8-Fluor-5-phenyl-2-methyl-1,2,3,4-tetrahydro-γ-carbolin

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 8-Fluor-5-phenyl-2-methyl-1,2,3,4-tetrahydro-γ-carbolin
• 英文别名: 8-fluoro-2-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole；8-Fluoro-2-methyl-5-phenyl-1H,2H,3H,4H,5H-pyrido[4,3-B]indole；8-fluoro-2-methyl-5-phenyl-3,4-dihydro-1H-pyrido[4,3-b]indole
• 化学式: C₁₈H₁₇FN₂
• mdl: MFCD27214493
• 分子量: 280.345
• InChiKey: BCGBBSHPHTZOCZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  8.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  8-氟-1,3,4,5-四氢-2H-吡啶基-[4,3-b]吲哚-2-羧酸乙酯 在 aluminium hydride 、 sodium carbonate 、 copper(I) bromide 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 8.5h， 生成 8-Fluor-5-phenyl-2-methyl-1,2,3,4-tetrahydro-γ-carbolin
  参考文献：
  名称：

  Neuroleptic activity in 5-aryltetrahydro-.gamma.-carbolines

  摘要：

  A series of 5-aryltetrahydro-gamma-carbolines was prepared by a novel N-arylation procedure and tested for neuroleptic activity in a rat antiamphetamine model. The systematic exploration of structural parameters leading to 8-fluoro-5-(4-fluorophenyl)-2-[4-hydroxy-4-(4-fluorophenyl)butyl]-2,3,5-tetrahydro-1H-pyrido[4,3-b]indole (CP-36,584, flutroline), a potent and long-acting neuroleptic compound, is described. These semirigid compounds provide a new, structurally distinct series with which to probe the conformational requirements for potent activity at the dopamine receptor.

  DOI：

  10.1021/jm00180a011

文献信息

• SUBSTITUTED 2,3,4,5-TETRAHYDRO-1H-PYRIDO[4,3-B]INDOLES, METHODS FOR THE PRODUCTION AND USE THEREOF
  申请人：Alla Chem, LLC.

  公开号：EP2145887A2

  公开（公告）日：2010-01-20

  The invention relates to antagonists of serotonin 5-HT6 receptors simultaneously regulating homeostasis of Ca+2 ions in cells, representing substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of the general formula 1, pharmaceutically acceptable salts and/or hydrate thereof. In the general formula 1: R1 represents amino group substituent selected from optionally substituted C1-C5 alkyl; R2i is one or more substituents selected from hydrogen, halogen, C1-C3 alkyl, CF3, OCF3; Ar is phenyl optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, substituted amino group, or CF3; or optionally substituted aromatic 6-membered heterocycle comprising 1-2 nitrogen atoms in the cycle; W represents ethylene group -CH2-CH2-, ethenyl group -CH=CH-, or ethynyl group -C≡C-. The invention also relates to the novel compounds selected from the compounds of the general formula 1, methods for their preparation, pharmaceutical compositions and methods of their use.

  本发明涉及5-羟色胺5-HT6受体的拮抗剂，同时调节细胞中Ca+2离子的平衡，代表通式1的取代的2,3,4,5-四氢-1H-吡啶并[4,3-b]吲哚、其药学上可接受的盐和/或水合物。在通式 1 中 R1代表选自任选取代的C1-C5烷基的氨基基团取代基；R2i是一个或多个选自氢、卤素、C1-C3烷基、CF3、OCF3的取代基；Ar是任选被卤素、C1-C6烷基、C1-C6烷氧基、取代的氨基基团或CF3取代的苯基；或任选取代的在循环中包含1-2个氮原子的芳香族6元杂环；W代表乙烯基-CH2-CH2-、乙烯基-CH＝CH-或乙炔基-C≡C-。本发明还涉及选自通式 1 化合物的新型化合物、其制备方法、药物组合物及其使用方法。
• LIGANDS OF ALPHA-ADRENOCEPTORS AND OF DOPAMINE, HISTAMINE, IMIDAZOLINE AND SEROTONIN RECEPTORS AND THE USE THEREOF
  申请人：Alla Chem, LLC.

  公开号：EP2236511A2

  公开（公告）日：2010-10-06

  The invention relates to novel ligands the broad spectrum of biological activity of which includes simultaneously α-adrenoceptors, dopamine receptors, histamine receptors, imidazoline receptors and serotonin receptors, among them serotonin 5-HT7 receptors, which are compounds of general formula 1 in the form of free bases, geometrical isomers, racemic mixtures or individual optical isomers, pharmaceutically acceptable salts and/or hydrates, wherein: R1 is a substituent of amino group, selected from hydrogen, optionally substituted C1-C4 alkyl, acyl, heterocyclyl, alkoxycarbonyl, substituted sulfonyl; R2 is a substituent of cyclic system, selected from hydrogen, halogen, optionally substituted C1-C4 alkyl, CF3, CN, alkoxy, alkoxycarbonyl, carboxyl, heterocyclyl or substituted sulfonyl; Ar is optionally substituted aryl not necessarily annalated with heterocyclyl, or optionally substituted aromatic heterocyclyl; W is optionally substituted (CH2)m group, optionally substituted CH=CH group, optionally substituted CH2-CH=CH group, C≡C group, SO2 group; n = 1, 2; m = 1, 2, 3; solid line accompanied by dotted line, i.e. (---) may represent single or double bond. The invention also relates to active ingredients, pharmaceutical compositions comprising the said ligands as active ingredients; to novel medicaments useful for treatment of diseases and conditions of central nervous system (CNS) of humans and warm-blooded animals.

