6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)pyrimidine-2,4(1H,3H)-dione | 246264-76-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)pyrimidine-2,4(1H,3H)-dione
• 英文别名: 6-chloro-1-(2-trimethylsilylethoxymethyl) pyrimidine-2,4-dione；6-chloro-1-((2-trimethylsilylethoxy)methyl)uracil；6-chloro-1-(2-trimethylsilylethoxymethyl)pyrimidine-2,4-dione
• CAS: 246264-76-6
• 化学式: C₁₀H₁₇ClN₂O₃Si
• 分子量: 276.795
• InChiKey: RHSOGRMFLZYSKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)pyrimidine-2,4(1H,3H)-dione 、 双(3-氨基苯基)二硫化物 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 以90%的产率得到1-((2-trimethylsilylethoxy)methyl)-6-(3-aminophenylthio)uracil
  参考文献：
  名称：

  Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors

  摘要：

  New analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were synthesized and evaluated for their in vitro activities against HIV-1 in MT-4 cell cultures. Chemical diversity was introduced in 4 of the six positions of the core and the influence of each substituent was studied. This library was built on the basis of a rational diversity analysis with the objective of maximizing diversity and thus, the activity range with a minimum number of synthesized compounds. Among them, 2{1,2,3,1} and 2 {1,2,3,4} exhibited the most potent anti-HIV-1 activities (EC50 = 0.015 mu g/mL; 0.046 mu M, SI > 1667) and (EC50 = 0.025 mu g/mL; 0.086 mu M, SI > 1000), respectively, which were about 71-fold and 38-fold more active than the reference compound HEPT (EC50 = 1.01 mu g/ml; 3.27 mu M, SI > 25). (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.04.038
• 作为产物：
  描述：

  6-氯尿嘧啶 、 2-(三甲基硅烷基)乙氧甲基氯 在 sodium hydride 、 lithium bromide 作用下， 以 N-甲基吡咯烷酮 、 mineral oil 为溶剂， 反应 12.17h， 以400 mg的产率得到6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  [EN] SUBSTRATE ADAPTOR INHIBITORS OF PRMT5 AND USES THEREOF
  [FR] INHIBITEURS D'ADAPTATEUR DE SUBSTRAT DE PRMT5 ET LEURS UTILISATIONS

  摘要：

  本文提供了调节PRTM5活性的化合物。这些化合物可以抑制PRMT5与PRMT5底物适配器的结合。这些化合物可以调节PRMT5甲基转移酶活性，调节PRMT5调控的基因的转录，调节染色质结构调节，调节细胞分化，以及/或通过破坏PRMT5与PRMT5底物适配器的结合来调节mRNA剪接。此外，还提供了包含这些化合物的制药组合物，调节PRTM5活性的方法，以及通过给予本文所述的化合物或组合物治疗疾病（例如癌症）的方法。

  公开号：

  WO2022032144A1

文献信息

• [EN] PYRIMIDINEDIONE COMPOUNDS AGAINST CARDIAC CONDITIONS<br/>[FR] COMPOSÉS DE PYRIMIDINE-DIONE CONTRE LES AFFECTIONS CARDIAQUES
  申请人：MYOKARDIA INC

  公开号：WO2014205223A1

  公开（公告）日：2014-12-24

  Provided are novel pyrimidine dione compounds and pharmaceutically acceptable salts thereof, that are useful for the treatment of hypertrophic cardiomyopathy (HCM) and conditions associated with left ventricular hypertrophy or diastolic dysfunction. The synthesis and characterization of the compounds and pharmaceutically acceptable salts thereof, are described, as well as methods for treating HCM and other forms of heart disease.

  提供了新型嘧啶二酮化合物及其药用盐，可用于治疗肥厚型心肌病（HCM）和与左心室肥厚或舒张功能障碍相关的病症。描述了这些化合物及其药用盐的合成和表征，以及治疗HCM和其他形式心脏疾病的方法。
• [EN] SUBSTRATE ADAPTOR INHIBITORS OF PRMT5 AND USES THEREOF<br/>[FR] INHIBITEURS D'ADAPTATEUR DE SUBSTRAT DE PRMT5 ET LEURS UTILISATIONS
  申请人：BROAD INST INC

  公开号：WO2022032144A1

  公开（公告）日：2022-02-10

  Provided herein are compounds that modulate PRTM5 activity. The compounds may inhibit the binding PRMT5 with a PRMT5 substrate adaptor. The compounds can modulate PRMT5 methyltransferase activity, modulate transcription of a gene regulated by PRMT5, modulate chromatin structure regulation, modulate cellular differentiation, and/or modulate mRNA splicing, e.g., by disrupting binding of PRMT5 with a PRMT5 substrate adaptor. Also provided are pharmaceutical compositions comprising the compounds, methods of modulating PRTM5 activity, and methods of treating disease (e.g., cancer) in a subject by administering a compound or composition described herein.

