4-[(2,5-dichloro-4-pyrimidinyl)oxy]-3,5-dimethylbenzonitrile | 1033955-60-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[(2,5-dichloro-4-pyrimidinyl)oxy]-3,5-dimethylbenzonitrile
• 英文别名: 4-(2,5-Dichloropyrimidin-4-yl)oxy-3,5-dimethylbenzonitrile；4-(2,5-dichloropyrimidin-4-yl)oxy-3,5-dimethylbenzonitrile
• CAS: 1033955-60-0
• 化学式: C₁₃H₉Cl₂N₃O
• mdl: MFCD22715669
• 分子量: 294.14
• InChiKey: ASKBGQDCWCQCST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.153
• 拓扑面积：
  58.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[(2,5-dichloro-4-pyrimidinyl)oxy]-3,5-dimethylbenzonitrile 、 1-(2-氨基-乙基)-1H-嘧啶-2,4-二酮盐酸盐 在 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 以36.7%的产率得到4-((5-chloro-2-((2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethyl)amino)pyrimidin-4-yl)oxy)-3,5-dimethylbenzonitrile
  参考文献：
  名称：

  Discovery of uracil-bearing DAPYs derivatives as novel HIV-1 NNRTIs via crystallographic overlay-based molecular hybridization

  摘要：

  A novel series of uracil-bearing DAPYs derivatives were designed and synthesized via structure-based molecular hybridization to discover compounds with improved anti-resistance profiles. Anti-HIV activity of the designed compounds was tested in MT-4 cell cultures. The most promising compound 16d showed excellent activity with EC50 value of 5.6 nM against wide-type HIV-1 and low cytotoxicity (SI > 50000). Activity against the clinic prevalent mutant strains was also tested, suggesting that 16d was sensitive to E138K (EC50 = 34.2 nM). Primary drug-like properties, such as water solubility and logP, were evaluated by experiment or calculation, which indicated that introducing an uracil can improve solubility. The molecular modeling accompanied with the preliminary SAR correlations paved the way for the next round of rational design of potent anti-HIV agents. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.047
• 作为产物：
  描述：

  3,5-二甲基-4-羟基苯甲腈 、 2,4,5-三氯嘧啶 在 potassium carbonate 作用下， 以75%的产率得到4-[(2,5-dichloro-4-pyrimidinyl)oxy]-3,5-dimethylbenzonitrile
  参考文献：
  名称：

  Discovery of uracil-bearing DAPYs derivatives as novel HIV-1 NNRTIs via crystallographic overlay-based molecular hybridization

  摘要：

  A novel series of uracil-bearing DAPYs derivatives were designed and synthesized via structure-based molecular hybridization to discover compounds with improved anti-resistance profiles. Anti-HIV activity of the designed compounds was tested in MT-4 cell cultures. The most promising compound 16d showed excellent activity with EC50 value of 5.6 nM against wide-type HIV-1 and low cytotoxicity (SI > 50000). Activity against the clinic prevalent mutant strains was also tested, suggesting that 16d was sensitive to E138K (EC50 = 34.2 nM). Primary drug-like properties, such as water solubility and logP, were evaluated by experiment or calculation, which indicated that introducing an uracil can improve solubility. The molecular modeling accompanied with the preliminary SAR correlations paved the way for the next round of rational design of potent anti-HIV agents. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.047

文献信息

• Non-nucleoside reverse transcriptase inhibitors
  申请人：Kestesz Denis John

  公开号：US20080146595A1

  公开（公告）日：2008-06-19

  The present invention provides for compounds useful for treating an HIV infection, or preventing an HIV infection, or treating AIDS or ARC. The compounds of the invention are of formula I wherein R 1 , R 2 , R 3 , R 4 , R 5a , R 5b , R 6a , R 6b and X are as herein defined. Also disclosed in the present invention are methods of treating an HIV infection with compounds defined herein and pharmaceutical compositions containing said compounds.

  本发明提供了用于治疗HIV感染、预防HIV感染、治疗AIDS或ARC的化合物。本发明的化合物具有如下式I所示的结构，其中R1、R2、R3、R4、R5a、R5b、R6a、R6b和X的定义如本文所述。本发明还公开了使用上述定义的化合物治疗HIV感染的方法，以及含有这些化合物的药物组合物。
• Exploration of piperidine-4-yl-aminopyrimidines as HIV-1 reverse transcriptase inhibitors. N-Phenyl derivatives with broad potency against resistant mutant viruses
  作者：Guozhi Tang、Denis J. Kertesz、Minmin Yang、Xianfeng Lin、Zhanguo Wang、Wentao Li、Zongxing Qiu、Junli Chen、Jianghua Mei、Li Chen、Taraneh Mirzadegan、Seth F. Harris、Armando G. Villaseñor、Jennifer Fretland、William L. Fitch、Julie Qi Hang、Gabrielle Heilek、Klaus Klumpp

  DOI：10.1016/j.bmcl.2010.08.068

  日期：2010.10

  Further investigation of the recently reported piperidine-4-yl-aminopyrimidine class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) has been carried out. Thus, preparation of a series of N-phenyl piperidine analogs resulted in the identification of 3-carboxamides as a particularly active series. Analogs such as 28 and 40 are very potent versus wild-type HIV-1 and a broad range of NNRTI-resistant mutant viruses. Synthesis, structure-activity relationship (SAR), clearance data, and crystallographic evidence for the binding motif are discussed. (c) 2010 Elsevier Ltd. All rights reserved.
• 2-(PIPERIDIN-4-YL)-4-PHENOXY-OR PHENYLAMINO-PYRIMIDINE DERIVATIVES AS NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2089384B1

  公开（公告）日：2015-08-05
• [EN] NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS<br/>[FR] INHIBITEURS NON NUCLÉOSIDIQUES DE LA TRANSCRIPTASE INVERSE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2008071587A2

  公开（公告）日：2008-06-19

  [EN] The present invention provides for compounds useful for treating an HIV infection, or preventing an HIV infection, or treating AIDS or ARC. The compounds of the invention are of formula (I) wherein R¹, R², R³, R⁴, R^5a, R^5b, R^6a, R^6b and X are as herein defined. Also disclosed in the present invention are methods of treating an HIV infection with compounds defined herein and pharmaceutical compositions containing said compounds.
  [FR] La présente invention concerne des composés utiles pour traiter une infection par le VIH, ou prévenir une infection par le VIH, ou traiter le SIDA ou le SAS. Les composés de l'invention sont de formule I dans laquelle R¹, R², R³, R⁴, R^5a, R^5b, R^6a, R^6b et X sont tels que définis ici. La présente invention concerne également des procédés de traitement d'une infection par le VIH avec les composés définis ici et des compositions pharmaceutiques contenant lesdits composés.