6-Dimethylamino-6,7,8,9-tetrahydro-5H-carbazol-3-ol | 32212-00-3

• 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: 6-Dimethylamino-6,7,8,9-tetrahydro-5H-carbazol-3-ol
• 英文别名: 3-(Dimethylamino)-6-hydroxy-1,2,3,4-tetrahydrocarbazole；LY 306258；6-dimethylamino-5,6,7,8-tetrahydro-carbazol-3-ol；6-hydroxy-3-dimethylamino-1,2,3,4-tetrahydrocarbazole；3-(Dimethylamino)-2,3,4,9-tetrahydro-1h-carbazol-6-ol；6-(dimethylamino)-6,7,8,9-tetrahydro-5H-carbazol-3-ol
• CAS: 32212-00-3
• 化学式: C₁₄H₁₈N₂O
• 分子量: 230.31
• InChiKey: ZQUXUQXIXIVEQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  39.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N,N-dimethyl-9-phenylmethoxy-1,2,3,4-tetrahydrocarbazol-3-amine;hydrochloride 以50%的产率得到
  参考文献：
  名称：

  MOORADIAN A.; DUPONT P. E.; HLAVAC A. G.; ACETO M. D.; PEARL J., J. MED. CHEM. , 1977, 20, NO 4, 487-492

  摘要：

  DOI：

文献信息

• Tetrahydrocarbazoles and their use
  申请人：Sterling Drug Inc.

  公开号：US04224335A1

  公开（公告）日：1980-09-23

  There are disclosed novel 3-amino(and substituted amino)-hydroxy (and dihydroxy)-1,2,3,4-tetrahydrocarbazoles having positive inotropic activity and methods and compositions for the use thereof in treating the failing heart in mammals afflicted with congestive heart failure.

  本发明涉及具有正肌力作用的新型3-氨基（和取代氨基）-羟基（和二羟基）-1,2,3,4-四氢咔唑类化合物，以及在治疗患有充血性心力衰竭的哺乳动物中使用它们的方法和组合物。
• Use of 5-HT1F-receptor agonists for the treatment of migraine
  申请人：ELI LILLY AND COMPANY

  公开号：EP0705600A1

  公开（公告）日：1996-04-10

  The present invention provides a method for the treatment of migraine and associated disorders which relies on a novel mechanism of action. By treating a migraineur with compounds or compositions which are selective agonists of 5-HT1F receptors relative to other serotonin receptors which produce unwanted effects like vasoconstriction, the neurogenic meningeal extravasation which leads to the pain of migraine is inhibited and the physiological liabilities of compounds exhibiting vasoconstriction or other side effects are avoided.

  本发明提供了一种治疗偏头痛及相关疾病的方法，该方法依赖于一种新的作用机制。通过使用5-HT1F受体选择性激动剂的化合物或组合物治疗偏头痛患者，相对于其他会产生血管收缩等不良反应的5-羟色胺受体，可抑制导致偏头痛疼痛的神经源性脑膜外渗，并避免表现出血管收缩或其他副作用的化合物的生理缺陷。
• 3-(1,2,3,6-tetrahydro-(1-alkylenearyl)-4-pyridinyl)- and 3-(1-alkylenearyl)-4-piperidinyl-1h-indoles: new 5-HT1f agonists
  申请人：ELI LILLY AND COMPANY

  公开号：EP0714894A1

  公开（公告）日：1996-06-05

  This invention provides novel 5-HT1F agonists of formula I which are useful for the treatment of migraine and associated disorders.

  本发明提供了式 I 的新型 5-HT1F 激动剂，可用于治疗偏头痛及相关疾病。
• 5-Substituted-3-(1,2,3,6-tetrahydropyridin-4-yl)- and 3-(piperidin-4-yl)-1h-indoles: new 5-ht1f agonists
  申请人：ELI LILLY AND COMPANY