  本文提供了调节PRTM5活性的化合物。这些化合物可以抑制PRMT5与PRMT5底物适配器的结合。这些化合物可以调节PRMT5甲基转移酶活性，调节PRMT5调控的基因的转录，调节染色质结构调节，调节细胞分化，以及/或通过破坏PRMT5与PRMT5底物适配器的结合来调节mRNA剪接。此外，还提供了包含这些化合物的制药组合物，调节PRTM5活性的方法，以及通过给予本文所述的化合物或组合物治疗疾病（例如癌症）的方法。
• GYRASE INHIBITORS
  申请人：Creighton Christopher J.

  公开号：US20130079323A1

  公开（公告）日：2013-03-28

  Novel gyrase inhibitors and related compositions and methods are useful for impeding bacterial growth. Compounds of Formula (I), are disclosed: Formula (I), wherein Y is N or CH; Z is N or CR 5 ; R 5 is H, a substituted or unsubstituted hydrocarbyl residue (1-3C) containing 0-2 heteroatoms selected from O, S and N, or is an inorganic residue; L is O, S, NR 7 , or CR 8 R 9 ; R 7 is H or C 1-3 alkyl; R 8 and R 9 are each independently H or C 1-3 alkyl; R 2 is H, a hydrocarbyl residue (1-40C) containing 0-10 heteroatoms selected from O, S and N optionally substituted with an inorganic residue; R 4 is H, an inorganic residue, or a hydrocarbyl residue (1-30C) containing 0-12 heteroatoms selected from O, S and N and containing 0-10 inorganic residues, wherein R 5 and R 4 together may join to form a fused ring; and R 6 is selected from the group consisting of H, C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, halo C 1-5 alkyl, halo C 2-5 alkenyl, halo C 2-5 alkynyl, C 1-5 hydroxyalkyl, C 1-5 alkyl chloride, C 2-5 alkenyl chloride, and C 2-5 alkynyl chloride; or a pharmaceutically-acceptable salt, ester, or prodrug thereof.

  新型螺旋酶抑制剂及相关组合物和方法，适用于阻碍细菌生长。其中公开了式（I）的化合物：式（I），其中Y为N或CH；Z为N或CR5；R5为H，含有0-2个来自O、S和N的杂原子的取代或未取代的碳氢基残基（1-3C），或为无机残基；L为O、S、NR7或CR8R9；R7为H或C1-3烷基；R8和R9各自独立地为H或C1-3烷基；R2为H，含有0-10个来自O、S和N的杂原子的碳氢基残基（1-40C），可选地取代为无机残基；R4为H、无机残基或含有0-12个来自O、S和N的杂原子和含有0-10个无机残基的碳氢基残基（1-30C），其中R5和R4可以共同形成融合环；R6选自H、C1-5烷基、C2-5烯基、C2-5炔基、卤代C1-5烷基、卤代C2-5烯基、卤代C2-5炔基、C1-5羟基烷基、C1-5氯代烷基、C2-5氯代烯基和C2-5氯代炔基的群；或其药学上可接受的盐、酯或前药。
• PYRIMIDINEDIONE COMPOUNDS
  申请人：MyoKardia, Inc.

  公开号：US20160030428A1

  公开（公告）日：2016-02-04

  Provided are novel pyrimidine dione compounds and pharmaceutically acceptable salts thereof, that are useful for the treatment of hypertrophic cardiomyopathy (HCM) and conditions associated with left ventricular hypertrophy or diastolic dysfunction. The synthesis and characterization of the compounds and pharmaceutically acceptable salts thereof, are described, as well as methods for treating HCM and other forms of heart disease.

  提供了新型嘧啶二酮化合物及其药学上可接受的盐，可用于治疗肥厚型心肌病（HCM）以及与左心室肥厚或舒张功能障碍有关的疾病。描述了该化合物及其药学上可接受的盐的合成和表征，以及治疗HCM和其他形式的心脏疾病的方法。
• Pyrimidinedione compounds
  申请人：MyoKardia, Inc.

  公开号：US09181200B2

  公开（公告）日：2015-11-10

  Provided are novel pyrimidine dione compounds and pharmaceutically acceptable salts thereof, that are useful for the treatment of hypertrophic cardiomyopathy (HCM) and conditions associated with left ventricular hypertrophy or diastolic dysfunction. The synthesis and characterization of the compounds and pharmaceutically acceptable salts thereof, are described, as well as methods for treating HCM and other forms of heart disease.

  提供了新型嘧啶二酮化合物及其药学上可接受的盐，可用于治疗肥厚型心肌病（HCM）和与左心室肥厚或舒张功能障碍相关的疾病。描述了该化合物及其药学上可接受的盐的合成和表征，以及治疗HCM和其他心脏疾病的方法。