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39 results on '"Loksha, Yasser M."'

5. Asymmetric Synthesis of Potential Precursors of the HIV Drug MC1220 and Its Analogues by Hydrogenation of (1-Arylvinyl)pyrimidines

Author

Loksha, Yasser M. and Pedersen, Erik B.

Abstract

Because MC1220 is a promising microbicide with anti-HIV-1 activity, the possibility for asymmetric synthesis of its potential precursors is explored. Here, we investigate asymmetric reduction of the vinyl double bond of 6-(1-arylvinyl)pyrimidine derivatives to their corresponding ethylidene analogues. Catalysts with ligands bearing trivalent phosphorus ligating the soft metals rhodium(I), ruthenium(II), or iridium(I) are used for asymmetric reduction of the vinyl derivatives 5a-e. The enantioselective reduction reaches 92% ee and about 71% conversion for reduction of the 6-(1-(3,5-dimethylphenyl)vinyl)pyrimidine derivative 5b using the asymmetric catalyst catASium M(R)Rh (7m). However, for the more sterically hindered double bond in the corresponding 2,6-difluorophenyl derivative 5e, the enantioselective reduction dropped to 30% ee and 14% conversion.

Published
2018
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7. Synthesis and Anti-HIV-1 Evaluation of Some Novel MC-1220 Analogs as Non-Nucleoside Reverse Transcriptase Inhibitors

Author

Loksha, Yasser M, Pedersen, Erik B, Loddo, Roberta, and La Colla, Paolo

Abstract

Some novel MC-1220 analogs were synthesized by condensation of 4,6-dichloro-N-methylpyrimidin-2-amine derivatives (1a,b and 15) and/or 4-chloro-6-methoxy-N,N,5-trimethylpyrimidin-2-amine (2a) with the sodium salt of 2,6-difluorophenylacetonitrile followed by treatment with aqueous sodium hydroxide in methanol, alkylation, reduction, halogenation, and/or acidic hydrolysis. All synthesized compounds were evaluated for their activity against HIV-1. The most active compound in this study was compound 7, which showed activity against HIV-1 comparable to that of MC-1220. The only difference in structure between compound 7 and MC-1220 is a fluoro atom instead of a CH3 group.

Published
2016
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33. Synthesis of 2-Hydroxymethyl-1H-imidazoles from 1,3-Dihydroimidazole-2-thiones.

Author

Loksha, Yasser M., El-Barbary, Ahmed A., El-Badawi, Mahmoud A., Nielsen, Claus, and Pedersen, Erik B.

Subjects
IMIDAZOLES, IMMUNOSUPPRESSIVE agents, SULFUR, SODIUM hydroxide, SODIUM compounds, CHEMICALS
Abstract

1,3-Dihydroimidazole-2-thiones 1a-d were desulfurized by hydrogen peroxide in either acid or neutral medium to afford 1Himidazoles 3a-d. Reaction of 3b,d with dimethylsulfamoyl chloride furnished N,N-dimethylsulfamoylimidazoles 5 and 6a,b. Lithiation of 5 and 6a,b followed by formylation and reduction yielded the 2-hydroxymethyl derivatives 7 and 8a,b. 4-Alkyl-5-cyclohexylmethyl-1H-imidazol-2-yl)methanols 9a,b were obtained by hydrolysis of 7 and 8a,b. [ABSTRACT FROM AUTHOR]

Published
2004

35. Novel synthetic route for 5substituted 6arylmethylluracils from 2,4,6trichloropyrimidines

Author

Loksha, Yasser M.

Abstract

Treatment of 2,4,6trichloropyrimidines 1a,b with the sodium salt of benzyl cyanide derivatives 2a,b afforded 5substituted 4arylcyanomethyl2,6dichloropyrimidines 3a–f. Compounds 3a,bwere alkylated with methyl iodide to furnish 41aryl1cyanoethyl2,6dichloropyrimidines 4a,b. Compounds 3a–fand 4a,bwere hydrolyzed with concentrated hydrochloric acid to afford 5substituted 6arylalkyluracils 5a–h. 5Bromo6arymethylluracils 6a–d were synthesized by bromination of 6arylmethylluracils 5a–d with Nbromosuccinimide NBS. Refluxing 22,6dichloro5ethylpyrimidin4yl23,5dimethylphenylacetonitrile 3f with sodium methoxide followed by oxidation afforded 3,5dimethylphenyl5ethyl2,6dimethoxypyrimidin4ylmethanone 7. Addition of methylmagnesium bromide to compound 7gave the tertiary alcohol derivative 8which was fluorinated by diethylaminosulfurtrifluoride and deprotected by trimethylsilyl iodide to furnish 613,5dimethylphenyl1fluoroethyl5ethylpyrimidine2,41H,3Hdione 12. J. Heterocyclic Chem., 2009.

