rac-2-(3-Methyl-2-oxo-3-piperidinyl)-1H-isoindol-1,3(2H)-dion | 102818-62-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: rac-2-(3-Methyl-2-oxo-3-piperidinyl)-1H-isoindol-1,3(2H)-dion
• 英文别名: 2-(3-methyl-2-oxopiperidin-3-yl)isoindole-1,3-dione
• CAS: 102818-62-2
• 化学式: C₁₄H₁₄N₂O₃
• 分子量: 258.277
• InChiKey: YLIQJGQTTPUWNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  66.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  rac-2-(3-Methyl-2-oxo-3-piperidinyl)-1H-isoindol-1,3(2H)-dion 在 间氯过氧苯甲酸 作用下， 以 四氯化碳 、 乙醇 为溶剂， 反应 25.0h， 生成 1,3-Dimethylthalidomid
  参考文献：
  名称：

  3-烷基沙利度胺类似物的外消旋体和对映体的合成及其绝对构型的测定

  摘要：

  它是关于 3-烷基-沙利度胺类似物 7a - 7c 和外消旋体的外消旋体和对映体的合成。1,3-二甲基沙利度胺 (8) 已有报道。推导出光学活性合成产物的绝对构型。化合物7a-7c、8和合成中间体6a-6c将在动物实验中测试其镇静催眠作用。

  DOI：

  10.1002/ardp.19893220809
• 作为产物：
  描述：

  4-Cyano-2-methyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-butyric acid methyl ester 在 盐酸 、 platinum(IV) oxide 、 氢气 作用下， 生成 rac-2-(3-Methyl-2-oxo-3-piperidinyl)-1H-isoindol-1,3(2H)-dion
  参考文献：
  名称：

  (S)-Form of .ALPHA.-Methyl-N(.ALPHA.)-phthalimidoglutarimide, but Not Its (R)-Form, Enhanced Phorbol Ester-Induced Tumor Necrosis Factor-.ALPHA. Production by Human Leukemia Cell HL-60: Implication of Optical Resolution of Thalidomidal Effects.

  摘要：

  经测定，N(α)-邻苯二甲酰亚氨基戊二酰亚胺（沙利度胺）在 pH 值为 7.4/37°C 时的半衰期为 566 分钟。沙利度胺的这种快速外消旋化导致该化合物的(S)-型和(R)-型在增强人白血病 HL-60 细胞产生由光滑脂诱导的肿瘤坏死因子（TNF）-α 的活性方面没有明显差异。制备出了结构相关的沙利度胺类似物(S)-和(R)-α-甲基-N(α)-邻苯二甲酰亚胺戊二酰亚胺（甲基邻苯二甲酰亚胺）的光学纯形式，它们在生理条件下不会发生外消旋。只有(S)-形式的甲酞胺而不是其(R)-形式的甲酞胺能引起TNF-α生成增强效应，这表明甲酞胺的(S)-异构体是具有甲酞胺生物反应调节作用的活性形式。

  DOI：

  10.1248/cpb.42.1157

文献信息

• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR
  申请人：Arvinas, Inc.

  公开号：US20180099940A1

  公开（公告）日：2018-04-12

  The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.

  本公开涉及双功能化合物，其用于降解和（抑制）雄激素受体。具体而言，本公开涉及包含一端结合到E3泛素连接酶的谷氨酰腺苷环配体，另一端结合到雄激素受体的部分的化合物，使得雄激素受体与泛素连接酶靠近，以实现雄激素受体的降解（和抑制）。本公开展示了与根据本公开涉及的化合物相关的广泛的药理活性范围，与雄激素受体的降解/抑制一致。
• Substituted heteroaryl pyridopyrimidone derivatives
  申请人：Sanofi-Aventis

