相似文献

1

9-{[3-fluoro-2-(hydroxymethyl)cyclopropylidene]methyl}adenines and -guanines. Synthesis and antiviral activity of all stereoisomers1.

J Med Chem. 2006 Oct 5;49(20):6120-8. doi: 10.1021/jm0607404.

2

Synthesis and antiviral activity of (Z)- and (E)-2,2-[bis(hydroxymethyl)cyclopropylidene]methylpurines and -pyrimidines: second-generation methylenecyclopropane analogues of nucleosides.

J Med Chem. 2004 Jan 29;47(3):566-75. doi: 10.1021/jm030316s.

3

(Z)- and (E)-2-((hydroxymethyl)cyclopropylidene)methyladenine and -guanine. New nucleoside analogues with a broad-spectrum antiviral activity.

J Med Chem. 1998 Jan 1;41(1):10-23. doi: 10.1021/jm9705723.

4

(Z)- and (E)-[2-Fluoro-2-(hydroxymethyl)cyclopropylidene]methylpurines and -pyrimidines, a new class of methylenecyclopropane analogues of nucleosides: synthesis and antiviral activity.

J Med Chem. 2004 Dec 30;47(27):6964-72. doi: 10.1021/jm040093l.

5

Synthesis of (Z)-(2,3-bis-hydroxymethyl)methylenecyclopropane analogues of purine nucleosides.

Nucleosides Nucleotides Nucleic Acids. 2003 Mar;22(3):265-74. doi: 10.1081/NCN-120021426.

6

Fluoroanalogues of anti-cytomegalovirus agent cyclopropavir: synthesis and antiviral activity of (E)- and (Z)-9-{[2,2-bis(hydroxymethyl)-3-fluorocyclopropylidene]methyl}-adenines and guanines.

Nucleosides Nucleotides Nucleic Acids. 2007;26(3):231-43. doi: 10.1080/15257770701257210.

7

Fluorinated methylenecyclopropane analogues of nucleosides. Synthesis and antiviral activity of (Z)- and (E)-9-{[(2-fluoromethyl-2-hydroxymethyl)-cyclopropylidene]methyl}adenine and -guanine.

Bioorg Med Chem. 2008 Mar 1;16(5):2148-55. doi: 10.1016/j.bmc.2007.11.082. Epub 2007 Dec 5.

8

(R)-(-)- and (S)-(+)-Synadenol: synthesis, absolute configuration, and enantioselectivity of antiviral effect.

J Med Chem. 1998 Dec 17;41(26):5257-64. doi: 10.1021/jm980323u.

9

Synthesis of (Z)- and (E)-9-[(2-hydroxyethylidene)cyclopropyl]adenine--new methylenecyclopropane analogues of adenosine and their substrate activity for adenosine deaminase.

Nucleosides Nucleotides Nucleic Acids. 2000 Jan-Feb;19(1-2):31-7. doi: 10.1080/15257770008032995.

10

(Z)- and (E)-2-(1,2-dihydroxyethyl)methylenecyclopropane analogues of 2'-deoxyadenosine and 2'-deoxyguanosine. Synthesis of all stereoisomers, absolute configuration, and antiviral activity.

J Med Chem. 2009 May 28;52(10):3397-407. doi: 10.1021/jm900126v.

引用本文的文献

1

Site-specific regulation of RNA editing with ribose-modified nucleoside analogs in ADAR guide strands.

Nucleic Acids Res. 2024 Jul 8;52(12):6733-6747. doi: 10.1093/nar/gkae461.

2

Status Presens of Antiviral Drugs And Strategies: Part I: DNA Viruses and Retroviruses.

Adv Antivir Drug Des. 2007;5:1-58. doi: 10.1016/S1075-8593(06)05001-5. Epub 2007 Sep 2.

3

Carba-cyclophellitols Are Neutral Retaining-Glucosidase Inhibitors.

J Am Chem Soc. 2017 May 17;139(19):6534-6537. doi: 10.1021/jacs.7b01773. Epub 2017 May 5.

4

Synthesis of ,-Dialkyl Adenine Nucleosides With In Situ Formed Hexaalkylphosphorus Triamides.

European J Org Chem. 2009 Jan 1;2009(1):152-159. doi: 10.1002/ejoc.200800752.

