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Various novel thiopyrano[2,3-d][1,3]thiazol-2-one-6-carboxylic acids derivatives were synthesized in 54–86% yields via hetero-Diels–Alder reactions and related acylation-based tandem processes of 5-arylidene-4-thioxo-2-thiazolidinones with crotonic, propiolic, and cynnamic acids derivatives. Stereo- and regioselectivity of cycloaddition were investigated.

2-(4,5-Dihydropyrazol-1-yl)-thiazol-4-ones (2–5) have been synthesized starting from 3-phenyl-5-aryl-1-thiocarbamoyl-2-pyrazolines via [2+3]-cyclization with 2-bromopropionic acid, maleic anhydride, N-arylmaleimides, and aroylacrylic acids. The in vitro anticancer activity of 2a, 3a, 4a, 5b, and 5c were tested by the National Cancer Institute. Compounds 4a, 5b, and 5c demonstrated selective inhibition of leukemia cell lines growth at a single concentration (10−5 M). The screening of antiviral activity for a broad panel of viruses revealed that N-(4-methoxyphenyl)-2-{2-[5-(4-methoxyphenyl)-3-phenyl-4,5-dihydropyrazol-1-yl]-4-oxo-4,5-dihydrothiazol-5-yl}-acetamide 4a was highly active against Tacaribe TRVL 11 573 virus strain (EC50 = 0.71 μg/mL, selectivity index = 130).

The synthesis and evaluation of the anticancer activity of new acylated oximes derivatives of oleanolic acid with 4-thiazolidinone-3(5)-carboxylic acid moieties were described. Newly synthesized compounds were elucidated on the basis of elemental analyses and spectral data (IR, 1H, and 13C NMR). Anticancer activity of the tested compounds has been evaluated in vitro at National Cancer Institute (NCI) in which some structure activity relationships (SARs) were discussed. Among the tested compounds, 3-[(2,4-thiazolidinedione-5-ylidene)-carboxyimino]olean-12-en-28-oic acid methyl ester (IVm) was superior to other related compounds with mean values of pGI50 = 5.51/5.57, pTGI = 5.09/5.13, and pLC50 = 4.62/4.64, low toxicity and moderate activity level in vivo hollow fiber assay.

Utilization of 4-thioxo-2-(thi)oxothiazolidines in the synthesisof new fused thiopyrano[2,3- D][1,3]thiazolederivatives under Knoevenagel and HETERO-Diels-Alderreaction conditions has been studied.

The synthesis and evaluation of the anticancer activity of 3'-aryl-5'-arylidene-spiro[3H-indole-3,2'-thiazolidine]-2,4'(1H)-diones and spiro[3H-indole-3,2'-thi-azolidine]-2,4'(1H)-dione-3'-alkanoic acid esters were described. The structure of the compounds was determined by (1)H and (13)C NMR and their in vitro anticancer activity was tested in the National Cancer Institute. Among the tested compounds, (5'Z)-5'-(benzylidene)-3'-(4-chlorophenyl)spiro[3H-indole-3,2'-thia-zolidine]-2,4'(1H)-dione (IIa) and (5'Z)-3'-(4-chlorophenyl)-5'-[4-(1-methylethyl)-benzylidene]spiro[3H-indole-3,2'-thiazolidine]-2,4'(1H)-dione (IIb) were superior to other related compounds.

Antitumor screening of several novel 4-thiazolidinones with benzothiazole moiety has been performed. Reactions of (benzothiazole-2-yl)hydrazine with trithiocarbonyl diglycolic acid or 6-methyl-2-aminobenzothiazole with 2-carbethoxymethylthio-2-thiazoline-4-one have yielded starting 3- (1) or 2-substituted (11) 4-thiazolidinones which have been subsequently utilized in a Knoevenagel condensation for obtaining a series of 5-arylidene derivatives 2-10, 12-16. Compound 11 has been obtained alternatively by a counter synthesis method based on the reaction of 2-chloro-N-(6-methylbenzothiazol-2-yl)-acetamide and ammonium thiocyanate. The structures of compounds have been determined by (1)H, (13)C NMR, IR and X-ray analysis. In vitro anticancer activity of the synthesized compounds was tested by the National Cancer Institute and two (6, 16) of them has revealed the anticancer activity on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate and breast cancers cell lines. Among tested compounds, 2-{2-[3-(benzothiazol-2-ylamino)-4-oxo-2-thioxothiazolidin-5-ylidenemethyl]-4-chlorophenoxy}-N-(4-methoxyphenyl)-acetamide (6) was found to be the most active candidate with average logGI(50) and logTGI values -5.38 and -4.45 respectively.

