- Synthesis and Antiviral Evaluation of 1-[(2-Phenoxyethyl)oxymethyl] and 6-(3,5-Dimethoxybenzyl) Analogues of HIV Drugs Emivirine and TNK-651
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Novel emivirine analogues 6a, b were synthesized by reacting chloromethyl ethyl ether with 5-ethyl/isopropyl-6-(3,5-dimethoxybenzyl)uracils 5e, f. On the other hand, A series of new TNK-651 analogues 10a-f substituted at N-1 with phenoxyethoxymethyl moiety was prepared on treatment of the corresponding uracils 5a-f with bis(phenoxyethoxy)methane (9). The newly synthesized non-nucleosides were tested for antiviral activity against wild type HIV-1 IIIB as well as the resistant strains N119 (Y181C), A17 (K103N+Y181C), and the triple mutant EFVR (K103R+V179D+P225H) in MT-4 cells. Most of the tested compounds showed good activities. Among them 6-(3,5-dimethylbenzyl)-5-ethyl-1-[(2-phenoxyethyl)oxymethyl]uracil (10c) and 6-(3,5-dimethylbenzyl)-5-isopropyl-1-[(2-phenoxyethyl)oxymethyl]uracil (10d) that showed inhibitory potency higher than emivirine against both wild type HIV-1 and the tested mutant strains, as well as higher activity than efavirenz against EFVR.
- El-Brollosy,Loddo
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p. 181 - 188
(2016/05/02)
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- Novel synthetic route for 5-substituted 6-arylmethylluracils from 2,4,6-trichloropyrimidines
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(Chemical Equation Presented) Treatment of 2,4,6-trichloropyrimidines (1a,b) with the sodium salt of benzyl cyanide derivatives (2a,b) afforded 5-substituted 4-aryl(cyanomethyl)-2,6-dichloropyrimidines (3a-f). Compounds 3a,b were alkylated with methyl iod
- Loksha, Yasser M.
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experimental part
p. 1296 - 1301
(2010/03/23)
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- Synthesis and anti-HIV-1 evaluation of new Sonogashira-modified emivirine (MKC-442) analogues
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The MKC-442 analogue 6-(3,5-dimethylbenzyl)-5-ethyluracil substituted with a (propargyloxo)-methyl group at N(1) has previously been found highly active against HIV-1. The C≡C bond in the substituent at N(1) is here utilized in a series of chemical reacti
- Danel, Krzysztof,Jorgensen, Per T.,Pedersen, Erik B.,La Colla, Paolo,Collu, Gabriella,Loddo, Roberta
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scheme or table
p. 1385 - 1403
(2009/10/16)
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- Pyrimidine acyclonucleoside derivatives, preparation method and use thereof
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The invention relates to a compound having general formula (I): wherein n is equal to 3; R1 is an ethyl or isopropyl group; each of the R2 groups is independently of each other a hydrogen atom, a C1-C3 alkyl group or a halogen atom; one of the R3 and R4 groups represents a hydrogen atom while the other of the R3 and R4 groups represents an OH or OR5 group, where R5 can be a C2-C7 acyl group, an alkyl(C1-C6)animo-carbonyl group, an aralkyl(C1-C6)aminocarbonyl optionally substituted on the aryl, an arylcarbonyl group optionally substituted or a heteroarylaminocarbonyl group. Said compound is particularly suitable as an antiviral agent and especially as an anti-HIV-1 agent.
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Page/Page column 20
(2010/02/12)
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- Regioselective alkylation and arylation at the 6-position of pyrimidine: Synthesis of 5-alkyl-6-arylmethyl-2,4-pyrimidinediones
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5-Alkyl-2,4,6-trichloropyrimidines reacted with various nucleophiles to afford the regioselectivity 6-substituted pyrimidines as the major products in good yields, which were transformed to 5-alkyl-6-arylmethyl-2,4- pyrimidinediones of a key intermediate
- Lee, Yeon Soo,Kim, Yong Hae
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p. 1503 - 1517
(2007/10/03)
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- Antiviral 2, 4-pyrimidinedione derivatives
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Novel 2,4-pyrimidinedione compounds, and pharmaceutically acceptable salts thereof which possess good antiviral activities, and specifically represented by the following formula(I): STR1 wherein: R 1 represents an unsubstituted or substituted allyl group represented by CH 2 CH CR 5 R 6 or an unsubstituted or substituted propargyl group represented by CH 2 C CR 7 wherein R 5, R 6 and R 7 are each independently a hydrogen atom; a methyl group optionally substituted with a halogen atom, or a C 1-10 carbonyloxy, hydroxy, azido, cyano, optionally substituted amino, optionally substituted phosphonyl, optionally substituted phenyl, C 3-10 heteroaryl, C 1-3 alkoxy or benzyloxy radical; a C 2-10 alkyl or alkenyl group; a cyclopropyl group; an optionally substituted phenyl group; a C 3-10 heteroaryl group; a C 1-10 ester group; or an optionally substituted C 1-10 alkylamide group;R 2 represents a halogen atom, an optionally substituted C 1-5 alkyl, C 3-6 cycloalkyl, C 2-8 alkenyl, C 2-8 alkynyl group or a benzyl group;R 3 and R 4 represent independently a hydrogen or halogen atom, or a hydroxy, C 1-3 alkyl, fluoromethyl, C 1-3 alkoxy, amino, C 2-6 alkylester or C 2-7 alkylamide group;A represents an oxygen or sulfur atom;Z represents an oxygen or sulfur atom; a carbonyl group; an amino group; or a methylene group optionally substituted with at least one selected from the group consisting of a halogen atom, and a cyano, hydroxy, azido, amino, C 1-3 alkylamide, C 1-4 ester, and nitro groups.
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- Synthesis and potent anti-HIV-1 activity of novel 6-benzyluracil analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine
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Ethyl 2-alkyl-4-aryl-3-oxobutyrates were synthesized from the corresponding arylacetonitriles and 2-brome esters. Condensation of the butyrates with thiourea followed by treatment with chloroacetic acid afforded the 5-alkyl-6-(arylmethyl)uracils. Condensa
- Danel, Krzysztof,Larsen, Erik,Pedersen, Erik B.,Vestergaard, Bent F.,Nielsen, Claus
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p. 2427 - 2431
(2007/10/03)
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