5

Synthesis and antiviral activities of methylenecyclopropane analogs with 6-alkoxy and 6-alkylthio substitutions that exhibit broad-spectrum antiviral activity against human herpesviruses.

Antimicrob Agents Chemother. 2013 Aug;57(8):3518-27. doi: 10.1128/AAC.00429-13. Epub 2013 May 13.

6

Phosphonate analogues of cyclopropavir phosphates and their E-isomers. Synthesis and antiviral activity.

Bioorg Med Chem. 2009 Jun 1;17(11):3892-9. doi: 10.1016/j.bmc.2009.04.020. Epub 2009 Apr 17.

7

(Z)- and (E)-2-(1,2-dihydroxyethyl)methylenecyclopropane analogues of 2'-deoxyadenosine and 2'-deoxyguanosine. Synthesis of all stereoisomers, absolute configuration, and antiviral activity.

J Med Chem. 2009 May 28;52(10):3397-407. doi: 10.1021/jm900126v.

8

Fluorinated methylenecyclopropane analogues of nucleosides. Synthesis and antiviral activity of (Z)- and (E)-9-{[(2-fluoromethyl-2-hydroxymethyl)-cyclopropylidene]methyl}adenine and -guanine.

Bioorg Med Chem. 2008 Mar 1;16(5):2148-55. doi: 10.1016/j.bmc.2007.11.082. Epub 2007 Dec 5.

本文引用的文献

1

A New Alkylation-Elimination Method for Synthesis of Antiviral Fluoromethylenecyclopropane Analogues of Nucleosides.

Tetrahedron. 2005 Jul 25;61(30):7112-7116. doi: 10.1016/j.tet.2005.05.054.

2

In vitro activity and mechanism of action of methylenecyclopropane analogs of nucleosides against herpesvirus replication.

Antimicrob Agents Chemother. 2005 Mar;49(3):1039-45. doi: 10.1128/AAC.49.3.1039-1045.2005.

3

Nucleotides and pronucleotides of 2,2-bis(hydroxymethyl)methylenecyclopropane analogues of purine nucleosides: synthesis and antiviral activity.

J Med Chem. 2005 Jan 13;48(1):91-9. doi: 10.1021/jm040149b.

4

(Z)- and (E)-[2-Fluoro-2-(hydroxymethyl)cyclopropylidene]methylpurines and -pyrimidines, a new class of methylenecyclopropane analogues of nucleosides: synthesis and antiviral activity.

J Med Chem. 2004 Dec 30;47(27):6964-72. doi: 10.1021/jm040093l.

5

Oral activity of a methylenecyclopropane analog, cyclopropavir, in animal models for cytomegalovirus infections.

Antimicrob Agents Chemother. 2004 Dec;48(12):4745-53. doi: 10.1128/AAC.48.12.4745-4753.2004.

6

Synthesis and antiviral activity of (Z)- and (E)-2,2-[bis(hydroxymethyl)cyclopropylidene]methylpurines and -pyrimidines: second-generation methylenecyclopropane analogues of nucleosides.

J Med Chem. 2004 Jan 29;47(3):566-75. doi: 10.1021/jm030316s.

7

Inhibition of human immunodeficiency virus reverse transcriptase by synadenol triphosphate and its E-isomer.

J Med Chem. 2003 Oct 23;46(22):4799-802. doi: 10.1021/jm030048y.

8

Methylene-gem-difluorocyclopropane analogues of nucleosides: synthesis, cyclopropene-methylenecyclopropane rearrangement, and biological activity.

J Med Chem. 2001 Nov 8;44(23):4019-22. doi: 10.1021/jm010191w.

9

Fluorinated nucleosides.

Carbohydr Res. 2000 Jul 10;327(1-2):87-105. doi: 10.1016/s0008-6215(00)00089-6.

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍。

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

文档翻译

学术文献翻译模型，支持多种主流文档格式。

9-{[3-氟-2-(羟甲基)环亚丙基]甲基}腺嘌呤和鸟嘌呤。所有立体异构体的合成与抗病毒活性1。

9-{[3-fluoro-2-(hydroxymethyl)cyclopropylidene]methyl}adenines and -guanines. Synthesis and antiviral activity of all stereoisomers1.

