4-bromoisoquinoline-6-carboxylic acid | 1637280-23-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 4-bromoisoquinoline-6-carboxylic acid
• 英文别名: 4-Bromoisoquinoline-6-carboxylic acid
• CAS: 1637280-23-9
• 化学式: C₁₀H₆BrNO₂
• 分子量: 252.067
• InChiKey: XLWCQTRYIQADHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-bromoisoquinoline-6-carboxylic acid 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 、 N,N'-羰基二咪唑 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 2.5h， 生成 4-(4-(trifluoromethy1)pheny1)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
• 作为产物：
  描述：

  6-溴异喹啉 在 N-溴代丁二酰亚胺(NBS) 、 水 、 sodium acetate 、 palladium diacetate 、 溶剂黄146 、 三苯基膦 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 生成 4-bromoisoquinoline-6-carboxylic acid
  参考文献：
  名称：

  PYRIDO-FUSED BICYCLIC COMPOUNDS AS URAT1 INHIBITORS FOR TREATING HYPERURICEMIA

  摘要：

  公开号：

  EP3275867B1

文献信息

• [EN] NEW PHENYLPYRAZOLYLACETAMIDE COMPOUNDS AND DERIVATIVES AS CDK8/CDK19 INHIBITORS<br/>[FR] NOUVEAUX COMPOSÉS DE PHÉNYLPYRAZOLYLACÉTAMIDE ET DÉRIVÉS EN TANT QU'INHIBITEURS DE CDK8/CDK19
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2017202719A1

  公开（公告）日：2017-11-30

  The present invention encompasses compounds of formula (I) wherein the groups R2 to R5, A, X and q have the meanings given in the claims and specification, their use as inhibitors of CDK8/19, pharmaceutical compositions which contain compounds of this kind and their use as medicaments, especially as agents for treatment and/or prevention of oncological diseases.

  本发明涵盖了式(I)中R2至R5、A、X和q基团的化合物，其中这些基团的含义如权利要求和说明书中所述，它们作为CDK8/19的抑制剂的用途，含有这种化合物的药物组合物以及它们作为药物的用途，特别是作为治疗和/或预防肿瘤疾病的药剂。
• [EN] SUBSTITUTED MONO- AND POLYAZANAPHTHALENE DERIVATIVES AND THEIR USE<br/>[FR] DÉRIVÉS SUBSTITUÉS DE MONO- ET POLYAZANAPHTHALÈNE ET LEUR UTILISATION
  申请人：BASILEA PHARMACEUTICA AG

  公开号：WO2016128465A1

  公开（公告）日：2016-08-18

  Disclosed are compounds of formula (I) wherein A is CH or N, B is CR or N; and D is CR; R represents hydrogen, OH or NH2; R1 and R2, independently of each other, represent hydrogen, N(R3)2, halogen, cyano, nitro, R4-C1-C4alkyl, R4-C1-C4halogenoalkyl, OH, R4-C1-C4alkoxy, R4-C1-C4halogenoalkoxy, SH, R4-C1-C4alkythio, R4-C1-C4halogenoalkylthio; R3 represents, independently at each occurrence, hydrogen, R4-C1-C4alkyl or R4-C1-C4halogenoalkyl; R3a represents, independently at each occurrence, hydrogen or C1-C4 alkyl; R4 represents, independently at each occurrence, hydrogen, halogen, cyano, OH, SH, NH2, NH(CH3) or N(CH3)2; X represents a group of formula –E- or –E-F-, wherein E and F are different from each other and represent a group selected from –C(R3a)2-, -(C=O)-, -NR3a- and -O- and F is linked to Y, with the proviso that if X represents –E-F- one of E or F represents –C(R3a)2- or -(C=O)-; Y represents a group selected from C1-C6alkyl, mono- or bicyclic C3-C11cycloalkyl, which may be partially unsaturated, mono- or bicyclic 3 to 11-membered heterocycloalkyl, which may be partially unsaturated, a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, wherein said heterocycloalkyl group and said group comprising at least one heteroaryl cycle comprise one or more heteroatoms selected from nitrogen, oxygen and sulfur and said group Y is either unsubstituted or substituted by one or more substituents and comprises including its substituents one or more than one nitrogen atom having a lone electron pair; and Z represents a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, said heteroaryl cycle comprising one or more heteroatoms selected from nitrogen, oxygen and sulfur, which aryl or heteroaryl group is unsubstituted or substituted by one or more substituents; including tautomers of said compounds, mixtures of two tautomeric forms of said compounds, and pharmaceutically acceptable salts of said compounds, tautomers thereof or mixtures of two tautomeric forms thereof, preferably with the proviso that Y comprises one or more primary amino group -NH2, when X represents -(C=O)- or –(C=O)-NR3a-, wherein R3a represents hydrogen or C1-C4alkyl; which are useful for the treatment of proliferation disorders or diseases, such as cancer.

