5或6个环原子组成的饱和或不饱和的碳环或杂环桥连，这些环可以被卤素或含1-4个碳原子的烷基取代。 - **R₄** 是氢、直链或支链的烷基（含1-8个碳原子）、烷氧基或硫代烷基（含2-6个碳原子）、烯基或炔基（含2-8个碳原子），这些基团可被一个或多个氟原子或羟基取代，或被一个含0-3个**R₁₀** 基团的苯基取代，或者**R₄** 是含3-7个碳原子的环烷基；**R₄** 也可以是含3-8个碳原子的环烷基，其上可被一个或多个氟原子、含1-4个碳原子的烷基、含3-5个碳原子的环烷基取代；或者**R₄** 是含5-7个碳原子的环烯基，其上可被1-4个甲基取代；**R₄** 还可以是直链或支链的烷氧基羰基烷基，其烷氧基部分含0-6个碳原子，烷基部分含1-3个碳原子；或者**R₄** 是**R₈R₉N-CO-R₁₁-** 或 **R₈R₉N-SO-R₁₁-** 的基团，其中**R₈** 和 **R₉** 如前所述，**R₁₁** 是含1-3个碳原子的烷基；**R₄** 还可以是每烷基部分含1-3个碳原子的烷基磺酰基烷基，或者含1-3个碳原子的烷基部分的一个苯基磺酰基烷基，其中苯基部分可含有0-3个**R₁₀** 基团；或者**R₄** 是一个含有0-4个**R₁₂** 基团的苯基，其中**R₁₂** 是直链或支链的烷基（含1-6个碳原子），这些基团可被一个或多个氟原子或羟基取代，或者被一个氰基取代，或者被直链或支链的烷氧基羰基（其烷氧基部分含0-6个碳原子）取代，或者被**R₈R₉N-CO-** 或 **R₈R₉N-SO₂-** 的基团取代（**R₈** 和 **R₉** 如前所述）；两个相邻碳原子上的**R₁₂** 基团可形成一个与苯环桥连的由5-7个环原子组成的环，该环可被1-3个含1-3个碳原子的烷基取代；**R₁₂** 还可以是含1-4个碳原子的烷基氧基-含0-3个碳原子的烷基、含1-4个碳原子的硫代烷基-含0-3个碳原子的烷基、或含1-4个碳原子的磺酰基烷基（含0-3个碳原子），这些基团中可含有一个或多个氟原子或羟基；或者**R₁₂** 是含3-7个碳原子的环烷氧基或硫代环烷基，这些基团可被0-4个甲基取代；**R₁₂** 还可以是含3-7个碳原子的环烷基，其中可含有一个或多个氟原子或甲基；或者**R₁₂** 是直链或支链的烷氧基羰基（其烷氧基部分含1-6个碳原子），或者被**R₈R₉N-CO-** 或 **R₈R₉N-SO₂-** 基团取代（**R₈** 和 **R₉** 如前所述）；或者**R₁₂** 是卤素或羟基；**R₄** 还可以是包含N和/或O和/或S作为杂原子的单环或多环杂芳基，这些环可被烷基、烷氧基或硫代烷基（含1-3个碳原子）、卤素、羰基氧原子、氰基和/或CF₃取代。 - **R₅** 是氢、直链或支链的烷基（含1-6个碳原子）。 - **R₄ + R₅** 与它们所连接的碳原子一起可形成一个由5-7个环原子组成的碳环或杂环，其中可包含N、O、S、So或SO₂作为杂原子。 - **R₆** 是氢、直链或支链的烷基（含1-6个碳原子），这些基团可被一个或多个羟基取代，或被一个可选地取代的苯基或烷氧基羰基（其烷氧基部分含1-3个碳原子）取代；**R₆** 还可以是直链或支链的烯基或炔基（含2-6个碳原子），或是一个-CO-X基团，其中**X** 是直链或支链的烷基、烯基、炔基或烷氧基（含1-6个碳原子），或是一个可选地取代的苯基；或者**R₆** 是氨基酸基团，其结构为-CO-CHR₁₃-NH-R₁₄，其中**R₁₃** 是烷基，**R₁₄** 是氢、含1-4个碳原子的烷酰基或烷氧基羰基。 - **R₇** 是含1-3个碳原子的烷基，或者其中一个**R₇** 是含1-3个碳原子的烷氧基羰基，或者是一个羟甲基基团。 - **p** 的取值范围为0-4。 本发明还包括这些化合物的盐和前药。 已经发现，这些化合物具有良好的纤溶活性，并且可以作为口服有效的纤溶药物使用。
• NOVEL SUBSTITUTED BENZIMIDAZOLES
  申请人：Astra Aktiebolag

  公开号：EP0712400A1

  公开（公告）日：1996-05-22
• US5100884A
  申请人：——

  公开号：US5100884A

  公开（公告）日：1992-03-31
• US5328905A
  申请人：——

  公开号：US5328905A

  公开（公告）日：1994-07-12
• [EN] NOVEL SUBSTITUTED BENZIMIDAZOLES<br/>[FR] NOUVELLES BENZINIDAZOLES SUBSTITUEES
  申请人：ASTRA AKTIEBOLAG

  公开号：WO1995032958A1

  公开（公告）日：1995-12-07

  (EN) The novel optically pure compounds, i.e. the single enantiomeric compounds (Ia, Ib), (+)-5-fluoro-2-[[(4-cyclopropylmethoxy-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole and (-)-5-fluoro-2-[[(4-cyclopropylmethoxy-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole or a therapeutically acceptable salt thereof, such as Na+, Mg2+, Li+, K+, Ca2+ and N+(R)4 salts, where R is an alkyl group with 1-4 carbon atoms, processes for the preparation thereof and pharmaceutical preparations containing the compounds as active ingredients, as well as the use of the compounds in pharmaceutical preparations and intermediates obtained by preparing the compounds.(FR) L'invention porte sur de nouveaux composés (Ia, Ib) optiquement purs c'est-à-dire sur les composés énantiomères individuels (+)-5-fluoro-2[[(4-cyclopropylméthoxy-2-pyridinyl)méthyl]sulfinyl]-1H-benzimidazole et (-)-5-fluoro-2-[[(4-cyclopropylméthoxy-2-pyridinyl)méthyl]sulfinyl]-1H-benzimidazole ou l'un de leurs sels thérapeutiquement acceptables tel que Na+, Mg2+, Li+, K+, Ca2+ et N+(R)4, où R représente un groupe alkyle à 1 à 4 atomes de carbone; sur leurs procédés d'obtention, sur des préparations pharmaceutiques les utilisant comme principes actifs, sur l'utilisation desdits composés dans des préparations pharmaceutiques, et sur leurs intermédiaires de préparation.