5-Fluoro-3-{1-[6-(3,4-dihydro-1H-isoquinolin-2-yl)-6-oxohexan-1-yl]piperidin-4-yl}-1H-indole | 380612-01-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 5-Fluoro-3-{1-[6-(3,4-dihydro-1H-isoquinolin-2-yl)-6-oxohexan-1-yl]piperidin-4-yl}-1H-indole
• 英文别名: 1-(3,4-dihydro-1H-isoquinolin-2-yl)-6-[4-(5-fluoro-1H-indol-3-yl)piperidin-1-yl]hexan-1-one
• CAS: 380612-01-1
• 化学式: C₂₈H₃₄FN₃O
• 分子量: 447.596
• InChiKey: LUHSGVLLJASOCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  39.3
• 氢给体数：
  1
• 氢受体数：
  3

文献信息

• Indole derivatives useful for the treatment of CNS disorders
  申请人：H. Lundbeck A/S

  公开号：US20030191133A1

  公开（公告）日：2003-10-09

  The present invention relates to dopamine D 4 ligands having the general formula I 1 wherein (a) one of Y 1 and Y 2 is N, which is bound to Y 4 , and the other of Y 1 and Y 2 is CO, CS, SO, or SO 2 and Y 4 is CH 2 ; (b) one of Y 1 and Y 2 is N, which is bound to Y 4 , and the other of Y 1 and Y 2 is CH 2 and Y 4 is CO, CS, SO or SO 2 ; or (c) one of Y 1 and Y 2 is N, which is bound to Y 4 , and the other of Y 1 and Y 2 is CH 2 and Y 4 is CH 2 ; Y 3 is Z—CH 2 , CH 2 —Z or CH 2 CH 2 , and Z is O or S; provided that when Y 1 is N, Y 3 may not be Z—CH 2 ; W is a bond or an O, S, CO, CS, SO or SO 2 group; n is 0-5, m is 0-5 and m+n is 1-10; provided that when W is O or S, then n≧2 and m≧1; when W is CO, CS, SO or SO 2 , then n≧1 and m≧1; X is C, CH or N; provided that when X is C, the dotted line indicates a bond, and when X is N or CH, the dotted line is absent; R 1 -R 9 are independently selected from hydrogen, halogen, cyano, nitro, amino, hydroxy, C 1-6 -alkyl-amino, di-C 1-6 -alkyl-amino, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 1-6 alkoxy, C 1-6 -alkylthio, C 1-6 -alkyl substituted with hydroxy or thiol, C 3-8 -cycloalkyl, C 3-8 -cycloalkyl-C 1-6 -alkyl, acyl, thioacyl, aryl, trifluoromethyl, trifluoromethylsulfonyl, and C 1-6 alkylsulfonyl; R 10 is hydrogen, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 1-6 -alkyl substituted with hydroxy or thiol, C 3-8 -cycloalkyl, C 3-8 -cycloalkyl-C 1-6 -alkyl, aryl, aryl-C 1-6 -alkyl, acyl, thioacyl, C 1-6 -alkylsulfonyl, trifluoromethylsulfonyl or arylsulfonyl, or a pharmaceutically acceptable acid addition salt thereof. The compounds of the invention are potent dopamine D 4 receptor ligands.

