RA190

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: RA190
• 英文别名: (3E,5E)-1-[(2S)-2-amino-3-phenylpropanoyl]-3,5-bis[(3,4-dichlorophenyl)methylidene]piperidin-4-one
• 化学式: C₂₈H₂₂Cl₄N₂O₂
• 分子量: 560.307
• InChiKey: IYJSFPQYTFFTKN-KJRZKRENSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  63.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  RA190 在 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 6-((1-((1-(3,5-bis((E)-3,4-dichlorobenzylidene)-4-oxopiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl)glycyl)azetidin-3-yl)amino)-N-((S)-3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamide
  参考文献：
  名称：

  [EN] ARGININE METHYLTRANSFERASE 5 (PRMT5) DEGRADERS AND USES THEREOF
  [FR] AGENTS DE DÉGRADATION DE L'ARGININE MÉTHYLTRANSFÉRASE 5 (PRMT5) ET LEURS UTILISATIONS

  摘要：

  本文披露了一种针对PRMT5进行降解的双功能化合物，以及用于治疗由异常的精氨酸甲基转移酶5（PRMT5）活性介导的疾病或病况的组合物和方法。

  公开号：

  WO2021207052A1

文献信息

• [EN] SMALL MOLECULE RPN13 INHIBITORS WITH ANTITUMOR PROPERTIES<br/>[FR] INHIBITEURS DE RPN13 À PETITES MOLÉCULES AYANT DES PROPRIÉTÉS ANTITUMORALES
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2021113743A1

  公开（公告）日：2021-06-10

  Compounds of formula (I), (II), and (III) having the structure shown below are presented: wherein R-R6 are defined herein. These molecules work as proteasome inhibitors and bind to the RPN13 subunit of the 19S regulatory particle, and can be used in methods of treating a condition or a disease, such as cancer, in a mammal.

  化合物的结构如下所示，其化学式为(I)，(II)，和(III)，其中R-R6在此处定义。这些分子作为蛋白酶体抑制剂，并结合到19S调节粒子的RPN13亚基，可用于治疗哺乳动物的疾病或病症，如癌症。
• [EN] ANTI-CANCER SPIROCYCLIC-GUANIDINE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS GUANIDINE SPIROCYCLIQUES ANTICANCÉREUX ET LEURS UTILISATIONS
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2021236654A1

  公开（公告）日：2021-11-25

  The invention of the instant application discloses spirocyclic guanidine compounds of general formula (I), shown below, and their use in methods of treating cancer

  本发明的即时申请揭示了通式（I）所示的螺环鸟氨酸化合物及其在治疗癌症的方法中的使用。
• WO2019/165229
  申请人：——

  公开号：——

  公开（公告）日：——
• SMALL MOLECULES FOR INDUCING SELECTIVE PROTEIN DEGRADATION AND USES THEREOF
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20200407371A1

  公开（公告）日：2020-12-31

  Provided herein are bifunctional compounds that bind a target protein (e.g., a selected protein) and/or induce ubiquitination for degradation of the target protein. In particular, provided are compounds that bind a bromodomain or bromodomain-containing protein (e.g., BET proteins) or histone methyltransferases (HMTs, e.g., enhancer of zeste homolog 1 (EZH1), or FKBP12) and can promote its degradation by recruiting it to the ubiquitin receptor RPN13 (e.g., RA190), for proteasomal degradation. Also provided are pharmaceutical compositions comprising the bifunctional compounds, methods of treating and/or preventing diseases (e.g., proliferative diseases, cancers, benign neoplasms, pathological angiogenesis, inflammatory diseases, and autoimmune diseases) and musculoskeletal diseases, and methods of inducing the degradation of a target (e.g., a target protein) by recruiting it to the ubiquitin receptor RPN13 of the proteasome in a subject by administering a compound or composition described herein.
• SMALL MOLECULES THAT BLOCK PROTEASOME-ASSOCIATED UBIQUITIN RECEPTOR RPN13 FUNCTION AND USES THEREOF
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20210130324A1

  公开（公告）日：2021-05-06

  Provided herein are bifunctional compounds with a moiety (e.g., lenalidomide, thalidomide) that is a binder of an E3 ubiquitin ligase (e.g., Cereblon) and another moiety (e.g., RA190) that is a binder of the ubiquitin receptor RPN13 to induce degradation of RPN13 and thereby inhibit proteasome function. Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases, cancers, benign neoplasms, pathological angiogenesis, inflammatory diseases, and autoimmune diseases). Provided also are methods of inducing the degradation of ubiquitin receptor RPN13 by administering a bifunctional compound or composition described herein, wherein one component of the bifunctional compound is a binder of an E3 ubiquitin ligase (e.g., lenalidomide, thalidomide) and another component of the compound is a binder of ubiquitin receptor RPN13 (e.g., RA190) in a subject.