7-amino-4,4-dimethyl-2H,4H-isoquinoline-1,3-dione | 14576-22-8

• 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: 7-amino-4,4-dimethyl-2H,4H-isoquinoline-1,3-dione
• 英文别名: 7-amino-4,4-dimethylisoquinoline-1,3-dione；7-amino-4,4-dimethyl-4H-isoquinoline-1,3-dione；7-amino-4,4-dimethylisoquinoline-1,3(2H,4H)-dione；4,4-Dimethyl-7-amino-homophthalimid
• CAS: 14576-22-8
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: SFEHKRXHTPYTHM-UHFFFAOYSA-N

物化性质

• 熔点：
  176-179 °C(Solv: methanol (67-56-1))
• 沸点：
  444.1±45.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  72.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-amino-4,4-dimethyl-2H,4H-isoquinoline-1,3-dione 在 platinum(IV) oxide sodium tetrahydroborate 、 氢气 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， -20.0~70.0 ℃ 、344.75 kPa 条件下， 反应 21.25h， 生成 2-(2,6-Dichloro-phenylamino)-6,6-dimethyl-1,6,7,8-tetrahydro-imidazo[4,5-h]isoquinolin-9-one
  参考文献：
  名称：

  Discovery of 2-Phenylamino-imidazo[4,5-h]isoquinolin-9-ones:  A New Class of Inhibitors of Lck Kinase

  摘要：

  An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to understand how 1 binds to a related kinase, lick. These results suggested that removing the gem-dimethyl group and flattening the ring would enhance activity. This was realized by converting 1 to the imidazo[4,5-h]isoquinolin-9-one (20), resulting in an 18-fold improvement in potency against lck and a 50-fold increase in potency in a cellular assay.

  DOI：

  10.1021/jm020113o
• 作为产物：
  描述：

  4,4-二甲基-7-硝基异喹啉-1,3-二酮 在 10percent Pd/C 氢气 作用下， 以 甲醇 为溶剂， 反应 1.5h， 以98%的产率得到7-amino-4,4-dimethyl-2H,4H-isoquinoline-1,3-dione
  参考文献：
  名称：

  Discovery of 2-Phenylamino-imidazo[4,5-h]isoquinolin-9-ones:  A New Class of Inhibitors of Lck Kinase

  摘要：

  An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to understand how 1 binds to a related kinase, lick. These results suggested that removing the gem-dimethyl group and flattening the ring would enhance activity. This was realized by converting 1 to the imidazo[4,5-h]isoquinolin-9-one (20), resulting in an 18-fold improvement in potency against lck and a 50-fold increase in potency in a cellular assay.

  DOI：

  10.1021/jm020113o

文献信息

• Bicycloheteroarylamine compounds as ion channel ligands and uses thereof
  申请人：Kelly G. Michael

  公开号：US20050277643A1

  公开（公告）日：2005-12-15

  Amine compounds are disclosed that have a formula represented by the following: The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, traumatic injury, and others.

  抗氨化合物的公开披露，其化学式如下所示： 这些化合物可以制备成药物组合物，并可用于预防和治疗包括人类在内的哺乳动物的各种疾病，例如疼痛、炎症、创伤等。
• [EN] BICYCLOHETEROARYLAMINE COMPOUNDS AS ION CHANNEL LIGANDS AND USES THEREOF<br/>[FR] COMPOSES BICYCLOHETEROARYLAMINE COMME LIGANDS DE CANAUX IONIQUES ET UTILISATIONS DESDITS COMPOSES
  申请人：RENOVIS INC

  公开号：WO2005066171A1

  公开（公告）日：2005-07-21

  Amine compounds are disclosed that have a formula represented by the following: The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, traumatic injury, and others.

  抗氨化合物的公开披露，其化学式如下所示：这些化合物可以制备成药物组合物，并可用于预防和治疗包括人类在内的哺乳动物的各种疾病，例如疼痛、炎症、创伤等。
• Heterocyclic compounds useful as inhibitors of tyrosine kinases
  申请人：——

  公开号：US20020016460A1

  公开（公告）日：2002-02-07

  Disclosed are novel compounds of formula (I): 1 wherein Ar 1 , R a , R 4 , R 5 , X and Y are defined below, which are useful as inhibitors of certain protein tyrosine kinases and are thus useful for treating diseases associated with such kinases, for example, diseases resulting from inappropriate cell proliferation, which include autoimmune diseases, chronic inflammatory diseases, allergic diseases, transplant rejection and cancer, as well as conditions resulting from cerebral ischemia, such as stroke. Also disclosed are processes for preparing these compounds, novel intermediates useful in these processes and compositions comprising compounds of the formula (I).