Published
2009
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36. Studying the synthesis of 4tertbutyl1,3dihydroimidazol2ones and their corresponding thiones

Author

Loksha, Yasser M., Pedersen, Erik B., ElBarbary, Ahmed A., ElBadawi, Mahmoud A., and Nielsen, Claus

Abstract

4tertButyl1,3dihydroimidazol2ones and 1,3dihydroimidazol2thiones were synthesized from 1amino3,3dimethylbutanone and subjected to alkylation reactions. The latter compounds were Salkylated with iodoacetamide under alkaline conditions. The N1N3unsubstituted derivative was iodinated and subsequently alkylated with alkylation reagents which previously have been used for the synthesis of antiHTV active imidazoles. Unfortunately, the present products were devoid of activity against HTV.

Published
2003
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37. Synthesis of imidazoles as novel emivirine and SDABO analogues

Author

Loksha, Yasser M., Jørgensen, Per T., Pedersen, Erik B., ElBadawi, Mahmoud A., ElBarbary, Ahmed A., and Nielsen, Claus

Abstract

5Alkyl4benzyl1,3dihydroimidazol2ones 3ad and 5alkyl4benzyl1,3dihydroimidazole2thiones 7adwere prepared viaDakin West reaction on DLphenylalanine with the appropriate aliphatic acid anhydrides followed by hydrolysis and reaction with potassium cyanate or potassium thiocyanate. Compounds 3adwere alkylated with ethoxymethyl chloride to give the alkylated imidazoles 5adwhich were considered analogues of Emivirine with deletion of carbonyl group at the 4position. Alkylation of 7adafforded the corresponding Salkylated derivatives 8apwhich in a similar way were considered analogues of SDABO. However all the imidazole derivatives were devoid of activity against HIV.

Published
2002
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38. Synthesis of some novel 3,7dimethyl4Hpyrazolo5,1c1,2,4triazin4ones

Author

ElBarbary, Ahmed A., ElBadawi, Mahmoud A., and Loksha, Yasser M.

Abstract

Some novel 3,7dimethyl6Hpyrazolo5,1c1,2,4triazin4ones were prepared 3ag. Compounds 3a,bwere treated with hydrazines to afford various products 7a,b, 8a,b, 9 and lla,bdepending on the type of hydrazine derivative and reaction conditions. The benzoyloxyiminopyrazolo5,1c1,2,4triazines 13a,bwere synthesized by refluxing of compounds 3a,bwith hydroxylamine hydrochloride to afford the corresponding oxime derivatives followed by treatment with benzoyl chloride.

Published
2001
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39. Synthesis of 2-methylsulfanyl-1H-imidazoles as novel non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Author

Loksha YM, El-Badawi MA, El-Barbary AA, Pedersen EB, and Nielsen C

Subjects
Cell Line, HIV-1 drug effects, Humans, Imidazoles chemistry, Imidazoles pharmacology, Magnetic Resonance Spectroscopy, Reverse Transcriptase Inhibitors chemistry, Reverse Transcriptase Inhibitors pharmacology, Structure-Activity Relationship, Imidazoles chemical synthesis, Reverse Transcriptase Inhibitors chemical synthesis
Abstract

alpha-Aminoketone hydrochlorides 2a-d were synthesized by Dakin-West reaction from L-phenylalanine and L-cyclohexylalanine followed by hydrolysis in acidic medium. Treatment of 2a-d with aqueous potassium thiocyanate afforded 1, 3-imidazole-2-thiones 3a-d which were alkylated with methyl iodide to give 2-methylsulfanyl-1H-imidazoles 4a-d with 4-benzyl/4-cyclohexylmethyl and 5-ethyl/5-isopropyl substituents. Coupling of 4a-d with ethoxymethyl chloride or benzyloxymethyl chloride furnished N-1 5a-d and N-3 6a-h alkylated products. The synthesised compounds were tested for their activity against HIV-1. The most active compounds have a cyclohexylmethyl group in the 5-position of 6 and showed an activity against HIV-1 comparable to the activity of Nevirapine.

Published
2003
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