作者信息

Zhou Shaoman, Kern Earl R, Gullen Elizabeth, Cheng Yung-Chi, Drach John C, Tamiya Sadahiro, Mitsuya Hiroaki, Zemlicka Jiri

机构信息

Department of Chemistry, Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201-1379, USA.

出版信息

J Med Chem. 2006 Oct 5;49(20):6120-8. doi: 10.1021/jm0607404.

DOI:10.1021/jm0607404

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2562564/

Abstract

All stereoisomers of adenine and guanine methylene-3-fluoromethylenecyclopropane analogues of nucleosides 9a, 9b, 10a, 10b, 11a, 11b, 12a, and 12b were synthesized and their antiviral activities were evaluated. A highly convergent approach permitted the synthesis of all these analogues using a single intermediate 15. Reaction of aldehyde 13 with fluorotrichloromethane and tri-n-butylphosphine gave fluoroalkenes 14a+14b (83:17). Addition of carbene derived from ethyl diazoacetate gave cyclopropane 15 as the major product. Reduction (19), bromination (20), and phenylselenenylation (21), followed by Se oxidation and beta-elimination gave cis-methylenecyclopropane 22. Addition of bromine provided the reagent 23 for alkylation-elimination. Reaction of 23 with adenine led to an isomeric mixture 25a+26a that after deprotection afforded analogues 9a and 10a. The 2-amino-6-chloropurine furnished 25e+26e and after deblocking (9e and 10e) and hydrolysis gave targets 9b and 10b. Intermediate 15 provided, after debenzylation (27), 2-nitrophenylselenenylation (28), reduction (29), benzylation (30), and oxidation-elimination trans-methylenecyclopropane 31. Addition of bromine gave reagent 32. Further transformations followed the sequence outlined for analogues 9a, 9b, 10a, and 10b. Analogue 9b was effective against human cytomegalovirus (HCMV; Towne) with EC50 2.9 microM. The trans-isomer 10b inhibited AD169 strain of HCMV (EC50 15 microM) and the murine virus MCMV (EC50 2.5 microM). Compound 12a was effective against Epstein-Barr virus (EC50<0.03 microM). Analogue 9a inhibited varicella zoster virus (EC50 5.9 microM) and human immunodeficiency virus type 1 (EC50 5.2 microM). Analogues 9a, 10a, and 11a are moderate substrates for adenosine deaminase. The structure-activity relationships will be discussed in context with other methylenecyclopropane analogues.

摘要

合成了核苷9a、9b、10a、10b、11a、11b、12a和12b的腺嘌呤和鸟嘌呤亚甲基-3-氟亚甲基环丙烷类似物的所有立体异构体，并评估了它们的抗病毒活性。一种高度收敛的方法允许使用单一中间体15合成所有这些类似物。醛13与三氟氯甲烷和三正丁基膦反应生成氟代烯烃14a + 14b（83:17）。加入由重氮乙酸乙酯衍生的卡宾，得到环丙烷15作为主要产物。还原（19）、溴化（20）和苯硒基化（21），随后进行硒氧化和β-消除，得到顺式亚甲基环丙烷22。加入溴提供用于烷基化-消除的试剂23。23与腺嘌呤反应生成异构体混合物25a + 26a，脱保护后得到类似物9a和10a。2-氨基-6-氯嘌呤生成25e + 26e，脱保护（9e和10e）并水解后得到目标产物9b和10b。中间体15在脱苄基（27）、2-硝基苯硒基化（28）、还原（29）、苄基化（30）以及氧化-消除后得到反式亚甲基环丙烷31。加入溴得到试剂32。进一步的转化按照针对类似物9a、9b、10a和10b概述的顺序进行。类似物9b对人巨细胞病毒（HCMV；Towne株）有效，EC50为2.9微摩尔。反式异构体10b抑制HCMV的AD169株（EC50为15微摩尔）和鼠病毒MCMV（EC50为2.5微摩尔）。化合物12a对爱泼斯坦-巴尔病毒有效（EC50 < 0.03微摩尔）。类似物9a抑制水痘带状疱疹病毒（EC50为5.9微摩尔）和1型人类免疫缺陷病毒（EC50为5.2微摩尔）。类似物9a、10a和11a是腺苷脱氨酶的中度底物。将结合其他亚甲基环丙烷类似物讨论构效关系。