  本发明涉及新型配体，其广泛的生物活性同时包括α-肾上腺素受体、多巴胺受体、组胺受体、咪唑啉受体和血清素受体，其中包括血清素5-HT7受体，这些配体是通式1化合物，其形式为游离碱、几何异构体、外消旋混合物或单个光学异构体、药学上可接受的盐和/或水合物、 其中R1 是氨基的取代基，选自氢、任选取代的 C1-C4 烷基、酰基、杂环基、烷氧羰基、取代的磺酰基； R2 是环状体系的取代基，选自氢、卤素、任选取代的 C1-C4 烷基、CF3、CN、烷氧基、烷氧羰基、羧基、杂环基或取代的磺酰基；Ar 是任选取代的芳基，不一定是环状杂环基，或任选取代的芳香族杂环基； W 是任选取代的 (CH2)m 基团、任选取代的 CH=CH 基团、任选取代的 CH2-CH=CH 基团、C≡C 基团、SO2 基团；n = 1、2；m = 1、2、3；实线伴有虚线，即.即（---）可代表单键或双键。 本发明还涉及活性成分、包含上述配体作为活性成分的药物组合物；涉及用于治疗人类和温血动物中枢神经系统（CNS）疾病和病症的新型药物。
• HARBERT C. A.; PLATTNER J. J.; WELCH W. M.; WEISSMAN A.; KOE B. K., J. MED. CHEM., 1980, 23, NO 6, 635-643
  作者：HARBERT C. A.、 PLATTNER J. J.、 WELCH W. M.、 WEISSMAN A.、 KOE B. K.

  DOI：——

  日期：——
• Substituted 2,3,4,5-Tetrahyrdo-1H-Pyrido[4,3-B]Indoles, Methods for the Production and Use Thereof
  申请人：Ivashchenko Andrey Alexandrovich

  公开号：US20100120792A1

  公开（公告）日：2010-05-13

  The invention relates to antagonists of serotonin 5-HT 6 receptors simultaneously regulating homeostasis of Ca +2 ions in cells, representing substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of the general formula 1, pharmaceutically acceptable salts and/or hydrate thereof. In the general formula 1: R 1 represents amino group substituent selected from optionally substituted C 1 -C 5 alkyl; R 2 , is one or more substituents selected from hydrogen, halogen, C 1 -C 3 alkyl, CF 3 , OCF 3 ; Ar is phenyl optionally substituted with halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, substituted amino group, or CF 3 ; or optionally substituted aromatic 6-membered heterocycle comprising 1-2 nitrogen atoms in the cycle; W represents ethylene group —CH 2 —CH 2 —, ethenyl group —CH═CH—, or ethynyl group —C≡C—. The invention also relates to the novel compounds selected from the compounds of the general formula 1, methods for their preparation, pharmaceutical compositions and methods of their use.
• LIGANDS OF ALPHA-ADRENOCEPTORS, DOPAMINE, HISTAMINE, IMIDAZOLINE AND SEROTONIN RECEPTORS AND THEIR USE
  申请人：Ivashchenko Andrey Alexandrovich

  公开号：US20110039825A1

  公开（公告）日：2011-02-17

  The invention relates to novel ligands the broad spectrum of biological activity of which includes simultaneously α-adrenoceptors, dopamine receptors, histamine receptors, imidazoline receptors and serotonin receptors, among them serotonin 5-HT 7 receptors, which are compounds of general formula 1 in the form of free bases, geometrical isomers, racemic mixtures or individual optical isomers, pharmaceutically acceptable salts and/or hydrates, wherein: R1 is a substituent of amino group, selected from hydrogen, optionally substituted C 1 -C 4 alkyl, acyl, heterocyclyl, alkoxycarbonyl, substituted sulfonyl; R2 is a substituent of cyclic system, selected from hydrogen, halogen, optionally substituted C 1 -C 4 alkyl, CF 3 , CN, alkoxy, alkoxycarbonyl, carboxyl, heterocyclyl or substituted sulfonyl; Ar is optionally substituted aryl not necessarily annalated with heterocyclyl, or optionally substituted aromatic heterocyclyl; W is optionally substituted (CH 2 ) m group, optionally substituted CH═CH group, optionally substituted CH 2 —CH═CH group, C≡C group, SO 2 group; n=1, 2; m=1, 2, 3; solid line accompanied by dotted line, i.e. may represent single or double bond. The invention also relates to active ingredients, pharmaceutical compositions comprising the said ligands as active ingredients; to novel medicaments useful for treatment of diseases and conditions of central nervous system (CNS) of humans and warm-blooded animals.