methyl 7-bromo-5-cyano-1H-indole-2-carboxylate

• 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: methyl 7-bromo-5-cyano-1H-indole-2-carboxylate
• 化学式: C₁₁H₇BrN₂O₂
• 分子量: 279.093
• InChiKey: OVIJARQHURBSOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.59
• 重原子数：
  16.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  65.88
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  7-bromo-5-cyano-2-diethoxymethylindole-1-carboxylic acid tert-butyl ester 在 盐酸 、 sodium cyanide 、 manganese(IV) oxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 22.25h， 生成 methyl 7-bromo-5-cyano-1H-indole-2-carboxylate
  参考文献：
  名称：

  [EN] PIPERAZINO[1,2-A]INDOL-1-ONES AND [1,4]DIAZEPINO[1,2-A]INDOL-1-ONE
  [FR] PIPÉRAZINO[1,2-A]INDOL-1-ONES ET [1,4]DIAZÉPINO[1,2-A]INDOL-1-ONE

  摘要：

  本发明涉及一般式I的化合物，其中R1是卤素、较低的烷基、较低的烷氧基、由卤素取代的较低的烷基、由卤素取代的较低的烷氧基或氰基；R2是氢、三氟甲基或较低的烷基；R3是氢、较低的烷基、较低的烯基、较低的炔基、杂环烷基、由氰基取代的较低的烷基、氰基、由卤素取代的苄基、2-氧-6-氮杂螺[3.3]庚-6-基或由卤素取代的较低的烷氧基；X是-CH2-或-CH2-CH2-；或是其对应的对映体和/或光学异构体的药用可接受的酸盐，或是一个外消旋混合物。这些化合物可用于治疗精神分裂症、强迫性人格障碍、重性抑郁症、躁郁症、焦虑障碍、正常衰老、癫痫、视网膜退化、创伤性脑损伤、脊髓损伤、创伤后应激障碍、恐慌障碍、帕金森病、痴呆症、阿尔茨海默病、轻度认知障碍、化疗引起的认知功能障碍、唐氏综合征、自闭症谱系障碍、听力丧失、耳鸣、脊髓小脑共济失调、肌萎缩侧索硬化、多发性硬化、亨廷顿病、中风、放射治疗、慢性压力、对神经活性药物的滥用，如酒精、阿片类药物、甲基苯丙胺、芬太尼和可卡因。

  公开号：

  WO2014161801A1

文献信息

• [EN] PIPERAZINO[1,2-A]INDOL-1-ONES AND [1,4]DIAZEPINO[1,2-A]INDOL-1-ONE<br/>[FR] PIPÉRAZINO[1,2-A]INDOL-1-ONES ET [1,4]DIAZÉPINO[1,2-A]INDOL-1-ONE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014161801A1

  公开（公告）日：2014-10-09

  The present invention relates to compounds of general formula I wherein R1 is halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen or cyano; R2 is hydrogen, CF3 or lower alkyl; R3 is hydrogen, lower alkyl, lower alkenyl, lower alkinyl, heterocycloalkyl, lower alkyl substitueted by cyano, cyano, benzyl substituted by halogen, 2-oxa-6-aza-spiro[3.3]hept-6-yl or is lower alkoxy substituted by halogen; X is -CH2- or -CH2-CH2-; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof. The compounds may be used for the treatment of schizophrenia, obsessive-compulsive personality disorder, major depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, mild cognitive impairment, chemotherapy-induced cognitive dysfunction, Down syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of neuro-active drugs, such as alcohol, opiates, methamphetamine, phencyclidine and cocaine.