  揭示了式（I）的新化合物：其中Ar1、Ra、R4、R5、X和Y的定义如下，这些化合物可用作某些蛋白酪氨酸激酶的抑制剂，因此可用于治疗与这些激酶相关的疾病，例如由于细胞不当增殖而导致的疾病，包括自身免疫疾病、慢性炎症性疾病、过敏疾病、移植排斥和癌症，以及由脑缺血引起的疾病，如中风。还披露了制备这些化合物的方法，这些方法中有用的新中间体以及包含式（I）化合物的组合物。
• Isoquinolinedione derivatives, pharmaceutical compositions and methods
  申请人：Boehringer Mannheim GmbH

  公开号：US04824835A1

  公开（公告）日：1989-04-25

  The present invention provides isoquinolinedione derivatives of the general formula: ##STR1## wherein R.sub.1 is a hydrogen atom or an alkyl, alkenyl or cycloalkyl radical which is optionally interrupted by a heteroatom or by a heteroatom substituted with an alkyl radical, R.sub.2 is a hydrogen atom or an alkyl or alkenyl radical, or together with R.sub.1, represents a cycloalkylene, alkylidene or cycloalkylidene radical which is optionally interrupted by a heteroatom or by a heteroatom substituted by an alkyl radical and R.sub.3 is a radical of the general formula: ##STR2## which can be in the 5- 6-, 7- or 8-position of the isoquinoline-1,3-dione and in which R.sub.4 and R.sub.5, which can be the same or different, are hydrogen atoms or alkyl, trihaloalkyl, cycloalkyl, cycloalkenyl, dealkylaminoalkyl, alkoxycarbonylalkyl, alkylcarbonyl, aryl or heterayl radicals and X is an oxygen or sulphur atom or a radical of the general formula .dbd.N--R.sub.6, in which R.sub.6 is a hydrogen atom, a cyano group of an alkyl radical; and the physiologically acceptable salts thereof. The present invention also provides processes for the preparation of these compounds and pharmaceutical compositions containing them. These new compounds have a blood pressure lowering effect and/or influence thrombocyte aggregation, improve the microcirculation, and exert a positive intropic effect, thus having therapeutic and prophylactic effects.

  本发明提供了一般式为：##STR1##的异喹啉二酮衍生物，其中R.sub.1是氢原子或烷基、烯基或环烷基基团，可以由一个杂原子或由一个被烷基基团取代的杂原子中断；R.sub.2是氢原子或烷基或烯基基团，或者与R.sub.1一起代表一个可以由一个杂原子或由一个被烷基基团取代的杂原子中断的环烷烃基、烷基亚甲基或环烷基亚甲基基团；R.sub.3是一般式为：##STR2##的基团，可以在异喹啉-1,3-二酮的5-、6-、7-或8-位上，其中R.sub.4和R.sub.5可以相同也可以不同，是氢原子或烷基、三卤代烷基、环烷基、环烯基、去烷基氨基烷基、烷氧羰基烷基、烷基羰基、芳基或杂芳基基团，X是氧原子或硫原子或一般式.dbd.N--R.sub.6的基团，其中R.sub.6是氢原子、氰基或烷基基团；以及其生理上可接受的盐。本发明还提供了制备这些化合物的方法和含有它们的药物组合物。这些新化合物具有降低血压和/或影响血小板聚集、改善微循环、产生正性肌力作用的效果，因此具有治疗和预防作用。
• Isochinolindione, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
  申请人：BOEHRINGER MANNHEIM GMBH

  公开号：EP0243808A2

  公开（公告）日：1987-11-04

  Isochinolindion-Derivate der allgemeinen Formel I in welcher R₁ ein Wasserstoffatom, eine Alkyl-, Alkenyl- oder eine Cyclo­alkylgruppe bedeutet, die gegebenenfalls durch ein Heteroatom oder durch ein mit einer Alkylgruppe substituiertes Hetero­atom unterbrochen ist, R₂ ein Wasserstoffatom, eine Alkyl-, Alkenyl- oder zusammen mit R₁ eine Cycloalkylen-, Alkyliden- und Cycloalkylidengruppe, die ggf. durch ein Heteroatom oder durch ein mit einer Alkyl­gruppe substituiertes Heteroatom unterbrochen ist, darstellen kann und R₃ eine Gruppe R₄R₅NCX- bedeutet, die in 5,6,7 oder 8-Stellung des Isochinolin-1,3-dions stehen kann und in der R₄ und R₅ gleich oder verschieden sein koennen und ein Wasserstoffatom, eine Alkyl-, Trihalogenalkyl-, Cycloalkyl-, Cycloalkenyl-, Di­alkylaminoalkyl-, Alkoxycarbonylalkyl-, Alkylcarbonyl-, Aryl- ­oder Hetarylgruppe und X Sauerstoff, Schwefel oder die Gruppe N-R₆, in der R₆ ein Wasserstoffatom, eine Alkyl- oder Cyan­gruppe ist, darstellen, sowie deren physiologisch verträg­liche Salze, Verfahren zu deren Herstellung und Arznei­mittel, die diese Verbindung enthalten, zur Behandlung und/oder Prophylaxe von Herz- und Kreislauferkrankungen.

  通式 I 的异喹啉二酮衍生物 其中 R₁ 是氢原子、烷基、烯基或环烷基，环烷基可任选被杂原子或被烷基取代的杂原子打断、 R₂ 可以代表氢原子、烷基、烯基或与 R₁ 一起代表环亚烷基、亚烷基和环亚烷基，它们可选择被杂原子或被烷基取代的杂原子打断，以及 R₃ 代表一个基团 R₄R₅NCX-，它可以位于异喹啉-1,3-二酮的 5、6、7 或 8 位，其中 R₄ 和 R₅ 可以相同或不同，以及一个氢原子、烷基、三卤代烷基、环烷基、环烯基、二烷基氨基烷基、烷氧羰基烷基、烷基羰基、芳基或 hetaryl 基团和 X 氧、硫或基团 N-R₆（其中 R₆为氢原子、烷基或氰基），以及其生理上可耐受的盐类、制备工艺和含有该化合物的治疗和/或预防心血管疾病的药物。