Synthesis and biological activity of N-acyl-5-bromanthranilic acids

Ten N-acyl-5-bromanthranilic acids have been obtained via acylation of 5-bromanthranilic acid with appropriate anhydrides. The antiinflammatory and antibacterial properties of the synthesized compounds have been evaluated. It is established that N-(o-anisoyl)-5-bromanthranilic acid possesses most pronounced antiinflammatory activity (49% inhibition of carrageenan induced paw edema in rat) and antimicrobial properties (MIC = 2.0 μg/ml with respect to St. aureus and E. coli). __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 8, pp. 12–14, August, 2006.     

Synthesis and biological activity of 5-phenylselenenyl-substituted pyrimidine nucleosides

Several 5-phenylselenenyl derivatives of pyrimidine nucleosides were synthesized by electrophilic addition of phenylselenenyl chloride to the nucleosides under basic conditions. With use of this route, 5-(phenylselenenyl)-6-azauracil was also prepared. These compounds may serve as inhibitors of thymidylate synthase, as potential antiviral and anticancer agents, and as versatile intermediates for the synthesis of 5- or 6-substituted nucleosides. 5-(Phenylselenenyl)arabinosyluracil (PSAU, 4) and the corresponding cytosine analogue (PSAC, 5) were poor inhibitors of a promyelocytic leukemia cell line that was arabinosylcytosine-resistant. PSAU and PSAC were significantly less active than ara-C against L1210 cells and were found to selectively interfere with the cellular uptake and/or phosphorylation of 2'-deoxycytidine and 2'-deoxyuridine in intact L1210 cells.     

Synthesis and biological activity of 5,11-methylenetetrahydro-5- deazahomofolic acid

The synthesis of 5,11-methylene-5-deazatetrahydrohomofolate (5), a stable, semirigid mimic of 5,10-methylenetetrahydrofolate (4) is reported as a potential inhibitor of thymidylate synthases (TS). The key intermediate 3-amino-1-oxo-tetrahydropyrimido[4,5-c] [2,6]naphthyridine (6) was obtained by the regiospecific cyclocondensation of 2,4,6-triaminopyrimidine with ethyl 1-benzyl-3-oxo-4-piperidinecarboxylate followed by halogenation (of the resulting lactam 9) and catalytic hydrogenolysis. Selective reduction of 6 followed by arylation with tert-butyl p-fluorobenzoate, saponification, and coupling with diethyl L-glutamate followed by saponification afforded the target compound 5. The title compound was tested as an inhibitor of the growth of Manca human lymphoma cells and also as an inhibitor of TS from Manca cells and Lactobacillus casei and was found to be inactive. In addition, compound 5 also failed to inhibit glycinamide ribonucleotide formyltransferase from L. casei and from Manca cells.     

Synthesis and biological activity of novel 5-fluoro-2'-deoxyuridine phosphoramidate prodrugs

A series of novel haloethyl and piperidyl phosphoramidate FdUMP prodrug analogues has been synthesized, and the growth inhibitory activity of these compounds has been evaluated against L1210 mouse leukemia cells. All compounds exhibited potent inhibition of L1210 cell proliferation with IC(50) values in the nanomolar range. Growth inhibition was reversed by the addition of 5 microM thymidine, suggesting a mechanism of action involving the intracellular release of FdUMP. (31)P NMR studies carried out on model haloethyl phosphoramidates confirm the release of nucleotide via cyclization of the phosphoramidate anion to the aziridinium ion intermediate followed by hydrolysis of the P-N bond. The data suggests that <50% of the prodrug is converted to FdUMP intracellularly by this pathway. Piperidyl phosphoramidate analogues are also converted to nucleotide intracellularly, presumably by the action of an endogenous phosphoramidase.     

Synthesis and biological activity of N(5)-β-oxyethylspinaceamines

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 23, No. 2, pp. 160–163, February, 1989.