1-[(3-fluoro-4-pyridinyl)propylamino]-3-methyl-1H-indol-5-yl heptylcarbamate

• 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: 1-[(3-fluoro-4-pyridinyl)propylamino]-3-methyl-1H-indol-5-yl heptylcarbamate
• 英文别名: Heptyl-carbamic acid 1-[(3-fluoro-pyridin-4-yl)-propyl-amino]-3-methyl-1H-indol-5-yl ester；[1-[(3-fluoropyridin-4-yl)-propylamino]-3-methylindol-5-yl] N-heptylcarbamate
• 化学式: C₂₅H₃₃FN₄O₂
• 分子量: 440.561
• InChiKey: PEQCQYWCZXAUJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-甲基-5-苯甲氧基-1H-吲哚 在 palladium on activated charcoal 氢氧化钾 、 氢气 、 sodium hydride 、 溶剂黄146 、 hydroxylamine-O-sulfonic acid 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 80.0 ℃ 、344.73 kPa 条件下， 反应 3.0h， 生成 1-[(3-fluoro-4-pyridinyl)propylamino]-3-methyl-1H-indol-5-yl heptylcarbamate
  参考文献：
  名称：

  Synthesis and preliminary structure-activity relationships of 1-[(3-fluoro-4-pyridinyl)amino]-3-methyl-1H-indol-5-yl methyl carbamate (P10358), a novel acetylcholinesterase inhibitor

  摘要：

  A series of carbamate analogs of besipirdine (HP 749) was synthesized as potential agents with enhanced cholinomimetic properties for the treatment of Alzheimer's disease. Compound 5a (P10358, 1-[3-fluoro-4-pyridinyl)amino]-3-methyl-1H-indol-5-yl methyl carbamate) emerged as a potent, reversible acetylcholinesterase inhibitor that significantly enhanced performance on oral or parenteral administration in earning and memory paradigms. (C) 1997, Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(96)00592-6

文献信息

• 1-(substituted pyridinylamino)-1H-indol-5-yl substituted carbamates
  申请人：Hoechst-Roussel Pharmaceuticals Inc.

  公开号：US05102891A1

  公开（公告）日：1992-04-07

  There are disclosed various compounds of the formula below, ##STR1## where n is 0 or 1; X is hydrogen, halogen, nitro, amino, trifluoromethyl, loweralkyl, or loweralkoxy; Y is hydrogen, halogen, nitro, amino, trifluoromethyl, loweralkyl, or loweralkoxy; R.sub.1 is hydrogen, loweralkyl, arylloweralkyl, loweralkenyl, loweralkynyl, loweralkanoyl, arylloweralkanoyl, heteroarylloweralkyl or heteroarylloweralkanoyl; R.sub.2 is hydrogen, loweralkyl, formyl or cyano; R.sub.3 is hydrogen or loweralkyl; R.sub.4 is loweralkyl, arylloweralkyl, cycloalkyl, aryl or heteroaryl; or alternatively, --NR.sub.3 R.sub.4 taken together constitutes ##STR2## R.sub.5 being hydrogen, loweralkyl, aryl, arylloweralkyl, heteroaryl or heteroarylloweralkyl, which compounds are useful for the treatment of various memory dysfunctions characterized by a cholinergic deficit such as Alzheimer's disease.

  下面公开了以下式的各种化合物，其中n为0或1；X为氢、卤素、硝基、氨基、三氟甲基、较低烷基或较低烷氧基；Y为氢、卤素、硝基、氨基、三氟甲基、较低烷基或较低烷氧基；R.sub.1为氢、较低烷基、芳基较低烷基、较低烯基、较低炔基、较低酰基、芳基较低酰基、杂芳基较低烷基或杂芳基较低酰基；R.sub.2为氢、较低烷基、甲酰基或氰基；R.sub.3为氢或较低烷基；R.sub.4为较低烷基、芳基较低烷基、环烷基、芳基或杂芳基；或者，--NR.sub.3 R.sub.4一起构成##STR2##，其中R.sub.5为氢、较低烷基、芳基、芳基较低烷基、杂芳基或杂芳基较低烷基，这些化合物对于治疗由胆碱缺乏引起的各种记忆功能障碍，如阿尔茨海默病，是有用的。
• 1-(Substituted pyridinylamino)-1H-indol-5-yl substituted carbamates, a process and intermediates for their preparation and their use as medicaments
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0468401A2