  本发明涉及一般式I的化合物，其中R1是卤素、较低的烷基、较低的烷氧基、由卤素取代的较低的烷基、由卤素取代的较低的烷氧基或氰基；R2是氢、三氟甲基或较低的烷基；R3是氢、较低的烷基、较低的烯基、较低的炔基、杂环烷基、由氰基取代的较低的烷基、氰基、由卤素取代的苄基、2-氧-6-氮杂螺[3.3]庚-6-基或由卤素取代的较低的烷氧基；X是-CH2-或-CH2-CH2-；或是其对应的对映体和/或光学异构体的药用可接受的酸盐，或是一个外消旋混合物。这些化合物可用于治疗精神分裂症、强迫性人格障碍、重性抑郁症、躁郁症、焦虑障碍、正常衰老、癫痫、视网膜退化、创伤性脑损伤、脊髓损伤、创伤后应激障碍、恐慌障碍、帕金森病、痴呆症、阿尔茨海默病、轻度认知障碍、化疗引起的认知功能障碍、唐氏综合征、自闭症谱系障碍、听力丧失、耳鸣、脊髓小脑共济失调、肌萎缩侧索硬化、多发性硬化、亨廷顿病、中风、放射治疗、慢性压力、对神经活性药物的滥用，如酒精、阿片类药物、甲基苯丙胺、芬太尼和可卡因。
• INDOLE-CARBOXAMIDES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20160185721A1

  公开（公告）日：2016-06-30

  The present invention relates to compounds of general formula wherein R 1 is aryl or heteroaryl, which are optionally substituted by one, two or three substituents, selected from lower alkyl, halogen, lower alkyl substituted by halogen, hydroxyl, lower alkoxy, lower alkoxy substituted by halogen, cyano or nitro; R 2 is halogen, lower alkyl or cyano; R 3 is hydrogen or lower alkyl; R 4 is hydrogen or lower alkyl; R 5 , R 6 are hydrogen, lower alkyl, or may form together with the N-atom to which they are attached a heterocycloalkyl ring; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof. The compounds may be used for the treatment of schizophrenia, obsessive-compulsive personality disorder, major depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, cognitive impairment, chemotherapy-induced cognitive dysfunction (“chemobrain”), Down syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, and disturbances due to radiation therapy, chronic stress, or abuse of neuro-active drugs, selected from alcohol, opiates, methamphetamine, phencyclidine and cocaine.

  本发明涉及一般式化合物，其中R1为芳基或杂环芳基，可以选择性地由一、二或三个取代基取代，所述取代基选自较低的烷基、卤素、被卤素取代的较低烷基、羟基、较低的烷氧基、被卤素取代的较低烷氧基、氰基或硝基；R2为卤素、较低的烷基或氰基；R3为氢或较低的烷基；R4为氢或较低的烷基；R5，R6为氢、较低的烷基，或者可以与它们附着的N原子一起形成杂环脂肪环；或者是其相应的对映体和/或光学异构体的药学上可接受的酸加成盐或外消旋混合物。这些化合物可用于治疗精神分裂症、强迫性人格障碍、重度抑郁症、躁郁症、焦虑症、正常衰老、癫痫、视网膜退化、创伤性脑损伤、脊髓损伤、创伤后应激障碍、惊恐症、帕金森病、痴呆、阿尔茨海默病、认知障碍、化疗导致的认知功能障碍（“化疗脑”）、唐氏综合征、自闭症谱系障碍、听力损失、耳鸣、脊髓小脑性共济失调、肌萎缩侧索硬化症、多发性硬化症、亨廷顿病、中风以及由放射治疗、慢性压力或神经活性药物（如酒精、鸦片类、甲基苯丙胺、苯环利定和可卡因）滥用引起的障碍。
• PIPERAZINO[1,2-A]INDOL-1-ONES AND [1,4]DIAZEPINO[1,2-A]INDOL-1-ONE
  申请人：Hoffmann-La Roche Inc.

  公开号：US20150246922A1

  公开（公告）日：2015-09-03

  The present invention relates to compounds of general formula I or pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , X, R and n are as defined herein. The compounds may be used for the treatment of schizophrenia, obsessive-compulsive personality disorder, major depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, mild cognitive impairment, chemotherapy-induced cognitive dysfunction, Down syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of neuro-active drugs, such as alcohol, opiates, methamphetamine, phencyclidine and cocaine.