  本发明涉及具有一般式I1的多巴胺D4配体，其中(a) Y1和Y2中的一个是与Y4结合的N，另一个是CO、CS、SO或SO2，而Y4是CH2；(b) Y1和Y2中的一个是与Y4结合的N，另一个是 ，而Y4是CO、CS、SO或SO2；或(c) Y1和Y2中的一个是与Y4结合的N，另一个是 ，而Y4是 ；Y3是Z— 、 —Z或 ，Z为O或S；但当Y1为N时，Y3不能是Z— ；W是键或O、S、CO、CS、SO或SO2基团；n为0-5，m为0-5，m+n为1-10；但当W为O或S时，n≥2且m≥1；当W为CO、CS、SO或SO2时，n≥1且m≥1；X为C、CH或N；但当X为C时，虚线表示键，当X为N或CH时，虚线不存在；R1-R9独立选择自氢、卤素、氰基、硝基、氨基、羟基、C1-6-烷基氨基、二-C1-6-烷基氨基、C1-6-烷基、C2-6-烯基、C2-6-炔基、C1-6-烷氧基、C1-6-烷基硫基、C1-6-烷基取代的羟基或硫醇基、C3-8-环烷基、C3-8-环烷基-C1-6-烷基、酰基、硫酰基、芳基、三氟甲基、三氟甲基磺酰基和C1-6-烷基磺酰基；R10为氢、C1-6-烷基、C2-6-烯基、C2-6-炔基、C1-6-烷基取代的羟基或硫醇基、C3-8-环烷基、C3-8-环烷基-C1-6-烷基、芳基、芳基-C1-6-烷基、酰基、硫酰基、C1-6-烷基磺酰基、三氟甲基磺酰基或芳基磺酰基，或其药学上可接受的酸加盐。本发明的化合物是有效的多巴胺D4受体配体。
• [EN] OXAZOLE DERIVATIVES AS HISTAMINE H3 RECEPTOR AGENTS, PREPARATION AND THERAPEUTIC USES<br/>[FR] DERIVES D'OXAZOLE EN TANT QU'AGENTS DE RECEPTEUR D'HISTAMINE H3, PREPARATION ET UTILISATIONS THERAPEUTIQUES
  申请人：LILLY CO ELI

  公开号：WO2006019833A1

  公开（公告）日：2006-02-23

  The present invention discloses novel aryl oxazole compounds of Formula I (I), or pharmaceutically acceptable salts thereof, which have histamine-H3 receptor antagonist or inverse agonist activity, as well as methods for preparing and using such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I as well as methods of using these compositions to treat obesity, cognitive deficiencies, narcolepsy, and other histamine H3 receptor-related diseases. Formula I (I) or a pharmaceutically acceptable salt thereof, wherein: m is independenlly at each occurrence 1, 2, or 3, Z independently represents carbon (substituted with hydrogen or the optional substituents indicated herein) or nitrogen, provided that when Z is nitrogen then R6 is not attached to Z; R1 and R2 are independently -(C1-C7) alkyl(optionally substituted with one to three halogens), or R1 and R2 and the nitrogen to which they are attached form an azetidinyl ring, a pyrrolidinyl ring, or a piperidinyl ring, wherein further the azetidinyl, pyrrolidinyl, or piperidinyl ring so formed may be optionally substituted one to three times with R5; R6 is independently at each occurrence -H, -halogen, or -CH3.

  本发明公开了具有组分I（I）的新型芳基噁唑化合物或其药学上可接受的盐，其具有组胺H3受体拮抗剂或逆向激动剂活性，以及制备和使用这些化合物的方法。在另一实施方案中，本发明公开了包括组分I化合物的药物组合物，以及使用这些组合物治疗肥胖、认知缺陷、嗜睡症和其他组胺H3受体相关疾病的方法。组分I（I）或其药学上可接受的盐，其中：m在每次出现时独立地为1、2或3，Z独立地表示碳（用氢或此处指示的可选取代基团取代）或氮，但当Z为氮时，R6不连接到Z；R1和R2独立地为-(C1-C7)烷基（可选地用一到三个卤素取代），或者R1和R2以及它们连接的氮形成氮杂环戊二烷环、吡咯环或哌啶环，进一步地，所形成的氮杂环戊二烷、吡咯环或哌啶环可以用R5取代一到三次；R6在每次出现时独立地为-H、-卤素或-CH3。
• Indole derivatives for the treatment of CNS disorders
  申请人：H. Lundbeck A/S

