Synthesis of Novel MKC-442 Analogues with Potent Activities against HIV-1

El‐Brollosy, Nasser R.; Pedersen, Erik B.; Nielsen, Claus

doi:10.1002/ardp.200300742

Cited by 17 publications

(13 citation statements)

References 23 publications

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“…It showed higher antiviral activity against HIV-1 wild type and greater tolerance to the presence of the mutated HIV strains than Emivirine, due to binding of the two methyl substituents in two hydrophobic pockets in the NNRTI-binding site of RT as revealed by X-ray crystallography [13]. In an effort to improve the activity against HIV-1 wild type and NNRTI resistant mutants, and as a part of our interest in the chemistry of NNRTIs [15][16][17][18][19][20][21][22][23][24][25], the present study describes synthesis and antiviral evaluation of novel non-nucleosides analogues of emivirine and GCA-186 with a N-1 cyclopropylmethoxymethyl substituent. Also, a series of TNK-651 analogues substituted at N-1 with 2-phenylethyloxymethy and 3-phenylprop-1-yloxymethyl moieties has been investigated.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Uracil Non‐Nucleoside Derivatives as Potential Reverse Transcriptase Inhibitors of HIV‐1

El‐Brollosy¹,

Al‐Deeb

El-Emam

et al. 2009

Archiv der Pharmazie

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Novel emivirine and TNK-651 analogues 5a-d were synthesized by reaction of chloromethyl ethyl ether and / or benzyl chloromethyl ether, respectively, with uracils having 5-ethyl and 6-(4-methylbenzyl) or 6-(3,4-dimethoxybenzyl) substituents. A series of new uracil non-nucleosides substituted at N-1 with cyclopropylmethyloxymethyl 9a-d, 2-phenylethyloxymethyl 9e-h, and 3-phenylprop-1-yloxymethyl 9i-l were prepared on treatment of the corresponding uracils with the appropriate acetals 8a-c. Some of the tested compounds showed good activity against HIV-1 wild type. Among them, 1-cyclopropylmethyloxymethyl-5-ethyl-6-(3,5-dimethylbenzyl)uracil 9c and 5-ethyl-6-(3,5-dimethylbenzyl)-1-(2-phenylethyloxymethyl)uracil 9g showed inhibitory potency equally to emivirine against HIV-1 wild type. Furthermore, compounds 9c and 9g showed marginal better activity against NNRTI resistant mutants than emivirine.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Uracil Non‐Nucleoside Derivatives as Potential Reverse Transcriptase Inhibitors of HIV‐1

El‐Brollosy¹,

Al‐Deeb

El-Emam

et al. 2009

Archiv der Pharmazie

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“…The acetals 5bϪh have been developed recently in our group to produce active Emivirine analogues against HIV-1 in the near picomolar range [7,14,15]. Bis(indan-1-yloxy)methane (5h) was prepared by reacting 1-indanol with dibromo-methane in refluxing anhydrous benzene in the presence of potassium hydroxide and tetrabutylammonium bromide.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis of 6‐(3,5‐Dichlorobenzyl) Derivatives as Isosteric Analogues of the HIV Drug 6‐(3,5‐Dimethylbenzyl)‐1‐(ethoxymethyl)‐5‐isopropyluracil (GCA‐186)

Sørensen

El‐Brollosy

Jørgensen

et al. 2005

Archiv der Pharmazie

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The HIV-1 inhibitors described in this paper is closely related to 6-(3,5-dimethylbenzyl)-1-(ethoxy methyl)-5-isopropyluracil (GCA-186) an anti-HIV-1 drug that is highly active against both wild type and mutated HIV-1 strains. The two methyl groups on the 6-benzyl moiety have been shown to improve the binding stability of the drug to the NNRTI-binding site in reverse transcriptase of drug mediated mutant HIV-1 viruses. The methyl groups are replaced with isosteric chloro-atoms to avoid metabolism due to the two methyl groups. However, the isosteric chloro derivatives show tenfold less activity against HIV-1 than their corresponding methyl derivatives. The synthesis and the antiviral activities of the corresponding 1-(allyloxy- and indanyloxy)methyl-6-(3,5-dichlorobenzyl)-5-ethyluracil derivatives are also reported.

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“…We found it of interest to evaluate the antimicrobial activity for such pyrimidine derivatives. In the present work, and as a part of our continuing interest in the chemistry of pyrimidines [30,34,35,36,37,38,39,40,41,42], the synthesis and antimicrobial evaluation of some novel 2-(substituted amino)alkylthiopyrimidin-4(3 H )-one derivatives have been investigated.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel 2-(Substituted amino)alkylthiopyrimidin-4(3H)-ones as Potential Antimicrobial Agents

et al. 2013

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5-Alkyl-6-(substituted benzyl)-2-thiouracils 3a,c were reacted with (2-chloroethyl) diethylamine hydrochloride to afford the corresponding 2-(2-diethylamino)ethylthiopyrimidin-4(3H)-ones 4a,b. Reaction of 3a-c with N-(2-chloroethyl)pyrrolidine hydrochloride and/or N-(2-chloroethyl) 3a, 3b, 4a, 5a, 5b, 6d, 6f, 7b and 7d, whereas compounds 4b, 5b, 5c, 6a, 6b and 6f exhibited the best antifungal activity.

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Synthesis of Novel MKC-442 Analogues with Potent Activities against HIV-1

Cited by 17 publications

References 23 publications

Synthesis of Novel Uracil Non‐Nucleoside Derivatives as Potential Reverse Transcriptase Inhibitors of HIV‐1

Synthesis of Novel Uracil Non‐Nucleoside Derivatives as Potential Reverse Transcriptase Inhibitors of HIV‐1

Synthesis of 6‐(3,5‐Dichlorobenzyl) Derivatives as Isosteric Analogues of the HIV Drug 6‐(3,5‐Dimethylbenzyl)‐1‐(ethoxymethyl)‐5‐isopropyluracil (GCA‐186)

Synthesis of Novel 2-(Substituted amino)alkylthiopyrimidin-4(3H)-ones as Potential Antimicrobial Agents

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