From cycloheptathiophene-3-carboxamide to oxazinone-based derivatives as allosteric HIV-1 ribonuclease H inhibitors.
Anti-HIV Agents
/ chemical synthesis
Cell Line
Dose-Response Relationship, Drug
HIV
/ drug effects
Humans
Molecular Docking Simulation
Molecular Structure
Oxazines
/ chemical synthesis
Reverse Transcriptase Inhibitors
/ chemical synthesis
Ribonuclease H, Human Immunodeficiency Virus
/ antagonists & inhibitors
Structure-Activity Relationship
Thiophenes
/ chemical synthesis
Allosteric inhibitors
HIV-1 ribonuclease H
antiviral agents
thieno[2,3-d][1,3]oxazin-4-one derivatives
Journal
Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
entrez:
27
10
2018
pubmed:
27
10
2018
medline:
10
11
2018
Statut:
ppublish
Résumé
The paper focussed on a step-by-step structural modification of a cycloheptathiophene-3-carboxamide derivative recently identified by us as reverse transcriptase (RT)-associated ribonuclease H (RNase H) inhibitor. In particular, its conversion to a 2-aryl-cycloheptathienoozaxinone derivative and the successive thorough exploration of both 2-aromatic and cycloheptathieno moieties led to identify oxazinone-based compounds as new anti-RNase H chemotypes. The presence of the catechol moiety at the C-2 position of the scaffold emerged as critical to achieve potent anti-RNase H activity, which also encompassed anti-RNA dependent DNA polymerase (RDDP) activity for the tricyclic derivatives. Benzothienooxazinone derivative 22 resulted the most potent dual inhibitor exhibiting IC
Identifiants
pubmed: 30362381
doi: 10.1080/14756366.2018.1523901
pmc: PMC6211256
doi:
Substances chimiques
Anti-HIV Agents
0
Oxazines
0
Reverse Transcriptase Inhibitors
0
Thiophenes
0
Ribonuclease H, Human Immunodeficiency Virus
EC 3.1.26.4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
55-74Références
J Biol Chem. 2000 May 12;275(19):14316-20
pubmed: 10799511
J Med Chem. 2010 Apr 8;53(7):2719-40
pubmed: 20131845
Methods Enzymol. 1995;262:130-44
pubmed: 8594344
Chembiochem. 2016 Apr 15;17(8):683-8
pubmed: 26946324
AIDS. 2014 May 15;28(8):1193-202
pubmed: 24556869
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
pubmed: 10592235
Future Med Chem. 2010 Jul;2(7):1161-80
pubmed: 21426162
Chembiochem. 2017 Feb 16;18(4):374-377
pubmed: 27992102
Nat Struct Biol. 1995 Apr;2(4):293-302
pubmed: 7540934
J Virol Methods. 1988 Aug;20(4):309-21
pubmed: 2460479
PLoS One. 2016 Jan 22;11(1):e0147225
pubmed: 26800261
Nature. 2014 Sep 25;513(7519):481-3
pubmed: 25254460
ACS Chem Biol. 2008 Oct 17;3(10):635-44
pubmed: 18831589
J Med Chem. 2014 Apr 24;57(8):3223-34
pubmed: 24684270
Org Lett. 2014 Sep 5;16(17):4662-5
pubmed: 25157475
Bioorg Med Chem Lett. 2005 Aug 15;15(16):3763-6
pubmed: 16005212
Antimicrob Agents Chemother. 2014 Jul;58(7):4086-93
pubmed: 24798282
ChemMedChem. 2013 Dec;8(12):1941-53
pubmed: 24150998
Methods Mol Biol. 2008;426:299-318
pubmed: 18542872
Antiviral Res. 2005 Feb;65(2):117-24
pubmed: 15708638
Antimicrob Agents Chemother. 2014 Oct;58(10):6101-10
pubmed: 25092689
J Med Chem. 2016 Apr 14;59(7):2849-78
pubmed: 26509831
ACS Chem Biol. 2006 Dec 20;1(11):702-12
pubmed: 17184135
Antimicrob Agents Chemother. 2010 Sep;54(9):3913-21
pubmed: 20547794
J Infect Dis. 2017 Mar 15;215(6):920-927
pubmed: 28453836
Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1466-71
pubmed: 18230722
Nucleic Acids Res. 2016 Mar 18;44(5):2310-22
pubmed: 26850643
ChemMedChem. 2016 Aug 19;11(16):1709-20
pubmed: 26990134
Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10548-53
pubmed: 15249669
Curr Med Chem. 2018;25(14):1682-1702
pubmed: 28088905
J Med Chem. 2016 Sep 8;59(17):7699-718
pubmed: 27046062
Eur J Med Chem. 2012 Apr;50:216-29
pubmed: 22361685
J Chem Inf Model. 2011 Aug 22;51(8):1986-98
pubmed: 21714567
J Med Chem. 2017 Jun 22;60(12):5045-5056
pubmed: 28525279
Future Med Chem. 2013 Dec;5(18):2127-39
pubmed: 24261890
J Med Chem. 2015 Feb 26;58(4):1915-28
pubmed: 25629256
Nucleic Acids Res. 2014 Jul;42(12):8125-37
pubmed: 24880687
Methods Enzymol. 1982;87:500-9
pubmed: 6757651
Chemistry. 2011 Oct 24;17(44):12246-9
pubmed: 21956858
Org Lett. 2012 Apr 6;14(7):1684-7
pubmed: 22404493
J Med Chem. 2015 May 14;58(9):3830-42
pubmed: 25856229
Nat Protoc. 2008;3(3):427-34
pubmed: 18323814
Pathog Dis. 2017 Aug 31;75(6):
pubmed: 28859311
Medchemcomm. 2018 Feb 1;9(3):562-575
pubmed: 30108947
J Comput Chem. 2005 Jul 15;26(9):915-31
pubmed: 15841474
Bioorg Med Chem. 2014 Jul 1;22(13):3449-54
pubmed: 24844756
Antivir Chem Chemother. 2014 Jan 29;23(4):129-44
pubmed: 24150519
J Med Chem. 2013 Mar 28;56(6):2606-18
pubmed: 23445496
ChemMedChem. 2011 Jul 4;6(7):1249-57
pubmed: 21567967
J Biomol Screen. 2006 Oct;11(7):854-63
pubmed: 16943390
Nat Struct Mol Biol. 2013 Feb;20(2):230-236
pubmed: 23314251
J Med Chem. 2013 Dec 27;56(24):10118-31
pubmed: 24313730
Antiviral Res. 2016 Oct;134:236-243
pubmed: 27659398
J Chem Inf Model. 2015 Nov 23;55(11):2324-37
pubmed: 26479676
HLA. 2016 Oct;88(4):155-63
pubmed: 27620852
Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):507-512
pubmed: 29295939
J Immunol. 2016 Jul 15;197(2):407-17
pubmed: 27382129
Acc Chem Res. 2000 Dec;33(12):889-97
pubmed: 11123888
Eur J Med Chem. 2015 Mar 26;93:452-60
pubmed: 25728026
Structure. 2009 Dec 9;17(12):1625-1635
pubmed: 20004166
J Nat Prod. 2016 Mar 25;79(3):616-28
pubmed: 26900761
Structure. 2000 Oct 15;8(10):1089-94
pubmed: 11080630
Eur J Med Chem. 2018 Aug 5;156:302-303
pubmed: 30007243
ChemMedChem. 2010 Nov 8;5(11):1880-92
pubmed: 20928882