BRL 56905 | 147009-17-4

• 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: BRL 56905
• 英文别名: (+/-)-3-amino-6-carboxamido-1,2,3,4-tetrahydrocarbazole；6-amino-6,7,8,9-tetrahydro-5H-carbazole-3-carboxamide
• CAS: 147009-17-4
• 化学式: C₁₃H₁₅N₃O
• 分子量: 229.282
• InChiKey: PMQBOSGFSARWCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  84.9
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  调呋酸 、 BRL 56905 以 甲醇 为溶剂， 以24%的产率得到
  参考文献：
  名称：

  [EN] A PROCESS FOR THE PREPARATION OF FROVATRIPTAN AND FROVATRIPTAN SUCCINATE AND THEIR SYNTHETIC INTERMEDIATES
  [FR] PROCÉDÉ POUR LA PRÉPARATION DE FROVATRIPTAN ET DE SUCCINATE DE FROVATRIPTAN ET DE LEURS PRODUITS INTERMÉDIAIRES DE SYNTHÈSE

  摘要：

  本发明涉及活性药物成分frovatriptan及其药用可接受的盐。具体而言，涉及制备frovatriptan及其合成中间体的高效过程，这些过程适用于大规模商业生产，并提供具有改善产量和纯度的所需产品。

  公开号：

  WO2010122343A1
• 作为产物：
  描述：

  (+/-)-6-carboxamido-3-phthalimido-1,2,3,4-tetrahydrocarbazole 在 肼 、 三乙胺 作用下， 以 异丙醇 为溶剂， 反应 0.5h， 以92%的产率得到BRL 56905
  参考文献：
  名称：

  [EN] A PROCESS FOR THE PREPARATION OF FROVATRIPTAN AND FROVATRIPTAN SUCCINATE AND THEIR SYNTHETIC INTERMEDIATES
  [FR] PROCÉDÉ POUR LA PRÉPARATION DE FROVATRIPTAN ET DE SUCCINATE DE FROVATRIPTAN ET DE LEURS PRODUITS INTERMÉDIAIRES DE SYNTHÈSE

  摘要：

  本发明涉及活性药物成分frovatriptan及其药用可接受的盐。具体而言，涉及制备frovatriptan及其合成中间体的高效过程，这些过程适用于大规模商业生产，并提供具有改善产量和纯度的所需产品。

  公开号：

  WO2010122343A1

文献信息

• [EN] SUBSTITUTED 2-CARBONYLAMINO-6-PIPERIDINAMINOPYRIDINES AND SUBSTITUTED 1-CARBONYLAMINO-3-PIPERIDINAMINOBENZENES AS 5-HT1F AGONISTS<br/>[FR] 2-CARBONYLAMINO-6-PIPERIDINAMINOPYRIDINES SUBSTITUES ET 1-CARBONYLAMINO-3-PIPERIDINAMINOBENZENES SUBSTITUES UTILISES EN TANT QU'AGONISTES DE 5-HT1F
  申请人：LILLY CO ELI

  公开号：WO2005035499A1

  公开（公告）日：2005-04-21

  ABSTRACT The present invention relates to compounds of formula I: (I) or a pharmaceutically acceptable acid addition salt thereof, where; X is C(R3c= or N=; R1 is C2-C6 alkyl, substituted C2-C6 alkyl, C3-C7 cycloalkyl, substituted C3-C7 cycloalkyl, phenyl, substituted phenyl, heterocycle, or substituted heterocycle; R2 is hydrogen, C1-C3 n-alkyl, C3-C6 cycloalkyl-C1-C3 alkyl, or a group of formula II (II) provided that when R1 is C2-C6 alkyl or substituted C2-C6 alkyl, R2 is hydrogen or methyl; R3a, R3b, and, when X is C(R3c)=, R3c, are each independently hydrogen, fluoro, or methyl, provided that no more than one of R3a, R3b, and R3c may be other than hydrogen; R4 is hydrogen or C1-C3 alkyl; R5 is hydrogen, C1-C3 alkyl, or C3-C6 cycloalkylcarbonyl, provided that when R3a is other than hydrogen, R5 is hydrogen; R6 is hydrogen or C1-C6 alkyl; and n is an integer from 1 to 6 inclusively. The compounds of the present invention are useful for activating 5-HT1F receptors, inhibiting neuronal protein extravasation, and for the treatment or prevention of migraine in a mammal.

