6-(diethoxymethyl)-2-<(2-naphthalenylmethyl)thio>-4-pyrimidinol | 185219-79-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-(diethoxymethyl)-2-<(2-naphthalenylmethyl)thio>-4-pyrimidinol
• 英文别名: 4-(Diethoxymethyl)-6-hydroxy-2-(2-naphthylmethyl)-thio-pyrimidine；4-(diethoxymethyl)-2-(naphthalen-2-ylmethylsulfanyl)-1H-pyrimidin-6-one
• CAS: 185219-79-8
• 化学式: C₂₀H₂₂N₂O₃S
• 分子量: 370.472
• InChiKey: YSTWVVUTSGZEFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  85.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(diethoxymethyl)-2-<(2-naphthalenylmethyl)thio>-4-pyrimidinol 在 溶剂黄146 作用下， 反应 2.0h， 生成 6-Hydroxy-2-(naphthalen-2-ylmethylsulfanyl)-pyrimidine-4-carbaldehyde
  参考文献：
  名称：

  Pyrimidine Thioethers:  A Novel Class of HIV-1 Reverse Transcriptase Inhibitors with Activity Against BHAP-Resistant HIV

  摘要：

  A series of pyrimidine thioethers was synthesized and evaluated for inhibitory properties against wild-type HIV-1 reverse transcriptase (RT) and an RT carrying the resistance-conferring mutation P236L. Modifications of both the pyrimidine and the functionality attached through the thioether yielded several analogues, which demonstrated activity against both enzyme types, with IC50 values as low as 190 nM against wild-type and 66 nM against P236L RT. Evaluation of a select number of pyrimidine thioethers in cell culture showed that these compounds have excellent activity against HIV-1(IIIB)-WT and retain good activity against a laboratory-derived HIV-1(MF) delavirdine-resistant variant.

  DOI：

  10.1021/jm9800806
• 作为产物：
  描述：

  2,2-二乙氧基乙酸乙酯 在 sodium methylate 、 sodium 作用下， 反应 10.0h， 生成 6-(diethoxymethyl)-2-<(2-naphthalenylmethyl)thio>-4-pyrimidinol
  参考文献：
  名称：

  Pyrimidine Thioethers:  A Novel Class of HIV-1 Reverse Transcriptase Inhibitors with Activity Against BHAP-Resistant HIV

  摘要：

  A series of pyrimidine thioethers was synthesized and evaluated for inhibitory properties against wild-type HIV-1 reverse transcriptase (RT) and an RT carrying the resistance-conferring mutation P236L. Modifications of both the pyrimidine and the functionality attached through the thioether yielded several analogues, which demonstrated activity against both enzyme types, with IC50 values as low as 190 nM against wild-type and 66 nM against P236L RT. Evaluation of a select number of pyrimidine thioethers in cell culture showed that these compounds have excellent activity against HIV-1(IIIB)-WT and retain good activity against a laboratory-derived HIV-1(MF) delavirdine-resistant variant.

  DOI：

  10.1021/jm9800806

文献信息

• Alpha-substituted pyrimidine-thioalkyl and alkylether compounds as
  申请人：Pharmacia & Upjohn Company

  公开号：US06043248A1

  公开（公告）日：2000-03-28

  The subject invention relates to pyrimidine-thioalkyl and alkylether compounds of Formula (I) and pyrimidine-thioalkyl and alkylethers of Formula (IA), namely the compounds of Formula (I) where R.sub.4 is selected from the group consisitng of --H or --NR.sub.15 R.sub.16 where R.sub.15 is --H and R.sub.16 is --H, C.sub.1 -C.sub.6 alkyl, NH.sub.2 or R.sub.15 and R.sub.16 taken together with the --N form 1-pyrrolidino, 1-morpholino or 1-piperidino; and R.sub.6 is selected from the group consisting of --H, or halo (preferably --Cl); with the overall proviso that R.sub.4 and R.sub.6 are not both --H. The compounds of Formula (IA) are useful in the treatment of individuals who are HIV positive being inhibitors of viral reverse transcriptase. ##STR1##

