2,2-Dichloro-N-[5-[2-[3-(4-methoxyphenyl)-5-phenyl-3,4-dihydro-2H-pyrazol-2-yl]-2-oxoethyl]sulfanyl-1,3,4-thiadiazol-2-yl]acetamide

Abstract

The pharmacophore hybridization approach is widely used for the design of drug-like small molecules with anticancer properties. In the present work, a “cost-effective” approach to the synthesis of the novel non-condensed pyrazoline-bearing hybrid molecule with 1,3,4-thiadiazole and dichloroacetic acid moieties is proposed. The 5-amino-1,3,4-thiadiazole-2-thiol was used as a starting reagent, and the synthetic strategy includes stepwise alkylation of the sulfur atom and acylation of the nitrogen atom to obtain the target title compound. The structure of the synthesized 2,2-dichloro-N-[5-[2-[3-(4-methoxyphenyl)-5-phenyl-3,4-dihydro-2H-pyrazol-2-yl]-2-oxoethyl]sulfanyl-1,3,4-thiadiazol-2-yl]acetamide (yield 90%) was confirmed by 1H, 13C, 2D NMR and LC-MS spectra. Anticancer activity in “60 lines screening” (NCI DTP protocol) was studied in vitro for the title compound.

rel-2-[4-Chloro-2-[(5R,6R,7S)-6-[5-(4-methoxyphenyl)-3-(2-naphthyl)-3,4-dihydropyrazole-2-carbonyl]-5-methyl-2-oxo-3,5,6,7-tetrahydrothiopyrano[2,3-d]thiazol-7-yl]phenoxy]acetic Acid

“…The structures of the synthesized compounds 2 and 3 were confirmed by 1 H, 13 C NMR, and LC-MS spectra (copies of the spectra are presented in the Supplementary Materials). In the NMR spectra, the signals of all hydrogen and carbon atoms were presented.…”

“…The elemental analyses (C, H, N) were performed using the Perkin-Elmer 2400 CHN analyzer (PerkinElmer, Waltham, MA, USA) and were within ±0.4% of the theoretical values. The 500 MHz 1 H and 100 MHz 13 C NMR spectra were recorded on a Varian Unity Plus 500 (500 MHz) spectrometer (Varian Inc., Paulo Alto, CA, USA). All spectra were recorded at room temperature, except where indicated otherwise, and were referenced internally to solvent reference frequencies.…”

“…Taking into account the abovementioned data, and due to our ongoing interest in pyrazoline-bearing molecules [7,12,13], we report the application of pyrazoline-containing dienophile to the construction of novel thiopyrano [2,3-d]thiazole via the hetero-Diels-Alder reaction. The structure characterization of the synthesized molecule, using NMR and LC-MS spectra and an in vitro anticancer activity evaluation, according to the "60 lines screening" algorithm (DTP NCI, USA), are also presented.…”

“…All presented in the molecule aromatic protons appeared in the relevant area. In the 13 C NMR spectrum of compound 2, the signals of the carbons of the CH 3 groups were observed at 17.8 ppm (C-5) and 55.1 ppm (methoxy). The carbons of the pyrazoline ring resonated at 41.6, 59.2, and 154.4 ppm.…”

3-(2-Diisopropylaminoethyl)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione

“…The current cancer chemotherapy includes the use of synthetic/semi-synthetic agents with an impact on a wide range of molecular targets; however, searching for novel chemotherapeutics is an important and topical issue-first of all, due to drug resistance [1]. Modern directions in anticancer medicinal chemistry are aiming to use small molecules that tend to be prepared following cost-effective approaches, which are at a lesser risk of degradation in vivo and are more permeable to tumor penetration [2][3][4][5][6][7].…”