4-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)isoquinoline-6-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)isoquinoline-6-carboxamide
• 英文别名: 4-(4-Chlorophenyl)-N-(2,2,2-trifluoroethyl)isoquinoline-6-carboxamide
• 化学式: C₁₈H₁₂ClF₃N₂O
• 分子量: 364.754
• InChiKey: SWHIAVHTFRACGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-异喹啉甲酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 N-溴代丁二酰亚胺(NBS) 、 caesium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.08h， 生成 4-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)isoquinoline-6-carboxamide
  参考文献：
  名称：

  [EN] NEUROGENESIS-STIMULATING ISOQUINOLINE DERIVATIVES
  [FR] DÉRIVÉS D'ISOQUINOLINE DE STIMULATION DE LA NEUROGENÈSE

  摘要：

  本发明涉及使用一般式（I）的化合物，其中R1为苯基或吡啶基，可选择地被卤素、氰基或被卤素取代的较低烷基取代，或为二氢吡喃-4-基；R2为氢或较低烷基；R3为-(CHR)n-苯基，可选择地被较低烷氧基或S（O）2-较低烷基取代，或为杂环烷基，可选择地被=O和较低烷基取代，或为-(CH2)n-五元或六元杂环芳基，可选择地被较低烷基取代，或为氢、较低烷基、被卤素取代的较低烷基、被羟基取代的较低烷基、-NR-S（O）2-较低烷基、-(CH2)n-环烷基或-(CH2)n-S（O）2-较低烷基；或R2和R3与它们连接的N原子共同形成一个杂环烷基环，选自由1,1-二氧化硫代噻吩基、吗啉基或吡咯啉基，可选择地被羟基取代；R为氢或较低烷基；n为0、1或2；或是药学上可接受的酸盐，或为外消旋混合物或其对映体和/或光学异构体，用于治疗精神分裂症、强迫性人格障碍、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、惊恐障碍、帕金森病、痴呆症、阿尔茨海默病、轻度认知障碍、化疗诱导的认知功能障碍（“化疗脑”）、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、肌萎缩性侧索硬化、多发性硬化症、亨廷顿病、中风，以及由放射治疗、慢性应激、视神经病变或黄斑变性、或滥用神经活性药物（如酒精、阿片类药物、甲基苯丙胺、芬太尼或可卡因）引起的干扰。

  公开号：

  WO2014177596A1

文献信息

• ISOQUINOLINE DERIVATIVES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20160046583A1

  公开（公告）日：2016-02-18

  The present invention relates to the use of compounds of general formula wherein R 1 is phenyl or pyridinyl, which are optionally substituted by halogen, cyano or lower alkyl substituted by halogen, or is dihydro-pyran-4-yl; R 2 is hydrogen or lower alkyl; R 3 is —(CHR) n -phenyl, optionally substituted by lower alkoxy or S(O) 2 -lower alkyl, or is heterocycloalkyl, optionally substituted by ═O and lower alkyl, or is —(CH 2 ) n -five or six membered heteroaryl, optionally substituted by lower alkyl, or is hydrogen, lower alkyl, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, —NR—S(O) 2 -lower alkyl, —(CH 2 ) n -cycloalkyl or —(CH 2 ) n —S(O) 2 -lower alkyl; or R 2 and R 3 form together with the N-atom to which they are attached a heterocycloalkyl ring, selected from the group consisting of 1,1-dioxo-thiomorpholinyl, morpholinyl, or pyrrolidinyl, optionally substituted by hydroxyl; R is hydrogen or lower alkyl; n is 0, 1 or 2; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof, for the treatment of schizophrenia, obsessive-compulsive personality disorder, 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 (“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, optic neuropathy or macular degeneration, or abuse of neuro-active drugs, such as alcohol, opiates, methamphetamine, phencyclidine or cocaine.

