6-[(1-acetylpiperidin-4-yl)amino]-N-[3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]pyrimidine-4-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 6-[(1-acetylpiperidin-4-yl)amino]-N-[3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]pyrimidine-4-carboxamide
• 化学式: C₂₄H₃₂N₆O₃
• 分子量: 452.5
• InChiKey: JLCCNYVTIWRPIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  7

文献信息

• [EN] CRYSTALLINE SALTS OF (S)-6-((1-ACETYLPIPERIDIN-4-YL)AMINO)-N-(3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YL)-2-HYDROXYPROPYL)PYRIMIDINE-4-CARBOXAMIDE<br/>[FR] SELS CRISTALLINS DE (S)-6-((1-ACÉTYLPIPÉRIDIN-4-YL)AMINO)-N-(3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YL)-2-HYDROXYPROPYL)PYRIMIDINE-4-CARBOXAMIDE
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2015198229A1

  公开（公告）日：2015-12-30

  Disclosed are novel crystalline salts of (S)-6-((1-acetylpiperidin-4-yl)amino)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamide and pharmaceutical compositions containing the same. Also disclosed are processes for the preparation thereof and methods for use thereof.

  揭示了(S)-6-((1-乙酰基哌啶-4-基)氨基)-N-(3-(3,4-二氢异喹啉-2(1H)-基)-2-羟基丙基)嘧啶-4-甲酰胺的新型晶体盐，以及含有该盐的药物组合物。还揭示了其制备方法和使用方法。
• PRMT5 INHIBITORS AND USES THEREOF
  申请人：Epizyme, Inc.

  公开号：US20140329794A1

  公开（公告）日：2014-11-06

  Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

  本文描述了公式（I）的化合物，其药学上可接受的盐以及其制药组合物。本发明的化合物可用于抑制PRMT5活性。还描述了使用这些化合物治疗PRMT5介导的疾病的方法。
• TETRAHYDRO- AND DIHYDRO-ISOQUINOLINE PRMT5 INHIBITORS AND USES THEREOF
  申请人：EPIZYME, INC.

  公开号：US20150344434A1

  公开（公告）日：2015-12-03

  Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5 mediated disorders are also described.

  本文描述了公式（A）的化合物，其药学上可接受的盐以及它们的药物组合物。本发明的化合物对于抑制PRMT5活性是有用的。还描述了使用这些化合物治疗PRMT5介导的疾病的方法。
• SUBSTITUTED 4-AMINOISOINDOLINE-1,3-DIONE COMPOUNDS AND SECOND ACTIVE AGENTS FOR COMBINED USE
  申请人：Celgene Corporation

  公开号：US20210113576A1

  公开（公告）日：2021-04-22

  Provided herein are methods of using (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiomer, mixture of enantiomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing or managing hematological malignancies. The second active agent is one or more of an HDAC inhibitor, a BCL2 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PI3K inhibitor, a PKCβ inhibitor, a SYK inhibitor, a JAK2 inhibitor, an Aurora kinase inhibitor, an EZH2 inhibitor, a BET inhibitor, a hypomethylating agent, a DOT1L inhibitor, a HAT inhibitor, a WDR5 inhibitor, a DNMT1 inhibitor, an LSD-1 inhibitor, a G9A inhibitor, a PRMT5 inhibitor, a BRD inhibitor, a SUV420H1/H2 inhibitor, a CARM1 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an MEK inhibitor, a PHF19 inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a BIRC5 inhibitor, or a chemotherapy.

  本文提供了使用(S)-2-(2,6-二酮哌啶-3-基)-4-((2-氟-4-((3-吗啡基氮杂环丙烷-1-基)甲基)苯甲基)氨基)异吲哚啉-1,3-二酮或其对映体、对映体混合物、互变异构体、同位素拓扑异构体或其药学上可接受的盐，与第二种活性剂联合治疗、预防或管理血液恶性肿瘤的方法。第二种活性剂是HDAC抑制剂、BCL2抑制剂、BTK抑制剂、mTOR抑制剂、PI3K抑制剂、PKCβ抑制剂、SYK抑制剂、JAK2抑制剂、极化分裂素激酶抑制剂、EZH2抑制剂、BET抑制剂、去甲基化剂、DOT1L抑制剂、HAT抑制剂、WDR5抑制剂、DNMT1抑制剂、LSD-1抑制剂、G9A抑制剂、PRMT5抑制剂、BRD抑制剂、SUV420H1/H2抑制剂、CARM1抑制剂、PLK1抑制剂、NEK2抑制剂、MEK抑制剂、PHF19抑制剂、PIM抑制剂、IGF-1R抑制剂、XPO1抑制剂、BIRC5抑制剂或化疗药物之一。
• METHODS FOR TREATING A HEMATOLOGICAL CANCER AND THE USE OF COMPANION BIOMARKERS FOR 2-(2,6-DIOXOPIPERIDIN-3-YL)-4-((2-FLUORO-4-((3-MORPHOLINOAZETIDIN-1-YL)METHYL)BENZYL)AMINO)ISOINDOLINE-1,3-DIONE
  申请人：CELGENE CORPORATION

  公开号：US20210116454A1

  公开（公告）日：2021-04-22

  A method of identifying a subject having a hematological cancer who is likely to be responsive to a treatment compound, comprising administering the treatment compound to the subject having the hematological cancer; obtaining a sample from the subject; determining the level of a biomarker in the sample from the subject; and diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject changes as compared to a reference level of the biomarker; wherein the treatment compound is Compound 1, Compound 2, or Compound 3.

  一种识别可能对治疗化合物有反应的血液肿瘤患者的方法，包括给患有血液肿瘤的受试者注射治疗化合物，从受试者获取样本，测定样本中生物标志物的水平，并在与生物标志物的参考水平相比，如果受试者样本中生物标志物的水平发生变化，则诊断受试者可能对治疗化合物有反应；其中，治疗化合物是化合物1、化合物2或化合物3。