  本发明涉及以下化合物的公式I：（I）或其药学上可接受的酸加盐，其中；X为C（R3c=或N=；R1为C2-C6烷基，取代的C2-C6烷基，C3-C7环烷基，取代的C3-C7环烷基，苯基，取代的苯基，杂环烷基，或取代的杂环烷基；R2为氢，C1-C3正烷基，C3-C6环烷基-C1-C3烷基，或公式II的基团（II），但当R1为C2-C6烷基或取代的C2-C6烷基时，R2为氢或甲基；R3a，R3b，和当X为C（R3c）=时，R3c，各自独立地为氢，氟，或甲基，但R3a，R3b，和R3c中的最多一个可能不是氢；R4为氢或C1-C3烷基；R5为氢，C1-C3烷基，或C3-C6环烷基甲酰，但当R3a不是氢时，R5为氢；R6为氢或C1-C6烷基；n为1到6的整数（包括1和6）。本发明的化合物可用于激活5-HT1F受体，抑制神经蛋白外渗，以及用于治疗或预防哺乳动物的偏头痛。
• [EN] (PIPERIDINYLOXY)PHENYL, (PIPERIDINYLOXY)PYRIDINYL, (PIPERIDINYLSULFANYL)PHENYL AND (PIPERIDINYLSULFANYL)PYRIDINYL COMPOUNDS AS 5-HT1F AGONISTS<br/>[FR] COMPOSES (PIPERIDINYLOXY)PHENYLE, (PIPERIDINYLOXY)PYRIDINYLE, (PIPERIDINYLSULFANYL)PHENYLE ET (PIPERIDINYLSULFANYL)PYRIDINYLE UTILISES COMME AGONISTES DES RECEPTEURS 5-HT1F
  申请人：LILLY CO ELI

  公开号：WO2004094380A1

  公开（公告）日：2004-11-04

  The present invention relates to compounds of formula 1: and pharmaceutically acceptable acid addition sails thereof. The compounds of the present invention are useful for activating 5-HTIF receptors, inhibiting neuronal protein extravasation, and for the treatment or preverition of migraine in mammals, particularly humans.

  本发明涉及公式1的化合物及其药用可接受的酸盐。本发明的化合物可用于激活5-HTIF受体，抑制神经蛋白外渗，并用于治疗或预防哺乳动物，尤其是人类的偏头痛。
• [EN] COMPOSITIONS AND METHODS OF SYNTHESIS OF PYRIDINOYLPIPERIDINE 5-HT1F AGONISTS<br/>[FR] COMPOSITIONS ET MÉTHODES DE SYNTHÈSE D'AGONISTES DES RÉCEPTEURS 5-HT1F DÉRIVÉS DE LA PYRIDINOYLPIPÉRIDINE
  申请人：COLUCID PHARMACEUTICALS INC

  公开号：WO2011123654A1

  公开（公告）日：2011-10-06

  The present invention provides a novel polymorph of the hemisuccinate salt of 2,4,6-trifluoro-N-[6-(1-methyl-piperidine-4-carbonyl)-pyridin-2-yl]-benzamide (Form A) characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure. This polymorph is useful in pharmaceutical compositions, for example, for the treatment and prevention of migraine. The invention also provides a process for the synthesis of pyridinoylpiperidine compounds of Formula I in high yield and high purity. In particular, the provides a process for the preparation of 2,4,6-trifluoro-N-[6-(1-methyl-piperidine-4-carbonyl)-pyridin-2-yl]-benzamde, its hemisuccinate salt and polymorph (Form A).

