One‐pot Synthesis of 1,2,3,4‐Tetrahydropyrimidin‐2(1H)‐thione Derivatives and their Biological Activity

Abstract

2‐Thioxo/oxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxylate derivatives 2a, 2b, 2c, 2d were prepared by the reaction of ethyl acetoacetate and thiourea or urea with aldehydes using NH4Cl as a catalyst. Compounds 2a and 2c reacted with mono and bihalogenated compounds such as ethyl iodide, chloroacetonitrile, epichlorohydrin, acetyl chloride, ethyl bromoacetate, chloroacetic acid, chloroacetylchloride, and/or oxalyl chloride to afford compounds 3, 4a, 4b, 5, 6a, 6b, 7, 8, 9 and 10, respectively. Compounds 2a, 2c, and 7 were allowed to react with p‐fluorobenzaldehyde to yield the corresponding products 11a, 11b, and 12, respectively. Oxidation of 2a and 2c gave 2b, 13a, 13b, 14, 15, 16 dependent on the oxidizing agent used. Vilsmeiere‐Haack formylation of 2a and 2b with POCl3/DMF afforded 17a and 17b. Chlorination of 2b and 2d gave the chlorinated derivative 18a and 18b, which reacted with thiourea to give thioureidopyrimidine 19a and 19b. Reactions of 2a with hydrazine monohydrate, semicarbazide hydrochloride, and sodium hydroxide gave compounds 20, 21, 22, respectively. The cytotoxicity and in vitro anticancer evaluation of some prepared compounds have been assessed against two different human tumor cell lines including breast adenocarcinoma MCF‐7 and human hepatocellular carcinoma HepG2. Antimicrobial and antioxidant activities of some compounds were investigated. The newly synthesized compounds were characterized by IR, 1H‐NMR, 13C‐NMR, and mass spectral data.

3D‐pharmacophore study molecular docking and synthesis of pyrido[2,3‐d]pyrimidine‐4(1H) dione derivatives with in vitro potential anticancer and antioxidant activities

“…In continuation of our program aiming to synthesize polyfunctional substituted heterocyclic compounds of potential biological activity, [ 3,4,8,17,18,23–29 ] the synthesis of poly‐functionalized 7‐amino‐5‐(4‐methoxyphenyl)‐2,4‐dioxo‐1,2,3,4‐tetrahydropyrido[2,3‐ d ]pyrimidine‐6‐carbonitrile ( 1a ) and 2‐amino‐4‐(4‐methoxyphenyl)‐5‐oxo‐5 H ‐dipyrido[1,2‐a:3′,2′‐ e ]pyrimidine‐3‐carbonitrile ( 1b ) was achieved via one‐pot multicomponent reactions of the barbituric acid and/or 3 H ‐pyrido [1,2‐ a ]pyrimidine‐2,4‐dione, [ 26 ] anisaldehyde, ammonium acetate and malononitrile or three‐component reactions of barbituric acid and/or 3 H ‐pyrido[1,2‐ a ]pyrimidine‐2,4‐dione, arylidine of malononitrile and ammonium acetate, under fusion at 150°C (Scheme 1).…”

Synthesis and Antioxidant Properties of Novel Pyrimidine-Containing Heterocycles

“…As a continuation of our previous work 2,20,21,25,26 on the utility of activated nitriles in the synthesis of a wide variety of heterocyclic systems, in this work we aimed to design and construct pyrimidine derivatives from relatively simple starting materials. Thus,3]dioxol-5-yl)-4-oxo-2-thioxo-1,2,3,4tetrahydropyrimidine-5-carbonitrile (1) was prepared by condensation of thiourea with ethyl 3-(benzo [d][1,3]dioxol-5yl)-2-cyanoacrylate in refluxing ethanol.…”

Utilization of Cyanoacetohydrazide and Oxadiazolyl Acetonitrile in the Synthesis of Some New Cytotoxic Heterocyclic Compounds

“…In the light of these facts, and as a continuation of our efforts towards synthesizing biologically active heterocyclic compounds especially those with antitumor activity [58][59][60][61][62], we planned to synthesize new hydrazide and 1,3,4-oxadiazole derivatives in the hope that new antitumor agents might be discovered. Hydrazides are very useful starting materials for the construction of several heterocyclic compounds such as 1,3,4-oxadiazoles [13], 1,3-thiazoles [14], 1,3,4-thiadiazoles [15], 1,2,4-triazoles [16] [18], pyrroles [19] and pyrazoles [20].…”

“…In the light of these facts, and as a continuation of our efforts towards synthesizing biologically active heterocyclic compounds especially those with antitumor activity [58][59][60][61][62], we planned to synthesize new hydrazide and 1,3,4-oxadiazole derivatives in the hope that new antitumor agents might be discovered. …”