Synthesis of novel uracil non-nucleoside derivatives as potential reverse transcriptase inhibitors of HIV-1.
ABSTRACT 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.
SourceAvailable from: Chidan Kumar C. S.[Show abstract] [Hide abstract]
ABSTRACT: In the title pyrimidine-2,4-dione derivative, C14H16N2O2S, the dihedral angle between the six-membered rings is 77.81 (10)°. The mol-ecule is twisted about the Cp-S (p = pyrimidine) bond, with a C-S-C-N torsion angle of -59.01 (17)°. An intramolecular C-H⋯S hydrogen bond generates an S(5) ring motif. In the crystal, bifurcated acceptor N-H⋯O and C-H⋯O hydrogen bonds generate inversion-related dimers incorporating R 2 (1)(9) and R 2 (2)(8) loops. These dimers are connected into a chain extending along the a-axis direction by a second pair of inversion-related N-H⋯O hydrogen bonds, forming another R 2 (2)(8) loop. The crystal structure is further stabilized by weak inter-molecular C-H⋯π inter-actions, generating a three-dimensional network.Acta Crystallographica Section E Structure Reports Online 07/2014; 70(Pt 7):o768-o769. DOI:10.1107/S1600536814013269 · 0.35 Impact Factor
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ABSTRACT: A convenient synthesis of certain novel 5,6- disubstituted 2-(substituted amino)alkylthiopyrimidin- 4(3H)-ones is reported. 5,6-Disubstituted-2-thiouracils were allowed to react with the appropriate (2-chloroethyl/ propyl) amine/imide to give the corresponding 5,6-disubstituted 2-(substituted amino)alkylthiopyrimidin-4(3H)-one derivatives in moderate yields. The antimicrobial potential of the target compounds was determined towards Grampositive bacteria (Staphylococus aureus, Bacillus subtilis, and Bacillus cereus) and pathogenic fungi (Candida albicans and Aspergillus niger). The obtained data were expressed as diameter of the growth inhibition zone and minimum inhibition concentration (MIC) for the test compounds. The most active compound exhibited dual antibacterial (against S. aureus) and antifungal (against C. albicans) effects with MIC value = 0.0524 lmol/cm3.Monatshefte fuer Chemie/Chemical Monthly 11/2014; 145(11):1825–1837. DOI:10.1007/s00706-014-1253-2 · 1.35 Impact Factor
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ABSTRACT: In the molecule of the title compound, C7H9ClN2O2, the conformation is determined by intramolecular C—H...O and C—H...Cl hydrogen bonds, which generate S(6) and S(5) ring motifs. The isopropyl group is almost perpendicular to the pyrimidine ring with torsion angles of 70.8 (3) and 56.0 (3)�. In the crystal, two inversion-related molecules are linked via a pair of N—H...O hydrogen bonds into R22(8) dimers; these dimers are connected into chains extending along the bc plane via an additional N—H...O hydrogen bond and weaker C—H...O hydrogen bonds. The crystal structure is further stabilized by a weak – interaction [3.6465 (10) A˚ ] between adjacent pyrimidine-dione rings arranged in a head-to-tail fashion, producing a three-dimensional network.Acta Crystallographica Section E Structure Reports Online 11/2014; E70(11):o1144-o1145. DOI:10.1107/S1600536814021382 · 0.35 Impact Factor