In continuation to our previous work, thiazolopyrimidines 2a-x were synthesized through intramolecular cyclization of 2-phenacylthio-dihydropyrimidine hydrobromides 1a-x using polyphosphoric acid. On the other hand, thiazolo[3,2-a]pyrimidine-3-one 3 was coupled with aryldiazonium salts or condensed with isatin to afford compounds 4a-c or 5, respectively. Chemical structure of the target compounds was substantiated by IR, FT-IR, 1H-, 13C and DEPT-13C-NMR, MS as well as microanalyses. Moreover, the lipophilicity of the target compounds as expressed from Clog P. The antimicrobial screening of the test compounds 2a-x, 4a-c and 5 revealed moderate activity in comparison to reference drugs. Compounds 2a-c, 2e, 2o and 2v showed a gradual increase in their anti-inflammatory activity reaching its maximum at 5 h compared to indomethacin. Furthermore, the analgesic activity of compounds 2a-c, 2e, 2o and 2v revealed a maximum activity after 5 h of injection compared to aspirin and the LD50 of compounds 2e and 2v were determined.

An olomoucine analogues of 2-[(1-substituted)-2,6-dioxo-2,3,6,7–tetrahydro-1H-purin-8-ylsulfanyl]-N-substituted acetamide 6a-g and 7a-g, 1-substituted-8-[2-(4-substituted phenyl)-2-oxoethylsulphanyl]-3,7-dihydro-1H-purine-2,6-diones 9a-g and 10a-g, 3-(2-substituted benzyl)-6-(4-substituted phenyl)-1H-thiazolo[2,3-f]purine-2,4-dione 11a-g and 12a-g and their isosteres 3-substituted benzyl-5-methyl-7-substituted-1H-pyrido[2,3-d]pyrimidine-2,4-dione 13a-c and 14a-c were designed and synthesized. The target compounds 11a-g and 12a-g were prepared by cyclodehydration of 9a-g and 10a-g in PPA, while 13a-c and 14a-c were synthesized by condensation of 6-amino-3-(2-substituted benzyl)-1H-pyrimidine-2,4-dione 1a or 1b and the appropriate acylacetone in glacial acetic acid. Structures of the new compounds were verified on the basis of their IR, 1H NMR, MS, HRMS and elemental analyses. The newly synthesized compounds were tested for their anticancer activity and most of the tested compounds showed good to excellent inhibition activity against the tested human breast cancer cell line MCF-7 in comparison to doxorubicin as a reference drug. KEYWORDS: olomoucine; cyclin-depenent kinase; synthesis; anticancer