  公开号：EP0733628A1

  公开（公告）日：1996-09-25

  This invention provides novel 5-HT1F agonists which are useful for the treatment of migraine and associated disorders. The compounds have the formula in which A-B is -CH-CH2- or -C=CH-; R is H or C1-C6 alkyl; R1 is H or C1-C4 alkyl; X is -S-R2, -C(O)R3, -C(O)NR4R15, -NR5R6, -NR7SO2R8, -NHC(Q)NR10R11, -NHC(O)OR12 or -NR13C(O)R14; where Q is O, or S; R2 is phenyl, substituted phenyl, phenyl(C1-C4 alkylene), phenyl(C1-C4 alkylene) substituted in the phenyl ring, or pyridinyl; R3 is C1-C6 alkyl, phenyl(C1-C4 alkylene), phenyl(C1-C4 alkylene) substituted in the phenyl ring, naphthyl, N-methyl-N-methoxyamino, heteroaryl, substituted heteroaryl, heteroaryl(C1-C4 alkyl), or substituted heteroaryl(C1-C4 alkyl); R4 is heteroaryl, substituted heteroaryl, heteroaryl(C1-C4 alkyl), or substituted heteroaryl(C1-C4 alkyl); R4 and R15 taken together with the nitrogen atom form a pyrrolidine, piperidine, substituted piperidine, piperazine, 4-substituted piperazine, morpholine or thiomorpholine ring; R5 and R6 are both trifluoromethanesulfonyl; R7 is H or C1-C4 alkyl; R8 is C1-C4 alkyl, phenyl, substituted phenyl, or di(C1-C4 alkyl)amino; R10 and R11 are independently selected from the group consisting of C1-C6 alkyl, C3-C6 alkenyl, C3-C8 cycloalkyl, phenyl, substituted phenyl, phenyl(C1-C4 alkylene), phenyl(C1-C4 alkylene) substituted in the phenyl ring, ((C1-C4 alkyl or C1-C4 alkoxycarbonyl substituted)C1-C4 alkyl)phenyl, C1-C4 alkyl α-substituted with C1-C4 alkoxycarbonyl; or R10 and R11 taken together with the nitrogen atom form a pyrrolidine, piperidine, piperazine, 4-substituted piperazine, morpholine or thiomorpholine ring; R12 is C1-C6 alkyl, C3-C6 alkenyl, phenyl, substituted phenyl, C3-C8 cycloalkyl, C1-C4 alkyl ω-substituted with C1-C4 alkoxy; R13 is H or C1-C4 alkyl; R14 is C1-C10 alkyl substituted with up to three substituents selected from the group consisting of hydroxy, C1-C4 alkoxy, halo, aryloxy, C1-C4 alkoxycarbonyl and heteroaryloxy, C2-C10 alkenyl, C2-C10 alkynyl, C3-C8 cycloalkyl, phenyl, substituted phenyl, naphthyl, phenyl(C1-C4 alkylene), phenyl(C1-C4 alkylene) substituted on the phenyl ring, 2-phenylethylen-1-yl, diphenylmethyl, benzofused C4-C8 cycloalkyl, C1-C4 alkylene ω-substituted with C3-C6 cycloalkyl, or a heterocycle; R15 is H or C1-C6 alkyl;    subject to the proviso that when R7 is H, R8 is not C1-C4 alkyl; and pharmaceutically acceptable acid addition salts and solvates thereof.

  本发明提供了可用于治疗偏头痛及相关疾病的新型 5-HT1F 激动剂。这些化合物的化学式为 其中 A-B是-CH-CH2-或-C=CH-； R 是 H 或 C1-C6 烷基； R1 是 H 或 C1-C4 烷基； X 是-S-R2、-C(O)R3、-C(O)NR4R15、-NR5R6、-NR7SO2R8、-NHC(Q)NR10R11、-NHC(O)OR12 或-NR13C(O)R14； 其中 Q 是 O 或 S R2 是苯基、取代的苯基、苯基(C1-C4 亚烷基)、苯基环上取代的苯基(C1-C4 亚烷基)或吡啶基； R3 是 C1-C6 烷基、苯基（C1-C4 亚烷基）、在苯基环中取代的苯基（C1-C4 亚烷基）、萘基、N-甲基-N-甲氧基氨基、杂芳基、取代的杂芳基、杂芳基（C1-C4 烷基）或取代的杂芳基（C1-C4 烷基）； R4 是杂芳基、取代的杂芳基、杂芳基（C1-C4 烷基）或取代的杂芳基（C1-C4 烷基）； R4 和 R15 与氮原子一起形成吡咯烷、哌啶、取代的哌啶、哌嗪、4-取代的哌嗪、吗啉或硫代吗啉环； R5 和 R6 都是三氟甲烷磺酰基； R7 是 H 或 C1-C4 烷基； R8 是 C1-C4 烷基、苯基、取代苯基或二(C1-C4 烷基)氨基； R10 和 R11 独立地选自由 C1-C6 烷基、C3-C6 烯基、C3-C8 环烷基、苯基、取代苯基、苯基(C1-C4 亚烷基)、苯基环上取代的苯基(C1-C4 亚烷基)、((C1-C4 烷基或 C1-C4 烷氧基羰基取代的)C1-C4 烷基)苯基、被 C1-C4 烷氧基羰基 α 取代的 C1-C4 烷基组成的组；或 R10 和 R11 与氮原子一起形成吡咯烷、哌啶、哌嗪、4-取代哌嗪、吗啉或硫代吗啉环； R12 是 C1-C6 烷基、C3-C6 烯基、苯基、取代苯基、C3-C8 环烷基、ω-被 C1-C4 烷氧基取代的 C1-C4 烷基； R13 是 H 或 C1-C4 烷基； R14 是最多被三个取代基取代的 C1-C10 烷基，这三个取代基选自由羟基、C1-C4 烷氧基、卤代、芳氧基、C1-C4 烷氧羰基和杂芳氧基、C2-C10 烯基、C2-C10 炔基、C3-C8 环烷基、苯基、取代苯基、萘基、烷基酚和烷基酚组成的组、取代的苯基、萘基、苯基（C1-C4 亚烷基）、苯基环上取代的苯基（C1-C4 亚烷基）、2-苯基乙烯-1-基、二苯甲基、苯并 C4-C8 环烷基、被 C3-C6 环烷基取代的 C1-C4 亚烷基 ω 或杂环； R15 是 H 或 C1-C6 烷基； 但当 R7 为 H 时，R8 不是 C1-C4 烷基；以及其药学上可接受的酸加成盐和溶剂。
• 6-substituted-1,2,3,4-tetrahydro-9H-carbazoles and 7-substituted-10H-cyclohepta(7,6-B)indoles
  申请人：ELI LILLY AND COMPANY

