N-[4-Chloro-3-(phenylsulfanyl)phenyl]-4-methoxypyrimidin-2-amine | 915774-27-5

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: N-[4-Chloro-3-(phenylsulfanyl)phenyl]-4-methoxypyrimidin-2-amine
• 英文别名: N-(4-chloro-3-phenylsulfanylphenyl)-4-methoxypyrimidin-2-amine
• CAS: 915774-27-5
• 化学式: C₁₇H₁₄ClN₃OS
• 分子量: 343.837
• InChiKey: JDAXEXFHTCPZLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  72.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  苯硫酚铜(I) 在 吡啶 、 对甲苯磺酸 、 tin(ll) chloride 作用下， 以 喹啉 为溶剂， 生成 N-[4-Chloro-3-(phenylsulfanyl)phenyl]-4-methoxypyrimidin-2-amine
  参考文献：
  名称：

  Optimization of pyrimidinyl- and triazinyl-amines as non-nucleoside inhibitors of HIV-1 reverse transcriptase

  摘要：

  Non-nucleoside inhibitors of HIV-1 reverse transcriptase are being pursued through synthesis and assaying for anti-viral activity. Following computational analyses, the focus has been on the motif Het-NH-Ph-U, where Het is an aromatic heterocycle and U is an unsaturated, hydrophobic group. Previous investigations with Het = 2-thiazoyl and 2-pyrimidinyl are extended here to triazinyl derivatives. The result is several NNRTIs in the 2-20 nM range with negligible cytotoxicity and auspicious predicted pharmacological properties. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.08.037

文献信息

• Compounds and Methods for the Treatment of Viruses and Cancer
  申请人：Jorgensen William L.

  公开号：US20100222352A1

  公开（公告）日：2010-09-02

  The present invention relates to compounds according to the formula I: Where R a is H or an optionally OH-substituted C 1 -C 3 alkyl; R 1 is OR 1 , an optionally substituted C 4-12 carbocyclic group which may be saturated or unsaturated (including aromatic) or an optionally substituted heterocyclic group; R 1 is an optionally substituted C 1 -C 14 hydrocarbyl group or an optionally substituted heterocyclic group; R 2 , R 3 and R 4 are each independently H, an optionally substituted C 1 -C 4 alkyl group (preferably CH 3 , CH 2 CH 3 or CF 3 ), halogen (preferably F, Cl, Br), OR, CN, NO 2 , a C 1 -C 6 thioether, a C 1 -C 6 thioester group, an optionally substituted CO 2 R group, an optionally substituted COR group or an optionally substituted OCOR group (preferably R 4 is H); R is H or an optionally substituted C 1 -C 6 alkyl group; RHET is an optionally substituted heterocyclic group; and pharmaceutically acceptable salts, solvates or polymorphs thereof.

  本发明涉及公式I的化合物：其中R为H或可选择的OH取代的C1-C3烷基; R1为OR1，可选择取代的C4-12碳环基，可饱和或不饱和（包括芳香族）或可选择取代的杂环基; R1为可选择取代的C1-C14烃基或可选择取代的杂环基; R2、R3和R4各自独立地为H、可选择取代的C1-C4烷基（优选为CH3、CH2CH3或CF3）、卤素（优选为F、Cl、Br）、OR、CN、NO2、C1-C6硫醚、C1-C6硫酯基、可选择取代的CO2R基团、可选择取代的COR基团或可选择取代的OCOR基团（优选R4为H）; R为H或可选择取代的C1-C6烷基; RHET为可选择取代的杂环基;以及其药学上可接受的盐、溶剂或多晶体。
• WO2007/38387
  申请人：——

  公开号：——

  公开（公告）日：——
• Efficient Discovery of Potent Anti-HIV Agents Targeting the Tyr181Cys Variant of HIV Reverse Transcriptase
  作者：William L. Jorgensen、Mariela Bollini、Vinay V. Thakur、Robert A. Domaoal、Krasimir A. Spasov、Karen S. Anderson

  DOI：10.1021/ja2058583

  日期：2011.10.5

  Non-nucleoside reverse transcriptase inhibitors (NNRTIs) that interfere with the replication of human immunodeficiency virus (HIV) are being pursued with guidance from molecular modeling including free-energy perturbation (FEP) calculations for protein inhibitor binding affinities. The previously reported pyrimidinylphenylamine 1 and its chloro analogue 2 are potent anti-HIV agents; they inhibit replication of wild-type HIV-1 in infected human T-cells with EC50 values of 2 and 10 nM, respectively. However, they show no activity against viral strains containing the Tyr181Cys (Y181C) mutation in HIV-RT. Modeling indicates that the problem is likely associated with extensive interaction between the dimethylallyloxy substituent and Tyr181. As an alternative, a phenoxy group is computed to be oriented in a manner diminishing the contact with Tyr181. However, this replacement leads to a roughly 1000-fold loss of activity for 3 (2.5 mu M). The present report details the efficient, computationally driven evolution of 3 to novel NNRTIs with sub-10 nM potency toward both wild-type HIV-1 and Y181C-containing variants. The critical contributors were FEP substituent scans for the phenoxy and pyrimidine rings and recognition of potential benefits of addition of a cyanovinyl group to the phenoxy ring.
• US9018209B2
  申请人：——

  公开号：US9018209B2

  公开（公告）日：2015-04-28
• Optimization of pyrimidinyl- and triazinyl-amines as non-nucleoside inhibitors of HIV-1 reverse transcriptase
  作者：Vinay V. Thakur、Joseph T. Kim、Andrew D. Hamilton、Christopher M. Bailey、Robert A. Domaoal、Ligong Wang、Karen S. Anderson、William L. Jorgensen

  DOI：10.1016/j.bmcl.2006.08.037

  日期：2006.11

  Non-nucleoside inhibitors of HIV-1 reverse transcriptase are being pursued through synthesis and assaying for anti-viral activity. Following computational analyses, the focus has been on the motif Het-NH-Ph-U, where Het is an aromatic heterocycle and U is an unsaturated, hydrophobic group. Previous investigations with Het = 2-thiazoyl and 2-pyrimidinyl are extended here to triazinyl derivatives. The result is several NNRTIs in the 2-20 nM range with negligible cytotoxicity and auspicious predicted pharmacological properties. (c) 2006 Elsevier Ltd. All rights reserved.