  公开号：EP1939187A1

  公开（公告）日：2008-07-02

  A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof : wherein: Y represents two hydrogen atoms, a sulfur atom, an oxygen atom or a C1-2 alkyl group and a hydrogen atom; Z represents a bond, an oxygen atom, a nitrogen atom, a sulphur atom, a methylene group optionally substituted by one or two groups chosen from a C1-6 alkyl group, a hydroxyl group, a C1-6 alkoxy group, a C1-2 perhalogenated alkyl group or an amino group; R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring; R2 represents a 4-15 membered heterocyclic group , R3 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom; R4 and R5 represent, each independently, a hydrogen atom, a C1-6 alkyl group, optionally substituted by 1 to 4 substituents selected from a halogen atom, a phenyl group, a hydroxyl group or a C1-6 alkoxy group; R6 represents a hydrogen atom, a C1-6 alkyl group ; a cycloalkyl group, or a halogen atom; R7 represents a hydrogen atom or a C1-6 alkyl group; n represents 0 to 3; m represents 0 to 1; o represents 0 to 2; in the form of a free base or of an addition salt with an acid. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β, such as Alzheimer disease.

  公式（I）表示的嘧啶酮衍生物或其盐，溶剂化合物或水合物：其中：Y代表两个氢原子、硫原子、氧原子或C1-2烷基基团和一个氢原子；Z代表键、氧原子、氮原子、硫原子、一个亚甲基基团，可选地由C1-6烷基基团、羟基、C1-6烷氧基、C1-2全卤代烷基或氨基中选择的一种或两种基团取代的亚甲基基团；R1代表2、3或4-吡啶环或2、4或5-嘧啶环；R2代表4-15成员的杂环基团，R3代表氢原子、C1-6烷基基团或卤原子；R4和R5分别代表氢原子、C1-6烷基基团，可选地取代1至4个取代基，所选取代基来自卤原子、苯基、羟基或C1-6烷氧基；R6代表氢原子、C1-6烷基基团；环烷基基团或卤原子；R7代表氢原子或C1-6烷基基团；n表示0到3；m表示0到1；o表示0到2；以自由碱或与酸的加成盐的形式存在。该发明还涉及一种药物，包括所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β异常活性引起的神经退行性疾病，如阿尔茨海默病。
• SUBSTITUTED BICYCLIC PYRIMIDONE DERIVATIVES
  申请人：CHEREZE Nathalie

  公开号：US20090036427A1

  公开（公告）日：2009-02-05

  A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof: Wherein Y, Z, R1, R2, R3, R4, R5, R6, R7, n, m, and o are as described herein. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β, such as Alzheimer disease.

  一种由式（I）表示的吡啶酮衍生物或其盐、溶剂或水合物：其中Y、Z、R1、R2、R3、R4、R5、R6、R7、n、m和o如所述。本发明还涉及一种药物，其包含所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β异常活性引起的神经退行性疾病，如阿尔茨海默病。
• SUBSTITUTED HETEROARYL PYRIDOPYRIMIDONE DERIVATIVES
  申请人：FAYOL Aude

  公开号：US20090306088A1

  公开（公告）日：2009-12-10

  A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof are disclosed and claimed. Wherein m, n, o, Y, Z, R1, R2, R3, R4, R5 R6 and R7 are as described herein. Also disclosed are the salts of compounds of formula (I). The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β, such as Alzheimer disease.

  本发明揭示和声明了由式(I)表示的吡啶酮衍生物，或其盐、溶剂或水合物。其中m、n、o、Y、Z、R1、R2、R3、R4、R5、R6和R7如本文所述。本发明还揭示了式(I)化合物的盐。本发明涉及一种药物，其包括所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β异常活性引起的神经退行性疾病，如阿尔茨海默病。
• Substituted bicyclic pyrimidone derivatives
  申请人：Sanofi-Aventis

  公开号：US08148364B2

  公开（公告）日：2012-04-03

  A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof: Wherein Y, Z, R1, R2, R3, R4, R5, R6, R7, n, m, and o are as described herein. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β, such as Alzheimer disease.

  一种由式（I）表示的吡啶酮衍生物或其盐、溶剂或水合物： 其中，Y、Z、R1、R2、R3、R4、R5、R6、R7、n、m和o如本文所述。本发明还涉及一种药物，包括所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β异常活性引起的神经退行性疾病，如阿尔茨海默病。