1-(6-bromo-5-fluoro-1-methylindazol-3-yl)hexahydropyrimidine-2,4-dione | 2760850-50-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 1-(6-bromo-5-fluoro-1-methylindazol-3-yl)hexahydropyrimidine-2,4-dione
• 英文别名: 1-(6-Bromo-5-fluoro-1-methyl-1H-indazol-3-yl)dihydropyrimidine-2,4(1H,3H)-dione；1-(6-bromo-5-fluoro-1-methylindazol-3-yl)-1,3-diazinane-2,4-dione
• CAS: 2760850-50-6
• 化学式: C₁₂H₁₀BrFN₄O₂
• 分子量: 341.139
• InChiKey: KFKVWUYFOMKILO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(6-bromo-5-fluoro-1-methylindazol-3-yl)hexahydropyrimidine-2,4-dione 在 盐酸 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 10 wt% Pd(OH)2 on carbon 、 caesium carbonate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、101.33 kPa 条件下， 反应 47.0h， 生成 tert-butyl 2-[4-[3-(2,4-dioxohexahydropyrimidin-1-yl)-5-fluoro-1-methylindazol-6-yl]-1-piperidyl]acetate
  参考文献：
  名称：

  [EN] THERAPEUTICS FOR THE DEGRADATION OF MUTANT BRAF
  [FR] AGENTS THÉRAPEUTIQUES POUR LA DÉGRADATION DE BRAF MUTANTE

  摘要：

  公开号：

  WO2022261250A8
• 作为产物：
  描述：

  ethyl 3-[(6-bromo-5-fluoro-1-methylindazol-3-yl)amino]propanoate 在 indium(III) chloride 、 乙醛肟 、 sodium acetate 、 苄基三甲基氢氧化铵 作用下， 以 甲醇 、 乙醇 、 甲苯 、 乙腈 为溶剂， 反应 18.0h， 生成 1-(6-bromo-5-fluoro-1-methylindazol-3-yl)hexahydropyrimidine-2,4-dione
  参考文献：
  名称：

  [EN] THERAPEUTICS FOR THE DEGRADATION OF MUTANT BRAF
  [FR] AGENTS THÉRAPEUTIQUES POUR LA DÉGRADATION DE BRAF MUTANTE

  摘要：

  公开号：

  WO2022261250A8

文献信息

• [EN] COMPOUNDS FOR TARGETED DEGRADATION OF RET<br/>[FR] COMPOSÉS POUR LA DÉGRADATION CIBLÉE DE RET
  申请人：C4 THERAPEUTICS INC

  公开号：WO2022032026A1

  公开（公告）日：2022-02-10

  Novel compounds which act as protein degradation inducing moieties for proto-oncogene tyrosine-protein kinase receptor (RET), which may be either wild type RET or a mutant form of RET.

  新型化合物，可作为蛋白质降解诱导因子，作用于原癌基因酪氨酸蛋白激酶受体（RET），该受体可能是野生型RET或突变型RET。
• [EN] COMPOUNDS FOR TARGETING DEGRADATION OF BRUTON'S TYROSINE KINASE<br/>[FR] COMPOSÉS DESTINÉS À CIBLER LA DÉGRADATION DE LA TYROSINE KINASE DE BRUTON
  申请人：BIOGEN MA INC

  公开号：WO2022235945A1

  公开（公告）日：2022-11-10

  This disclosure relates to compounds of Formula (A): BTK— L— DSM (A) or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches BTK to DSM, and BTK is a Btk binding moiety represented by Formula (I) or Formula (II) that is covalently attached to linker L: in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of Btk proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of Btk proteins. The present disclosure also provides methods of treating disorders responsive to modulation of Btk activity and/or degradation of Btk with at least one compound described herein.

  本公开涉及式(A)化合物：BTK-L-DSM(A)或其药学上可接受的盐，其中DSM是降解信号基团，与连接基L共价结合，L是将BTK与DSM共价连接的连接基，而BTK是由式(I)或式(II)表示的结合BTk的基团，其与连接基L共价连接。其中所有变量均如所述申请中定义。如本文所述的化合物或其药学上可接受的盐能够通过泛素-蛋白酶体途径（UPP）激活选择性泛素化BTk蛋白并导致BTk蛋白的降解。本公开还提供了使用至少一种本文所述化合物治疗对BTk活性调节和/或BTk降解具有反应的疾病的方法。
• [EN] COMPOUNDS FOR TARGETING DEGRADATION OF IRAK4 PROTEINS<br/>[FR] COMPOSÉS POUR LE CIBLAGE DE LA DÉGRADATION DE PROTÉINES IRAK4
  申请人：[en]BIOGEN MA INC.

  公开号：WO2023283610A1

  公开（公告）日：2023-01-12

  This disclosure relates to compounds of Formula (A): IRAK—L—DSM (A), or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches IRAK to DSM; and IRAK is an IRAK4 binding moiety represented by Formula (I) that is covalently attached to linker L; in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of IRAK4 proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of IRAK4 proteins. The present disclosure also provides methods of treating disorders responsive to modulation of IRAK4 activity and/or degradation of IRAK4 with at least one compound described herein.
• [EN] CORONAVIRUS NON-STRUCTURAL PROTEIN 3 DEGRADING COMPOUNDS<br/>[FR] COMPOSÉS DE DÉGRADATION DE LA PROTÉINE 3 NON STRUCTURALE DE CORONAVIRUS
  申请人：[en]C4 THRAPEUTICS, INC.

  公开号：WO2023059792A1

  公开（公告）日：2023-04-13

  This invention provides advantageous compounds for the treatment of hosts, including humans, infected with a coronavirus, including but not limited to SARS-CoV-2.