  本发明涉及公式I或其药学上可接受的盐的化合物，其中R1、R2、R3、X、R和n的定义如本文所述。这些化合物可用于治疗精神分裂症、强迫症人格障碍、重度抑郁症、双相障碍、焦虑症、正常衰老、癫痫、视网膜退化、创伤性脑损伤、脊髓损伤、创伤后应激障碍、恐慌障碍、帕金森病、痴呆症、阿尔茨海默病、轻度认知障碍、化疗引起的认知功能障碍、唐氏综合症、自闭症谱系障碍、听力损失、耳鸣、脊髓小脑性共济失调、肌萎缩性侧索硬化症、多发性硬化症、亨廷顿病、中风、放射治疗、慢性压力、神经活性药物滥用，如酒精、鸦片类、甲基苯丙胺、苯环利定和可卡因。
• Piperazino[1,2-a]indol-1-ones and [1,4]diazepino[1,2-a]indol-1-one
  申请人：Hoffmann-La Roche Inc.

  公开号：US09284321B2

  公开（公告）日：2016-03-15

  The present invention relates to compounds of general formula I or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, X, R and n are as defined herein. The compounds may be used for the treatment of schizophrenia, obsessive-compulsive personality disorder, major depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, mild cognitive impairment, chemotherapy-induced cognitive dysfunction, Down syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of neuro-active drugs, such as alcohol, opiates, methamphetamine, phencyclidine and cocaine.

  本发明涉及一般式I的化合物或其药学上可接受的盐，其中R1、R2、R3、X、R和n的定义如本文所述。这些化合物可用于治疗精神分裂症、强迫症人格障碍、重度抑郁症、双相障碍、焦虑症、正常衰老、癫痫、视网膜退化、创伤性脑损伤、脊髓损伤、创伤后应激障碍、惊恐障碍、帕金森病、痴呆症、阿尔茨海默病、轻度认知障碍、化疗引起的认知功能障碍、唐氏综合症、自闭症谱系障碍、听力损失、耳鸣、脊髓小脑性共济失调、肌萎缩侧索硬化症、多发性硬化症、亨廷顿病、中风、放射治疗、慢性压力、对神经活性药物的滥用，如酒精、鸦片类、甲基苯丙胺、苯环利定和可卡因等。
• Piperazino[1,2-a]indol-1-ones and [1,4]diazepino[1,2-a]indol-one
  申请人：Hoffmann-La Roche Inc.

  公开号：US20160016963A1

  公开（公告）日：2016-01-21

  The present invention relates to compounds of general formula I wherein R 1 is halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen or cyano; R 2 is hydrogen, CF 3 or lower alkyl; R 3 is hydrogen, lower alkyl, lower alkenyl, lower alkinyl, heterocycloalkyl, lower alkyl substituted by cyano, cyano, benzyl substituted by halogen, 2-oxa-6-aza-spiro[3.3]hept-6-yl or is lower alkoxy substituted by halogen; X is —CH 2 — or —CH 2 —CH 2 —; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof. The compounds may be used for the treatment of schizophrenia, obsessive-compulsive personality disorder, major depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, mild cognitive impairment, chemotherapy-induced cognitive dysfunction, Down syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of neuro-active drugs, such as alcohol, opiates, methamphetamine, phencyclidine and cocaine.

  本发明涉及一般式I的化合物，其中R1为卤素，低碳基，低烷氧基，低碳基取代的卤素，低烷氧基取代的卤素或氰基; R2为氢，CF3或低碳基; R3为氢，低碳基，低烯基，低炔基，杂环烷基，低碳基取代的氰基，氰基，卤素取代的苄基，2-氧杂-6-氮-螺[3.3]庚-6-基或低烷氧基取代的卤素; X为-CH2-或-CH2-CH2-; 或其对应的对映体和/或光学异构体的药学上可接受的酸加合物或外消旋混合物。这些化合物可用于治疗精神分裂症、强迫性人格障碍、重度抑郁症、双相障碍、焦虑症、正常衰老、癫痫、视网膜退行性疾病、创伤性脑损伤、脊髓损伤、创伤后应激障碍、惊恐障碍、帕金森病、痴呆、阿尔茨海默病、轻度认知障碍、化疗引起的认知功能障碍、唐氏综合症、自闭症谱系障碍、听力损失、耳鸣、脊髓小脑性共济失调、肌萎缩性侧索硬化症、多发性硬化症、亨廷顿病、中风、放射治疗、慢性压力、神经活性药物滥用，如酒精、鸦片类、甲基苯丙胺、苯环利定和可卡因。