Drug repurposing against SARS-CoV-2 using computational approaches.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated a critical need for treatments to reduce morbidity and mortality associated with this disease. However, traditional drug development takes many years, which is not practical solution given the current pandemic. Therefore, a viable option is to repurpose existing drugs.

The first coordination complex of (5,6,7)-5-(furan-2-yl)-7-phenyl-4,5,6,7-tetra-hydro-[1,2,4]triazolo[1,5-]pyrimidin-6-amine with zinc(II) acetate-chloride.

The title complex, systematic name -poly[[[acetato-chlorido-zinc(II)]-μ-(5,6,7)-5-(furan-2-yl)-7-phenyl-4,5,6,7-tetra-hydro-[1,2,4]triazolo[1,5-]py-rimi-din-6-amine] monohydrate], {[Zn(CHO)Cl(CHNO)]·HO} , is the first coordination complex in which the neutral tetra-hydro-triazolo-pyrimidine derivative acts as bridging ligand between two zinc mol-ecules. As a result, polymeric chains of the coordination complex are found. The coordination of the zinc metal atom occurs with the lone pairs of the triazolo nitro-gen atom and amino group.

Computational study of novel inhibitory molecule, 1-(4-((2,3)-3-amino-2-hydroxy-4-phenylbutyl)piperazin-1-yl)-3-phenylurea, with high potential to competitively block ATP binding to the RNA dependent RNA polymerase of SARS-CoV-2 virus.

For coronaviruses, RNA-dependent RNA polymerase (RdRp) is an essential enzyme that catalyses the replication from RNA template and therefore remains an attractive therapeutic target for anti-COVID drug discovery. In the present study, we performed a comprehensive screening for 16,776 potential molecules from recently established drug libraries based on two important pharmacophores (3-amino-4-phenylbutan-2-ol and piperazine). Based on initial assessment, 4042 molecules were obtained suitable as drug candidates, which were following Lipinski's rule.

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds.

The unexpectedly uncatalyzed reaction between 2-amino-4-arylimidazoles, aromatic aldehydes and Meldrum's acid has selectively led to the corresponding Knoevenagel-Michael adducts containing a free amino group in the imidazole fragment. The adducts derived from Meldrum's acid have been smoothly converted into 1,7-diaryl-3-amino-6,7-dihydro-5-pyrrolo[1,2-]imidazol-5-ones and 3-(2-amino-4-aryl-1-imidazol-5-yl)-3-arylpropanoic acids. The interaction of 2-amino-4-arylimidazoles with aromatic aldehydes or isatins and acyclic methylene active compounds has led to the formation of pyrrolo[1,2-]imidazole-6-carbonitriles, pyrrolo[1,2-]imidazole-6-carboxylates and spiro[indoline-3,7'-pyrrolo[1,2-]imidazoles], which can be considered as the analogues of both 3,3'-spirooxindole and 2-aminoimidazole marine sponge alkaloids.

Dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-4-ones as a new class of CK2 inhibitors.

Identification of new small molecules inhibiting protein kinase CK2 is highly required for the study of this protein's functions in cell and for the further development of novel pharmaceuticals against a variety of disorders associated with CK2 activity. In this article, a virtual screening of a random small-molecule library was performed and 12 compounds were initially selected for biochemical tests toward CK2. Among them, the most active compound 1 ([Formula: see text]) belonged to dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-4-ones.

Crystal structure and Hirshfeld surface analysis of 7-eth-oxy-5-methyl-2-(pyridin-3-yl)-11,12-di-hydro-5,11-methano-[1,2,4]triazolo[1,5-][1,3,5]benzoxadiazo-cine.

The title compound, CHNO, was prepared by the reaction of 3-amino-5-(pyridin-3-yl)-1,2,4-triazole with acetone and 2-hy-droxy-3-eth-oxy-benzaldehyde. It crystallizes from ethanol in a tetra-gonal space group, with one mol-ecule in the asymmetric unit. The 1,2,4-triazole five-membered ring is planar (maximum deviation = 0.

An Overview of Currently Available Antimalarials.

Background: Despite the substantial progress over the time, malaria remains a major public health concern and causing hundreds of thousands of deaths. Resistance to the available antimalarial therapy increases threat to the global public health.

Objective: Overview of currently available antimalarials.

Self-assembled peptide nanoarchitectures: applications and future aspects.

Among the diversity of natural and synthetic compounds being studied and applied for human welfare, peptides able to develop nanostructures are currently under special attention of scientists. In this review, we focus on such properties of peptides and various kinds of intramolecular interactions allowing their ability to form different shapes of nanoassemblies. We have also discussed the applications of self-assembled peptides in various biomedical fields where they can be employed as cargo to target delivery of drugs, genes, in tissue engineering, regenerative medicines, and biosensors.

Three-component reaction of a 2-aminoazine, a 2-oxoaldehyde, and a cyclic 1,3-dicarbonyl compound for the synthesis of imidazo[1,2-a]azine derivatives.