Series of novel 5-arylidene-2-arylaminothiazol-4(5H)-ones and 2-aryl(benzyl)amino-1H-imidazol-4(5H)-ones were synthesized from appropriate 2-alkylthioazol-4-ones using nucleophilic substitution in position 2 by various anilines and benzylamines and Knoevenagel reaction. X-ray structural studies of 22 revealed the structure to be intermediate between amino and imino tautomeric forms. All the target compounds were evaluated for the anticancer activity in vitro in standard National Cancer Institute 60 cancer cell lines assay. Majority of compounds showed significant antitumor cytotoxicity effect at micromolar and submicromolar level (Mean Log GI50 ranges −5.77 to −4.35). Some of the most potent compounds, namely 10 and 13, possessed selectively high effect on all leukemia cell lines at submicromolar level (Mean Log GI50 [leukemia lines], respectively, −6.41 and −6.29), which are probably associated with immunosuppressive activity. Individual cancer cell lines sensitivity to synthesized compounds and SAR studies are discussed. COMPARE analysis allowed to disclose probable modes of anticancer action for synthesized compounds, in particular showed number of high correlations with activity patterns of alkylating agents (PCC ∼ 0.606–0.731).

To examine the anticancer activity several novel thiazolone-based compounds containing 5-aryl-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl framework were obtained. Reaction of 5-aryl-3-phenyl-4,5-dihydropyrazole with 4-thioxo-2-thiazolidinone or 2-carbethoxymethylthio-2-thiazoline-4-one yielded starting 4- (1 and 2) or 2-substituted (11 and 12) thiazolones which were utilized in Knoevenagel condensation for obtaining a series of 5-arylidene derivatives 3–10, 13–18. Alternatively 11, 12 and their 5-arylidene derivatives were synthesized by means of 3-phenyl-5-aryl-1-thiocarbamoyl-2-pyrazoline as S,N-binucleophile via [2 + 3]-cyclocondensation approach. The structures of compounds were determined by 1H, 13C NMR, LC–MS, EI-MS and X-ray analysis. The in vitro anticancer activity of synthesized compounds were tested by the National Cancer Institute and most of them displayed anticancer activity on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate and breast cancer cell lines. Relations between structure and activity are discussed, the most efficient anticancer compound 16 was found to be active with selective influence on colon cancer cell lines, especially on HT 29 (log GI50 = −6.37).

The use of 3-substituted-2-mercaptoacrylic acids, synthesized via hydrolysis of 5-ylidenerhodanines for the preparation of 2,3,5-trisubstituted-4-thiazolidinones via a new variant of the one-pot, three-component reaction has been studied.

The preparation of a series of thiopyrano[2,3-d][1,3]thiazole-6-carboxylic acids is achieved by hetero-Diels—Alder reaction of 5-arylideneisorhodanines with double and triple bond dienophiles.

A variety of new trisubstituted thiopyransthiazoles are synthesized via hetero-Diels—Alder reactions of 5-arylidene-4-thioxo-2-thiazolidinones with itaconic acid (II) or its imides, and screened as potential antitrypanosomal agents.

The synthesis and antitumor activity screening of novel 3-[2-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-4-oxo-4,5-dihydro-1,3-thiazol-5-ylidene]-2,3-dihydro-1H-indol-2-ones 1-23 and 3-(3,5-diarylpyrazol-1-yl)-2,3-dihydro-1H-indol-2-ones 24-39 are performed. In vitro anticancer activity of the synthesized compounds was tested by the National Cancer Institute. Most of them displayed anticancer activity on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancers cell lines. The structure-activity relationship is discussed. The most effective anticancer compound 10 was found to be active with mean GI₅₀ and TGI values of 0.071 μM and 0.76 μM, respectively. It demonstrated the highest antiproliferative influence on the non-small-cell lung cancer cell line HOP-92 (GI₅₀0.01 μM), colon cancer line HCT-116 (GI₅₀ = 0.018 μM), CNS cancer cell line SNB-75 (GI₅₀ = 0.0159 μM), ovarian cancer cell line NCI/ADR-RES (GI₅₀ = 0.0169 μM), and renal cancer cell line RXF 393 (GI₅₀ = 0.0197 μM).

To examine the anticancer activity several novel thiazolone-based compounds containing 5-aryl-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl framework were obtained. Reaction of 5-aryl-3-phenyl-4,5-dihydropyrazole with 4-thioxo-2-thiazolidinone or 2-carbethoxymethylthio-2-thiazoline-4-one yielded starting 4- (1 and 2) or 2-substituted (11 and 12) thiazolones which were utilized in Knoevenagel condensation for obtaining a series of 5-arylidene derivatives 3–10, 13–18. Alternatively 11, 12 and their 5-arylidene derivatives were synthesized by means of 3-phenyl-5-aryl-1-thiocarbamoyl-2-pyrazoline as S,N-binucleophile via [2 + 3]-cyclocondensation approach. The structures of compounds were determined by 1H, 13C NMR, LC–MS, EI-MS and X-ray analysis. The in vitro anticancer activity of synthesized compounds were tested by the National Cancer Institute and most of them displayed anticancer activity on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate and breast cancer cell lines. Relations between structure and activity are discussed, the most efficient anticancer compound 16 was found to be active with selective influence on colon cancer cell lines, especially on HT 29 (log GI50 = −6.37).