thiourea and pyrimidine

In this work, a one-pot, telescopic approach is described for the combinatorial library of thiazolidine-2-imines. The synthetic manipulation proceeds smoothly via the reaction of 2-aminopyridine/pyrazine/pyrimidine with substituted isothiocyanates followed by base catalyzed ring closure with 1,2-dibromoethane to obtain thiazolidine-2-imines with broad substrate scope and high functional group tolerance. The synthetic strategy merges well with the thiourea formation followed by base catalyzed ring closure reaction for the thiazolidine-2-imine synthesis in a more modular and straightforward approach. The synthetic procedure reported herein represents a cleaner route toward thiazolidine-2-imines as compared to traditional methodologies. Moreover, the biological significance of combinatorially synthesized thiazolidin-2-imines has been investigated for their use as possible inhibitors for acetyl cholinesterase through molecular docking studies.

Topics: Acetylcholinesterase; Aminopyridines; Anticonvulsants; Antineoplastic Agents; Antitubercular Agents; Catalysis; Cholinesterase Inhibitors; Ethylene Dibromide; Humans; Imines; Isothiocyanates; Microwaves; Pyrazines; Pyrimidines; Small Molecule Libraries; Structure-Activity Relationship; Thiazolidines; Thiourea

Histone lysine specific demethylase 1 (LSD1) was reported to be overexpressed in several human cancers and recognized as a promising anticancer drug target. In the current study, we designed and synthesized a novel series of pyrimidine-thiourea hybrids and evaluated their potential LSD1 inhibitory effect. One of the compounds, 6b, containing a terminal alkyne appendage, was shown to be the most potent and selective LSD1 inhibitor in vitro and exhibited strong cytotoxicity against LSD1 overexpressed gastric cancer cells. Compound 6b also showed marked inhibition of cell migration and invasion as well as significant in vivo tumor suppressing and antimetastasis role, without significant side effects by oral administration. Our findings indicate that the pyrimidine-thiourea-based LSD1 inactivator may serve as a leading compound targeting LSD1 overexpressed cancers.

Topics: Administration, Oral; Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Histone Demethylases; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Structure; Neoplasms, Experimental; Pyrimidines; Structure-Activity Relationship; Thiourea

An enantioselective Biginelli reaction has been developed by using a bifunctional primary amine-thiourea-TfOH (BPAT·TfOH) as a chiral phase-transfer catalyst and t-BuNH(2)·TFA as an additive in saturated brine at room temperature. The corresponding dihydropyrimidines were obtained in moderate-to-good yields with up to 99% ee under mild conditions. A plausible transition state has been proposed to explain the origin of the activation and the asymmetric induction.

Topics: Amines; Catalysis; Hydrogenation; Molecular Structure; Pyrimidines; Stereoisomerism; Thiourea; Trifluoroacetic Acid

A series of substituted acyl(thio)urea and 2H-1,2,4-thiadiazolo [2,3-a] pyrimidine derivatives were prepared and both of their cell culture and enzymatic activity toward influenza virus were tested. Their in vitro neuraminidase inhibitory activities were in good agreement with the corresponding activities in cultured cells and they were evaluated as potent neuraminidase inhibitors. Of the analogues that demonstrated IC(50)s<0.1microM, 16 and 60 were further investigated as candidates with the most potential for future development. The molecular docking work of the representative compound was described to provide more insight into their mechanism of action and further rationalize the observations of this new series herein, which represents a novel class of highly potent and selective inhibitors of influenza virus.

Topics: Animals; Antiviral Agents; Cell Line; Dogs; Enzyme Inhibitors; Humans; Influenza, Human; Inhibitory Concentration 50; Kidney; Models, Chemical; Molecular Structure; Neuraminidase; Orthomyxoviridae; Pyrimidines; Structure-Activity Relationship; Thiourea

Topics: Goiter; Humans; Pyrimidines; Thiourea; Thyroid Gland