  公开号：EP0749962A1

  公开（公告）日：1996-12-27

  The present invention provides novel agonists of the serotonin 5-HT1F receptor of formula I which are useful in a method of inhibiting neuronal protein extravasation without causing vasoconstriction. wherein: R1 and R2are independently hydrogen, C1-C4 alkyl, or -CH2CH2-Aryl where Aryl is phenyl, phenyl monosubstituted with halo, or 1-(C1-C6 alkyl) pyrazol-4-yl; Xis -OH, -NHC(O)R3, -NHC(Y)NHR4, -NHC(O)OR5, -C(O)R6 or -NHSO2R7; R3is C1-C6 alkyl, C2-C6 alkenyl, C3-C8 cycloakyl, phenyl, substituted phenyl, naphthyl, (C1- C4 alkylene)phenyl, thienylmethyl, or a heterocycle; R4is C1-C6 alkyl, phenyl, or phenyl disubstituted with halo; R5is C1-C6 alkyl, C2-C6 alkenyl, benzyl or phenyl monosubstituted with halo; R6is C1-C6 alkyl, phenyl, or phenyl monosubstituted with halo or C1-C4 alkoxy; R7is dimethylamino, phenyl or phenyl monosubstituted with halo or C1-C4 alkyl; mis 0 or 1; nis 1 or 2; and Yis S or O; and parmaceutically acceptable salts and hydrates thereof, providing: Xis not -OH when m is 0, n is 1, and R1 and R2 are independently hydrogen or C1-C6 alkyl; and R3is not C1-C6 alkyl when m is 0, n is 1, and R1 and R2 are independently hydrogen or C1-C6 alkyl.

  本发明提供了式 I 的新型血清素 5-HT1F 受体激动剂，可用于抑制神经元蛋白外渗而不引起血管收缩的方法。 其中 R1 和 R2 独立地为氢、C1-C4 烷基或-CH2CH2-芳基，其中芳基为苯基、卤代单取代苯基或 1-(C1-C6烷基)吡唑-4-基； X为-OH、-NHC(O)R3、-NHC(Y)NHR4、-NHC(O)OR5、-C(O)R6 或-NHSO2R7； R3 是 C1-C6 烷基、C2-C6 烯基、C3-C8 环烷基、苯基、取代苯基、萘基、（C1-C4 亚烷基）苯基、噻吩甲基或杂环； R4 是 C1-C6 烷基、苯基或与卤代物二取代的苯基； R5 是被卤素单取代的 C1-C6 烷基、C2-C6 烯基、苄基或苯基； R6 是卤代或 C1-C4 烷氧基单取代的 C1-C6 烷基、苯基或苯基； R7 是二甲基氨基、苯基或与卤素或 C1-C4 烷基单取代的苯基； mis为 0 或 1； n 是 1 或 2；以及 Y 是 S 或 O；以及它们的法玛西亚可接受盐和水合物，条件是 当 m 为 0，n 为 1，且 R1 和 R2 独立为氢或 C1-C6 烷基时，X 不是-OH；以及 当 m 为 0，n 为 1，且 R1 和 R2 独立为氢或 C1-C6 烷基时，R3 不是 C1-C6 烷基。