  本发明涉及使用通式化合物，其中R1是苯基或吡啶基，可以通过卤素、氰基或受卤素取代的较低烷基取代，或者是二氢吡喃-4-基；R2是氢或较低烷基；R3是-（CHR）n-苯基，可以通过较低烷氧基或S（O）2-较低烷基取代，或者是杂环脂肪基，可以通过═O和较低烷基取代，或者是-（CH2）n-五或六元杂环芳基，可以通过较低烷基取代，或者是氢、较低烷基、受卤素取代的较低烷基、羟基取代的较低烷基、-NR-S（O）2-较低烷基、-（CH2）n-环烷基或-（CH2）n-S（O）2-较低烷基；或R2和R3与它们连接的N原子一起形成一个杂环脂肪基环，选择自由基团1,1-二氧代硫代吗啉基、吗啉基或吡咯烷基，可以通过羟基取代；R是氢或较低烷基；n是0、1或2；或其药学上可接受的酸盐、外消旋混合物或其对应的对映异构体，用于治疗精神分裂症、强迫性人格障碍、抑郁症、双相障碍、焦虑障碍、正常老化、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、化疗诱导的认知功能障碍（“化疗脑”）、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、中风以及由放射治疗、慢性应激、视神经病变或黄斑变性、神经活性药物滥用，如酒精、鸦片类、甲基苯丙胺、苯环利定或可卡因引起的干扰。
• NEUROGENESIS-STIMULATING ISOQUINOLINE DERIVATIVES
  申请人：F.Hoffmann-La Roche AG

  公开号：EP2991635A1

  公开（公告）日：2016-03-09
• US9586903B2
  申请人：——

  公开号：US9586903B2

  公开（公告）日：2017-03-07
• [EN] NEUROGENESIS-STIMULATING ISOQUINOLINE DERIVATIVES<br/>[FR] DÉRIVÉS D'ISOQUINOLINE DE STIMULATION DE LA NEUROGENÈSE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014177596A1

  公开（公告）日：2014-11-06

  The present invention relates to the use of compounds of general formula (I), wherein R1 is phenyl or pyridinyl, which are optionally substituted by halogen, cyano or lower alkyl substituted by halogen, or is dihydro-pyran-4-yl; R2 is hydrogen or lower alkyl; R3 is -(CHR)n-phenyl, optionally substituted by lower alkoxy or S(O)2-lower alkyl, or is heterocycloalkyl, optionally substituted by =O and lower alkyl, or is -(CH2)n-five or six membered heteroaryl, optionally sunbstituted by lower alkyl, or is hydrogen, lower alkyl, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, -NR-S(O)2-lower alkyl, -(CH2)n-cycloalkyl or -(CH2)n-S(O)2-lower alkyl; or R2 and R3 form together with the N-atom to which they are attached a heterocycloalkyl ring, selected from the group consisting of 1,1-dioxo-thiomorpholinyl, morpholinyl, or pyrrolidinyl, optionally substituted by hydroxyl; R is hydrogen or lower alkyl; n is 0, 1 or 2; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof, for the treatment of schizophrenia, obsessive-compulsive personality disorder, 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 ("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, optic neuropathy or macular degeneration, or abuse of neuro-active drugs, such as alcohol, opiates, methamphetamine, phencyclidine or cocaine.

  本发明涉及使用一般式（I）的化合物，其中R1为苯基或吡啶基，可选择地被卤素、氰基或被卤素取代的较低烷基取代，或为二氢吡喃-4-基；R2为氢或较低烷基；R3为-(CHR)n-苯基，可选择地被较低烷氧基或S（O）2-较低烷基取代，或为杂环烷基，可选择地被=O和较低烷基取代，或为-(CH2)n-五元或六元杂环芳基，可选择地被较低烷基取代，或为氢、较低烷基、被卤素取代的较低烷基、被羟基取代的较低烷基、-NR-S（O）2-较低烷基、-(CH2)n-环烷基或-(CH2)n-S（O）2-较低烷基；或R2和R3与它们连接的N原子共同形成一个杂环烷基环，选自由1,1-二氧化硫代噻吩基、吗啉基或吡咯啉基，可选择地被羟基取代；R为氢或较低烷基；n为0、1或2；或是药学上可接受的酸盐，或为外消旋混合物或其对映体和/或光学异构体，用于治疗精神分裂症、强迫性人格障碍、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、惊恐障碍、帕金森病、痴呆症、阿尔茨海默病、轻度认知障碍、化疗诱导的认知功能障碍（“化疗脑”）、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、肌萎缩性侧索硬化、多发性硬化症、亨廷顿病、中风，以及由放射治疗、慢性应激、视神经病变或黄斑变性、或滥用神经活性药物（如酒精、阿片类药物、甲基苯丙胺、芬太尼或可卡因）引起的干扰。