  公开的是以下式(I)的化合物，其中A为CH或N，B为CR或N；D为CR；R代表氢、OH或NH2；R1和R2彼此独立地代表氢、N(R3)2、卤素、氰基、硝基、R4-C1-C4烷基、R4-C1-C4卤代烷基、OH、R4-C1-C4烷氧基、R4-C1-C4卤代烷氧基、SH、R4-C1-C4硫代烷基、R4-C1-C4卤代硫代烷基；R3在每次出现时独立地代表氢、R4-C1-C4烷基或R4-C1-C4卤代烷基；R3a在每次出现时独立地代表氢或C1-C4烷基；R4在每次出现时独立地代表氢、卤素、氰基、OH、SH、NH2、NH(CH3)或N(CH3)2；X代表式-E-或-E-F-的基团，其中E和F彼此不同且代表从-C(R3a)2-、-(C=O)-、-NR3a-和-O中选择的基团，F与Y连接，但如果X代表-E-F-，则E或F中的一个代表-C(R3a)2-或-(C=O)-；Y代表从C1-C6烷基、单环或双环C3-C11环烷基（可能部分不饱和）、单环或双环3至11成员杂环烷基（可能部分不饱和）、包含至少一个芳基或杂芳基环的单环或双环基团，其中所述杂环烷基基团和包含至少一个杂芳基环的基团包含从氮、氧和硫中选择的一个或多个杂原子，所述基团Y未取代或被一个或多个取代基取代，包括其取代基中的一个或多个具有孤对电子的氮原子；Z代表包含至少一个芳基或杂芳基环的单环或双环基团，所述杂芳基环包含从氮、氧和硫中选择的一个或多个杂原子，该芳基或杂芳基基团未取代或被一个或多个取代基取代；包括所述化合物的互变异构体、所述化合物的两种互变异构体形式的混合物，以及所述化合物、其互变异构体或其两种互变异构体形式的药学上可接受的盐，其中Y包括一个或多个一级氨基-NH2，当X代表-(C=O)-或-(C=O)-NR3a-时，其中R3a代表氢或C1-C4烷基；这些化合物对于治疗增殖性疾病或疾病，如癌症，是有用的。
• 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。
• Phenylpyrazolylacetamide compounds and derivatives as CDK8/CDK19 inhibitors
  申请人：BOEHRINGER INGELHEIM INTERNATIONAL GMBH

  公开号：US11213520B2

  公开（公告）日：2022-01-04

  The present invention encompasses compounds of formula (I) wherein the groups R2 to R5, A, X and q have the meanings given in the claims and specification, their use as inhibitors of CDK8/19, pharmaceutical compositions which contain compounds of this kind and their use as medicaments, especially as agents for treatment and/or prevention of oncological diseases.

  本发明包括式（I）化合物（其中基团 R2 至 R5、A、X 和 q 具有权利要求书和说明书中给出的含义）、其作为 CDK8/19 抑制剂的用途、含有此类化合物的药物组合物以及其作为药物的用途，特别是作为治疗和/或预防肿瘤疾病的药物。
• [EN] CONDENSED RING DERIVATIVE, AND PREPARATION METHOD, INTERMEDIATE, PHARMACEUTICAL COMPOSITION AND USE THEREOF<br/>[FR] DÉRIVÉ CYCLIQUE CONDENSÉ, ET PROCÉDÉ DE PRÉPARATION, INTERMÉDIAIRE, COMPOSITION PHARMACEUTIQUE ET UTILISATION DE CELUI-CI<br/>[ZH] 稠环衍生物、其制备方法、中间体、药物组合物及应用
  申请人：SHANGHAI YINGLI PHARM CO LTD

  公开号：WO2016150255A1

  公开（公告）日：2016-09-29

  本发明公开了一种稠环衍生物、其制备方法、中间体、药物组合物及应用。本发明的稠环衍生物对URAT1具有明显抑制作用，能够有效缓解或治疗高尿酸血症等相关疾病。