  本发明提供了2,4,6-三氟-N-[6-(1-甲基哌啶-4-羰基)-吡啶-2-基]-苯甲酰半琥酸盐的新型多晶形态（A型），其具有独特的X射线衍射图样和差示扫描量热分析曲线，以及独特的晶体结构。该多晶形态在药物组合物中具有用途，例如用于治疗和预防偏头痛。该发明还提供了一种高产率和高纯度合成Formula I中吡啶酰哌啶化合物的方法。具体来说，提供了一种制备2,4,6-三氟-N-[6-(1-甲基哌啶-4-羰基)-吡啶-2-基]-苯甲酰半琥酸盐和多晶形态（A型）的方法。
• [EN] PYRIDINOYLPIPERIDINES AS 5-HT1F AGONISTS<br/>[FR] PYRIDINOYLPIPERIDINES UTILISEES COMME AGONISTES DE 5-HT1F
  申请人：LILLY CO ELI

  公开号：WO2003084949A1

  公开（公告）日：2003-10-16

  The present invention relates to compounds of formula I:or pharmaceutically acceptable acid addition salts thereof, where;R1 is C1-C6 alkyl, substituted C1-C6 alkyl, C3-C7 cycloalkyl, substituted C3-C7 cycloalkyl, C3-C7 cycloalkyl-C1-C3 alkyl, substituted C3-C7 cycloalkyl-C1-C3 alkyl, phenyl, substituted phenyl, heterocycle, or substituted heterocycle;R2 is hydrogen, C1-C3 alkyl, C3-C6 cycloalkyl-C1-C3 alkyl, or a group of formula II II;R3 is hydrogen or C1-C3 alkyl; R4 is hydrogen, halo, or C1-C3 alkyl;R5 is hydrogen or C1-C3 alkyl; R6 is hydrogen or C1-C6 alkyl; and n is an integer from 1 to 6 inclusively. The compounds of the present invention are useful for activating 5-HT1F receptors, inhibiting neuronal protein extravasation, and for the treatment or prevention of migraine in a mammal. The present invention also relates to a process for the synthesis of intermediates in the synthesis of compounds of Formula I.

  本发明涉及以下公式的化合物：或其药学上可接受的酸盐，其中; R1是C1-C6烷基，取代的C1-C6烷基，C3-C7环烷基，取代的C3-C7环烷基，C3-C7环烷基-C1-C3烷基，取代的C3-C7环烷基-C1-C3烷基，苯基，取代的苯基，杂环，或取代的杂环; R2是氢，C1-C3烷基，C3-C6环烷基-C1-C3烷基，或公式II的基团 II; R3是氢或C1-C3烷基; R4是氢，卤素，或C1-C3烷基; R5是氢或C1-C3烷基; R6是氢或C1-C6烷基; n是从1到6的整数（包括1和6）。本发明的化合物可用于激活5-HT1F受体，抑制神经蛋白外渗，并用于哺乳动物偏头痛的治疗或预防。本发明还涉及一种合成公式I化合物合成中间体的方法。
• [EN] SUBSTITUTED (4-AMINOCYCLOHEXEN-1-YL)PHENYL AND (4-AMINOCYCLOHEXEN-1-YL)PYRIDINYL COMPOUNDS AS 5-HT1F AGONISTS<br/>[FR] COMPOSES (4-AMINOCYCLOHEXEN-1-YL)PHENYLE ET (4-AMINOCYCLOHEXEN-1-YL)PYRIDINYLE SERVANT D'AGONISTES DE 5-HT1F
  申请人：LILLY CO ELI

  公开号：WO2005061439A1

  公开（公告）日：2005-07-07

  The present invention relates to compounds of formula (I) or a pharmaceutically acceptable acid addition salt thereof, where; X is -C(R4)= or -N=; Ar is phenyl, substituted phenyl, heterocycle, or substituted heterocycle; R1 and R2 are independantly hydrogen or C1-C3 alkyl; R3 is hydrogen, fluoro, or methyl; when X is -C(R4)=, R4 is hydrogen, fluoro, or methyl, provided that no more than one of R3 and R4 may be other than hydrogen; and R5 is hydrogen, methyl, or ethyl. The compounds of the present invention are useful for activating 5-HT1F receptors, inhibiting dural protein extravasation, and for the treatment or prevention of migraine in a mammal.

  本发明涉及式(I)的化合物或其药用可接受的酸盐，其中：X为-C(R4)=或-N=；Ar为苯基、取代苯基、杂环或取代杂环；R1和R2独立地为氢或C1-C3烷基；R3为氢、氟或甲基；当X为-C(R4)=时，R4为氢、氟或甲基，但R3和R4中不超过一个可以是氢以外的其他基团；R5为氢、甲基或乙基。本发明的化合物可用于激活5-HT1F受体，抑制硬脑膜蛋白外渗，以及用于治疗或预防哺乳动物的偏头痛。