  该发明涉及式(I)的嘧啶-硫代烷基和烷基醚化合物，以及式(IA)的嘧啶-硫代烷基和烷基醚化合物，即式(I)中R.sub.4选自--H或--NR.sub.15 R.sub.16组，其中R.sub.15为--H且R.sub.16为--H、C.sub.1-C.sub.6烷基、NH.sub.2或R.sub.15和R.sub.16连同--N形成1-吡咯烷基、1-吗啉基或1-哌啶基；以及R.sub.6选自--H或卤素（优选--Cl）的化合物组，总的限制条件是R.sub.4和R.sub.6不能同时为--H。式(IA)的化合物在治疗HIV阳性个体中具有抑制病毒逆转录酶的作用。
• [EN] ALPHA-SUBSTITUTED PYRIMIDINE-THIOALKYL AND ALKYLETHER COMPOUNDS AS INHIBITORS OF VIRAL REVERSE TRANSCRIPTASE<br/>[FR] UTILISATION DE COMPOSES A BASE DE PYRIMIDINE-THIOALKYLE A SUBSTITUTION alpha ET D'ALKYLETHER EN TANT QU'INHIBITEURS DE LA TRANSCRIPTASE INVERSE VIRALE
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：WO1996035678A1

  公开（公告）日：1996-11-14

  (EN) The subject invention relates to pyrimidine-thioalkyl and alkylether compounds of Formula (I) and pyrimidine-thioalkyl and alkylethers of Formula (IA), namely the compounds of Formula (I) where R4 is selected from the group consisitng of -H or-NR15R16 where R15 is -H and R16 is -H, C1-C6 alkyl, NH2 or R15 and R16 taken together with the -N form 1-pyrrolidino, 1-morpholino or 1-piperidino; and R6 is selected from the group consisting of -H, or halo (preferably -Cl); with the overall proviso that R4 and R6 are not both -H. The compounds of Formula (IA) are useful in the treatment of individuals who are HIV positive being inhibitors of viral reverse transcriptase.(FR) L'invention concerne des composés à base de pyrimidine-thioalkyle et d'alkyléther de formule (I) ainsi qu'à base de pyrimidine-thioalkyle et d'alkyléther de formule (IA), c'est-à-dire les composés de la formule (I) où R4 est choisi dans le groupe consistant en -H ou NR15R16, où R15 représente -H et R16 H, un alkyle en C1-C6, -NH2 ou bien R15 et R16, pris conjointement avec le -N, forment 1-pyrrolidino, 1-morpholino ou 1-piperidino et où R6 est choisi dans le groupe consistant en -H ou halo (de préférence -CI), à la condition générale que R4 et R6 ne représentent pas tous les deux -H. Les composés de la formule IA, étant des inhibiteurs de la transcriptase inverse virale, s'avèrent efficaces dans le traitement de personnes séropositives au VIH.

  本发明涉及式（I）的嘧啶硫代烷基和烷基醚化合物以及式（IA）的嘧啶硫代烷基和烷基醚化合物，即式（I）的化合物，其中R4选择自-H或-NR15R16的群组，其中R15为-H，R16为-H，C1-C6烷基，NH2或R15和R16共同与-N形成1-吡咯啉基，1-吗啉基或1-哌啶基；而R6选择自-H或卤（优选为-Cl）的群组，总的条件是R4和R6不同时为-H。式（IA）的化合物在治疗HIV阳性个体中是病毒反转录酶抑制剂。
• ALPHA-SUBSTITUTED PYRIMIDINE-THIOALKYL AND ALKYLETHER COMPOUNDS AS INHIBITORS OF VIRAL REVERSE TRANSCRIPTASE
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP0824524A1

  公开（公告）日：1998-02-25
• Pyrimidine Thioethers:  A Novel Class of HIV-1 Reverse Transcriptase Inhibitors with Activity Against BHAP-Resistant HIV
  作者：Richard A. Nugent、Stephen T. Schlachter、Michael J. Murphy、Gary J. Cleek、Toni J. Poel、Donn G. Wishka、David R. Graber、Yoshihiko Yagi、Barbara J. Keiser、Robert A. Olmsted、Laurie A. Kopta、Steven M. Swaney、Susan M. Poppe、Joel Morris、W. Gary Tarpley、Richard C. Thomas

  DOI：10.1021/jm9800806

  日期：1998.9.1

  A series of pyrimidine thioethers was synthesized and evaluated for inhibitory properties against wild-type HIV-1 reverse transcriptase (RT) and an RT carrying the resistance-conferring mutation P236L. Modifications of both the pyrimidine and the functionality attached through the thioether yielded several analogues, which demonstrated activity against both enzyme types, with IC50 values as low as 190 nM against wild-type and 66 nM against P236L RT. Evaluation of a select number of pyrimidine thioethers in cell culture showed that these compounds have excellent activity against HIV-1(IIIB)-WT and retain good activity against a laboratory-derived HIV-1(MF) delavirdine-resistant variant.