  公开（公告）日：1992-01-29

  There are disclosed various compounds of the formula below, where n is 0 or 1; X is hydrogen, halogen, nitro, amino, trifluoromethyl, loweralkyl, or loweralkoxy; Y is hydrogen, halogen, nitro, amino, trifluoromethyl, loweralkyl, or loweralkoxy; R1 is hydrogen, loweralkyl, arylloweralkyl, loweralkenyl, loweralkynyl, loweralkanoyl, arylloweralkanoyl, heteroarylloweralkyl or heteroarylloweralkanoyl; R2 is hydrogen, loweralkyl, formyl or cyano; R3 is hydrogen or loweralkyl; R4 is loweralkyl, arylloweralkyl, cycloalkyl, aryl or heteroaryl; or alternatively, -NR3R4 token together constitutes R5 being hydrogen, loweralkyl, aryl, arylloweralkyl, heteroaryl or heteroarylloweralkyl, which compounds are useful for the treatment of various memory dysfunctions characterized by a cholinergic deficit such as Alzheimer's disease.

  已公开了下式的各种化合物、 式中 n 是 0 或 1； X 是氢、卤素、硝基、氨基、三氟甲基、低级烷基或低级烷氧基； Y 是氢、卤素、硝基、氨基、三氟甲基、低级烷基或低级烷氧基； R1 是氢、低级烷基、芳基低级烷基、低级烯基、低级炔基、低级烷酰基、芳基低级烷酰基、杂芳基低级烷基或杂芳基低级烷酰基； R2 是氢、低级烷基、甲酰基或氰基； R3 是氢或低级烷基 R4 是低级烷基、芳低级烷基、环烷基、芳基或杂芳基；或者，-NR3R4 象征性地共同构成 R5 为氢、低级烷基、芳基、芳低级烷基、杂芳基或杂芳基低级烷基、 这些化合物可用于治疗以胆碱能不足为特征的各种记忆功能障碍，如阿尔茨海默病。
• 1-(Substituted pyridinylamino)-1H-indol-5-yl substituted carbamates, a process for their preparation and their use as medicaments
  申请人：HOECHST MARION ROUSSEL, Inc.

  公开号：EP0468401B1

  公开（公告）日：1998-09-16
• US5102891A
  申请人：——

  公开号：US5102891A

  公开（公告）日：1992-04-07
• Synthesis and preliminary structure-activity relationships of 1-[(3-fluoro-4-pyridinyl)amino]-3-methyl-1H-indol-5-yl methyl carbamate (P10358), a novel acetylcholinesterase inhibitor
  作者：Lawrence L. Martin、Larry Davis、Joseph T. Klein、Peter Nemoto、Gordon E. Olsen、Gina M. Bores、Fernando Camacho、Wayne W. Petko、Douglas K. Rush、David Selk、Craig P. Smith、Hugo M. Vargas、James T. Winslow、Richard C. Effland、David M. Fink

  DOI：10.1016/s0960-894x(96)00592-6

  日期：1997.1

  A series of carbamate analogs of besipirdine (HP 749) was synthesized as potential agents with enhanced cholinomimetic properties for the treatment of Alzheimer's disease. Compound 5a (P10358, 1-[3-fluoro-4-pyridinyl)amino]-3-methyl-1H-indol-5-yl methyl carbamate) emerged as a potent, reversible acetylcholinesterase inhibitor that significantly enhanced performance on oral or parenteral administration in earning and memory paradigms. (C) 1997, Elsevier Science Ltd.