A three-component reaction of a 2-aminoazine, a 2-oxoaldehyde, and a cyclic 1,3-dicarbonyl compound providing access toward a novel class of imidazo[1,2-a]azine derivatives was developed and studied. The scope of the process was thoroughly explored under three different reaction conditions resulting in the generation of a small library of title compounds and highlighting the possibility of case-specific approach.

The synthesis of low molecular weight pyrrolo[2,3-c]pyridine-7-one scaffold.

A facile method for the synthesis of substituted pyrrolo[2,3-c]pyridine-7-ones is developed that applies an acid-promoted intramolecular cyclization of 2-pyrrolecarboxylic acid amidoacetals as key step. The synthesis is easily scaled up to 1.5 mol quantity with no yield decrease.

Generation of 500-member library of 10-alkyl-2-R(1),3-R(2)-4,10-dihydrobenzo[4,5]imidazo[1,2-alpha]pyrimidin-4-ones.

Representative benzimidazopyrimidinones were previously reported to be intercalating antitumor agents. In this work, we used 2-substituted 4,10-dihydrobenzo [4,5]imidazo[1,2-alpha]pyrimidin-4-ones for their diversification by regioselective alkylation. Under the conditions established, the alkylation gave 10-alkyl derivatives which permitted the parallel generation of a 500-member library of the title compounds.

Diversification of a thieno[2,3-d]pyrimidin-4-one scaffold via regioselective alkylation reactions.

The 2-aryl-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-ones and 2-aryl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-ones have been diversified by alkylation reactions, applying benzylchlorides and N-substituted 2-chloroacetamides as alkylating agents. Under the found uniform conditions the substitution direction does not depend on the structure of the alkylating agent and gives monoalkylated products in high yields with simple workup. The alkylation of the 2,3-dihydropyrimidin-4(1H)-one derivatives proceeds onto the N1-position; however, in the case of pyrimidin-4(3H)-ones the O-alkylated products are formed selectively.

One hundred years of Meldrum's acid: advances in the synthesis of pyridine and pyrimidine derivatives.

A general review (138 references) focused on the recent advances in the application of Meldrum's acid reactivity for synthesis of diverse pyridine and pyrimidine derivatives, mostly small and drug-like molecules is presented.

Rapid three-step one-pot microwave-assisted synthesis of 2,5-dioxo-1,2,5,6,7,8-hexahydro-3-quinolinecarbonitrile library.

Many well-known drugs contain 2-pyridone and 2-quinolone scaffolds. In the current paper, a one-pot three-step microwave-assisted method for the synthesis of N1-substituted 2,5-dioxo-1,2,5,6,7,8-hexahydro-3-quinolinecarbonitrile derivatives was developed. Employing this protocol, we quickly generated 105 compounds library from 1,3-cyclohexanediones, dimethylformamide dimethylacetal, and various cyanacetamides.

Efficient ytterbium triflate catalyzed microwave-assisted synthesis of 3-acylacrylic acid building blocks.

The derivatives of 4-(hetero)aryl-4-oxobut-2-enoic acid are useful as building blocks in the synthesis of biologically active compounds. An efficient general protocol for the synthesis of these building blocks was developed. This method combines microwave assistance and ytterbium triflate catalyst and allows the fast preparation of the target acids starting from different (hetero)aromatic ketones and glyoxylic acid monohydrate giving pure products in 52-75% isolated yields.

An easy access to 2-Amino-5,6-dihydro-3H-pyrimidin-4-one building blocks: the reaction under conventional and microwave conditions.

A new one-stage fast multicomponent synthesis of title compounds leads to products in 21-55% isolated yields under both conventional and microwave conditions. The primary amino group in the building blocks can be easily acylated by various usual electophilic agents that can be utilized in the synthesis of diverse heterocylic compounds libraries.

Microwave-assisted scavenging of electrophiles utilizing polymer-supported sequestration reagents. Application to the synthesis of N3-acylated dihydropyrimidine libraries.

Different scavenging techniques using polymer-supported sequestration agents are described for the purification steps in the synthesis of N3-acylated dihydropyrimidines. For scavenging both excess anhydride and unwanted byproducts, polystyrene and silica supported diamines, aminomethyl-functionalized SynPhase Lanterns and diethylenetriamine StratoSpheres Plugs are used. In both synthesis and purification microwave flash heating was utilized, reducing reaction times from hours to minutes.

High-throughput synthesis of N3-acylated dihydropyrimidines combining microwave-assisted synthesis and scavenging techniques.

[reaction: see text] The solution-phase synthesis of N3-acylated dihydropyrimidines was achieved utilizing microwave flash heating both in the synthesis (acylation) and purification (scavenging) steps. Quenching times for excess anhydrides using polystyrene or silica-supported diamine sequestration reagents were reduced from several hours to minutes utilizing microwave irradiation. The use of water as sequestration agent, coupled with an efficient solid-phase extraction workup technique allowed the rapid generation of a 20-member library of N3-acylated dihydropyrimidines.