No abstract

A series of new derivatives of 3-phenylthiazolo[4,5-d]pyrimidine-2-thiones were synthesized by the cyclization of 4-amino-5-alkyl(aryl) carboxamido-2,3-dihydrothiazolo-2-thione with aromatic aldehydes. Amine moieties were substituted in position 7 of the obtained bicyclic compounds. The synthesized compounds were characterized by elemental analysis, IR, 1H-NMR, and 13C-NMR spectral data. Some of the newly synthesized compounds were selected by the U.S. National Cancer Institute for in vitro antitumor screening. The two compounds 3d 7-chloro-5-(4-fluorophenyl)-3-phenyl-4,5-dihydro-3H-thiazolo[4,5-d]pyrinimidine-2-thione and 4i 5-(2-chlorophenyl)-7-(4-fluorobenzylaxnlno)-3-phenyl-4,5-dihydro-3H-thiazolo[4,5-dipyrhflldlfle-2thione proved to be the most active in the present study and their antitumor activities against 60 human tumor cell lines were described.

Thiazolo[4,5-d]pyrimidine derivatives are considered potential therapeutic agents, particularly in the development of anticancer drugs. In this study, new 7-oxo-(2a-e), 7-chloro-(3a-e) and also three 7-amino-(4a-c) 5-trifluoromethyl-2-thioxo-thiazolo[4,5-d]pyrimidine derivatives have been synthesized and evaluated for their potential anticancer activity. These derivatives were characterized by spectroscopic methods and elemental analysis, and the single-crystal X-ray diffraction was further performed to confirm a 3D structure for compounds 2e and 4b. The antiproliferative activity evaluation of twelve new compounds was carried out on a variety of cell lines including four human cancer (A375, C32, DU145, MCF-7/WT) and two normal cell lines (CHO-K1 and HaCaT). Four of them (2b, 3b, 4b and 4c) were selected by the National Cancer Institute and evaluated for their in vitro anticancer activity using the NCI-60 screening program. 7-Chloro-3-phenyl-5-(trifluoromethyl)[1,3]thiazolo[4,5-d]pyrimidine-2(3H)-thione (3b) proved to be the most active among the newly synthesized compounds.

A number of derivatives of isoxazolo [4,3-d]pyrimidine and isoxazolo [4,5-d]pyrimidine were prepared with potential anticancer activity. Condensation of 4-amino-5-benzoyl-isoxazolo-3-carboxylic acid hydrazide with ethyl orthoformate and then with different amines gave a series of 3-benzoyl-7-oxo-7H-isoxazolo[4,3-d]pyrimidin-6-yl-aryliden-formamidine. A series of 5-aminomethyl-7-phenyl-isoxazolo[4,5-d]pyrimidine-3-carboxamide was obtained from 4-amino-5-benzoylisoxazole-3-carboxamide with acetonitrile, and chloroacetonitrile with gaseous hydrogen chloride. Some of these compounds were tested for their cytotoxic activity.

In the present study, using Thorpe's reaction with Gewald's modification, 4-acetylamino-5-acetyl or 5-benzoyl 3carboxamide compounds 3 or 4 were obtained. From these compounds, two series of compounds (5, 7, and 9 and 6, 8, and 10) were obtained with 98% hydrazine. Compounds 6, 7, 8, and 9 were then reacted with the appropriate aldehydes to afford a series of new isoxazole derivatives (11−18, 27−36, and 37−41) and the main compounds, 19−26 and 42−45, were isoxazolo[4,5e][1,2,4]triazepine derivatives. The anticarcinogenic activities of selected compounds were tested on six lines of cancer cells, and their activities were compared with the relevant concentrations of the anticarcinogenic drugs cisplatin and doxorubicin in IITD PAN. Several compounds were tested on 60 lines of cancer cells by the NCI (Bethesda, MD, USA). The cyclization of compound 12 into derivative 46 was also carried out. Compound 21 showed extremely high antitumor activity.