  公开号：EP1468996A1

  公开（公告）日：2004-10-20

  The present invention relates to dopamine D4 ligands having the general formula I wherein (a) one of Y1 and Y2 is N, which is bound to Y4, and the other of Y1 and Y2 is CO, CS, SO, or SO2 and Y4 is is CH2; (b) one of Y1 and Y2 is N, which is bound to Y4, and the other of Y1 and Y2 is CH2 and Y4is CO, CS, SO or SO2; or (c) one of Y1 and Y2 is N, which is bound to Y4, and the other of Y1 and Y2 is CH2 and Y4 is CH2; Y3 is Z-CH2, CH2-Z or CH2CH2, and Z is O or S; provided that when Y1 is N, Y3 may not Z-CH2; W is a bond or an O, S, CO, CS, SO or SO2 group; n is 0-5, m is 0-5 and m + n is 1-10; provided that when W is O, or S, then n ≥ 2 and m ≥ 1; when W is CO, CS, SO or SO2, then n ≥ 1 and m ≥ 1; X is C, CH or N; provided that when X is C, the dotted line indicates a bond, and when X is N or CH, the dotted line is not a bond; R1 -R9 are independently selected from hydrogen, halogen, cyano, nitro, amino, hydroxy, C1-6-alkyl-amino, di-C1-6-alkyl-amino, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C1-6 alkoxy, C1-6-alkylthio, C1-6-alkyl substituted with hydroxy or thiol, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, acyl, thioacyl, aryl, trifluoromethyl, trifluoromethylsulfonyl, and C1-6 alkylsulfonyl; R10 is hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C1-6-alkyl substituted with hydroxy or thiol, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, aryl, aryl-C1-6-alkyl, acyl, thioacyl, C1-6-alkylsulfonyl, trifluoromethylsulfonyl or arylsulfonyl, or a pharmaceutically acceptable acid addition salt thereof. The compounds of the invention are potent dopamine D4 receptor ligands.

  本发明涉及具有通式 I 的多巴胺 D4 配体 其中 (a) Y1 和 Y2 中的一个是与 Y4 结合的 N，Y1 和 Y2 中的另一个是 CO、CS、SO 或 SO2，Y4 是 CH2； (b) Y1 和 Y2 中的一个是与 Y4 结合的 N，Y1 和 Y2 中的另一个是 ，Y4 是 CO、CS、SO 或 SO2；或 (c) Y1 和 Y2 中的一个是与 Y4 结合的 N，Y1 和 Y2 中的另一个是 ，而 Y4 是 ； Y3 是 Z- 、 -Z 或 ，且 Z 是 O 或 S；但当 Y1 是 N 时，Y3 不得是 Z- ； W 是键或 O、S、CO、CS、SO 或 SO2 基团； n为0-5，m为0-5，m+n为1-10；但当W为O或S时，则n≥2，m≥1；当W为CO、CS、SO或SO2时，则n≥1，m≥1； X 是 C、CH 或 N；但当 X 是 C 时，虚线表示键，当 X 是 N 或 CH 时，虚线不是键； C1-6-烷硫基、被羟基或硫醇取代的 C1-6- 烷基、C3-8-环烷基、C3-8-环烷基-C1-6-烷基、酰基、硫酰基、芳基、三氟甲基、三氟甲基磺酰基和 C1-6 烷基磺酰基； R10 是氢、C1-6-烷基、C2-6-烯基、C2-6-炔基、被羟基或硫醇取代的 C1-6 烷基、C3-8-环烷基、C3-8-环烷基-C1-6-烷基、芳基、芳基-C1-6-烷基、酰基、硫酰基、C1-6-烷基磺酰基、三氟甲基磺酰基或芳基磺酰基，或其药学上可接受的酸加成盐。 本发明的化合物是强效多巴胺 D4 受体配体。
• INDOLE DERIVATIVES USEFUL FOR THE TREATMENT OF CNS DISORDERS
  申请人：H. LUNDBECK A/S

  公开号：EP1294710B1

  公开（公告）日：2005-06-08
• OXAZOLE DERIVATIVES AS HISTAMINE H3 RECEPTOR AGENTS, PREPARATION AND THERAPEUTIC USES
  申请人：ELI LILLY AND COMPANY

  公开号：EP1786790A1

  公开（公告）日：2007-05-23