3,5-dimethyl-4-((2-(piperidin-4-ylamino)pyrimidin-4-yl)oxy)benzonitrile | 1033954-48-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3,5-dimethyl-4-((2-(piperidin-4-ylamino)pyrimidin-4-yl)oxy)benzonitrile
• 英文别名: 3,5-Dimethyl-4-[2-(piperidin-4-ylamino)pyrimidin-4-yl]oxybenzonitrile
• CAS: 1033954-48-1
• 化学式: C₁₈H₂₁N₅O
• 分子量: 323.398
• InChiKey: KZGFVTLOAJHTDA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  82.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,5-dimethyl-4-((2-(piperidin-4-ylamino)pyrimidin-4-yl)oxy)benzonitrile 在 水 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.5h， 生成
  参考文献：
  名称：

  一种取代嘧啶类衍生物及其制备方法和应用

  摘要：

  本发明公开了一种如通式I‑VI所示的取代嘧啶类化合物及其制备方法，以及含有一个或多个含此类化合物的组合物在制备治疗和预防人免疫缺陷病毒(HIV)药物中的应用。

  公开号：

  CN111187222B
• 作为产物：
  描述：

  1-Boc-4-氨基哌啶 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 生成 3,5-dimethyl-4-((2-(piperidin-4-ylamino)pyrimidin-4-yl)oxy)benzonitrile
  参考文献：
  名称：

  Discovery of piperidin-4-yl-aminopyrimidine derivatives as potent non-nucleoside HIV-1 reverse transcriptase inhibitors

  摘要：

  A novel series of piperidin-4-yl-aminopyrimidine derivatives were designed fusing the pharmacophore templates of etravirine VRX-480773 hybrids our group previously described and piperidine-linked aminopyrimidines. Most compounds displayed significantly improved activity against wild-type HIV-1 with EC50 values in single-digit nanomolar concentrations compared to etravirine VRX-480773 hybrids. Selected compounds were also evaluated for activity against reverse transcriptase, and had lower IC50 values than that of nevirapine. The improved potency observed in this in vitro model of HIV RNA replication partly validates the mechanism by which this class of allosteric pyrimidine derivatives inhibits reverse transcriptase, and represents a remarkable step forward in the development of AIDS therapeutics. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.050

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。
• 一种含三氮唑环的单芳基嘧啶类HIV-1逆转录酶抑制剂及其制备方法与应用
  申请人：山东大学

  公开号：CN110066273A

  公开（公告）日：2019-07-30

  本发明涉及含三氮唑环的单芳基嘧啶类HIV‑1逆转录酶抑制剂及其制备方法和应用。所述化合物具有式I或II所示的结构。本发明还涉及含有式I或II结构化合物的药物组合物。本发明还提供上述化合物以及含有一个或多个此类化合物的组合物在制备抗艾滋病药物中的应用。
• 吲哚哌啶嘧啶类衍生物及其制备方法和用途
  申请人：武汉工程大学

  公开号：CN114507218A

  公开（公告）日：2022-05-17

  本发明属于医药技术领域，具体涉及吲哚哌啶嘧啶类衍生物及其制备方法和用途。本发明所提供的衍生物具有较好的HIV‑1细胞水平抑制活性，其具有哌啶嘧啶类底物和吲哚类底物酰胺缩合的基本结构。且各化合物均具有低的细胞毒性和高的选择性指数，可用于进一步开发制备抗艾滋病药物。
• Targeting dual tolerant regions of binding pocket: Discovery of novel morpholine-substituted diarylpyrimidines as potent HIV-1 NNRTIs with significantly improved water solubility
  作者：Zhao Wang、Dongwei Kang、Da Feng、Srinivasulu Cherukupalli、Xiangyi Jiang、Zhipeng Fu、Erik De Clercq、Christophe Pannecouque、Xinyong Liu、Peng Zhan

  DOI：10.1016/j.ejmech.2020.112811

  日期：2020.11

  To address the intractable issues of drug resistance and poor solubility, a novel series of morpholine-substituted diarylpyrimidines targeting the tolerant region I and tolerant region II of NNIBP were rationally designed by utilizing the available crystallography studies. The biological evaluation results showed that four most promising compounds (14e1, 14g1, 14g2 and 14j2) displayed excellent potency against WT HIV-1 strain with EC(50 )values ranging from 58 to 87 nM, being far more potent than NVP and comparable to ETV. Besides, some derivatives exhibited moderate activity in inhibiting the mutant HIV-1 strains. More encouragingly, 14d2 (RF = 0.4) possessed higher antiresistance profile than ETV (RF = 6.3) and K-5a2 (RF = 3.0) toward the double mutant strain F227L + V106A. The HIV-1 RT inhibition assay confirmed their binding target. The molecular docking studies were conducted and discussed in detail to rationalize the preliminary SARs. Further test indicated that morpholine could indeed promote the improvement of water solubility. Additionally, the in silico prediction of physicochemical properties and CYP enzymatic inhibitory ability were investigated to evaluate their drug-like features. (C) 2020 Elsevier Masson SAS. All rights reserved.
• Discovery of piperidin-4-yl-aminopyrimidines as HIV-1 reverse transcriptase inhibitors. N-Benzyl derivatives with broad potency against resistant mutant viruses
  作者：Denis J. Kertesz、Christine Brotherton-Pleiss、Minmin Yang、Zhanguo Wang、Xianfeng Lin、Zongxing Qiu、Donald R. Hirschfeld、Shelley Gleason、Taraneh Mirzadegan、Pete W. Dunten、Seth F. Harris、Armando G. Villaseñor、Julie Qi Hang、Gabrielle M. Heilek、Klaus Klumpp

  DOI：10.1016/j.bmcl.2010.05.040

  日期：2010.7

  An analysis of the binding motifs of known HIV-1 non-nucleoside reverse transcriptase inhibitors has led to discovery of novel piperidine-linked aminopyrimidine derivatives with broad activity against wildtype as well as drug-resistant mutant viruses. Notably, the series retains potency against the K103 N/Y181C and Y188L mutants, among others. Thus, the N-benzyl compound 5k has a particularly attractive pro. le. Synthesis and SAR are presented and discussed, as well as crystal structures relating to the binding motifs. (C) 2010 Elsevier Ltd. All rights reserved.