Β-amino Carbonyl Derivatives Research Articles

Synthesis, Characterization, Pharmacogenomics, and Molecular Simulation of Pyridinium Type of Ionic Liquids and Their Applications.

Substituted pyridinium bromides are prepared by conventional and solvent-free greener methods. The solvent-free solid-phase (greener) method is superior to the conventional method because of its nontoxic nature, simple reaction setup procedure, and twenty times less time consumption. Column chromatography and toxic organic solvents are avoided. Substituted pyridinium salts 1-2(a-c) show excellent catalytic response in the preparation of β-amino carbonyl derivatives using the conventional approach. Pharmacokinetics is very important in target validation and in shifting a lead compound into a drug. The physicochemical properties discussed here can be used effectively in the drug designing candidate, which is a cumbersome process in clinical research. In addition, molecular simulations are demonstrated, and compounds 1-2(a-c) possess the most potent VEGFR-2 kinase protein inhibitory activities, and most interestingly, compound 2a strongly binds and regulates the VEGFR-2 kinase activity in therapeutic approaches and cancer prevention.

Asymmetric synthesis of cyclic β-amino carbonyl derivatives by a formal [3 + 2] photocycloaddition.

Herein, a visible-light mediated strategy unlocking a family of cyclic β-amino carbonyl derivatives bearing three contiguous stereogenic centres is introduced. The overall reactivity relies on the performance of the substrate-catalyst complex to assist both the enantiocontrol and the photoredox tasks. This transformation led to an enantioselective [3 + 2] photocycloaddition between coordinated α,β-unsaturated acyl imidazoles and cyclopropylamine derivatives.

In vitro anticancer activity of thiazole based β-amino carbonyl derivatives against HCT116 and H1299 colon cancer cell lines; study of pharmacokinetics, physicochemical, medicinal properties and molecular docking analysis

The present study describes the synthesis and anticancer evaluation of certain substituted rac-(2S)-2-[(R)-[(4-substitutedphenyl){[4-(4-substitutedphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone derivatives. The in vitro anti-cancer assay indicating substituted β-amino carbonyl derivatives 4g and 4r are particularly active in both tests (HCT116 and H1299). The 4f, 4o , and 4t are the least functioning; 4m and 4n are marginally active; 4b and 4c are more cytotoxic when the growth inhibition percent is compared with standard drugs Camptothecin (CPT.), Acyclovir (ACV), Cisplatin (CDDP.), Vinblastine (VBL) and Trichothecene (TCT.). Among them, 2-((4- p -tosylthiazol-2-ylamino)(4-hydroxyphenyl)methyl) cyclohexanone 4u exhibits selective cytotoxicities for IC 50 µg/mL against HCT116 and H1299, respectively. Simulation of virtually designed 21 compounds has been studied for active binding sites of Crystal Structure of the Cancer Genomic DNA Mutator APOBEC3B (PDB ID- 5CQD) enzyme using molecular modelling of protein-ligand interactions. The in-depth sequencing studies reveal that the involvement of APOBEC3B in cancer mutagenesis. For comparison, the binding behaviour of known standard drugs has also studied. The new SwissADME web utensil that gives free access to a pool of quick yet reliable analytical models is presented for physicochemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry. Among them, in-house capable technique, for example, BOILED-Egg, iLOGP, and Bioavailability Radar, are readily available on the web.

Synthesis of novel β-amino carbonyl derivatives and their inhibition effects on some metabolic enzymes

In this study, we reported the synthesis, characterization and activity-structure relationship of novel β-amino carbonyl compounds. Some novel bis-β-amino carbonyl (4a-e) and mono-β-amino carbonyl (5a-e) compounds were synthesized by using CeCl3·7H2O catalyzed Mannich-type reaction. The title compounds were characterized by FTIR, elemental analysis, 13C NMR and 1H NMR techniques. In addition, the crystal and molecular structures of 5a, 5d and 5e were illuminated by single crystal X-ray diffraction. The activity-structure relationship was established by analyzing the enzyme activity of synthesized β-amino carbonyl compounds, which were effectively inhibited by human carbonic anhydrase I (hCA I), and II (hCA II) isoenzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). According to the activity-structure relationship, the Ki values of the β-amino carbonyl compounds were determined between 11.42 and 70.71 nM on hCA I, 28.66–77.59 nM on hCA II, 18.66–95.35 nM on AChE and 9.54–94.70 nM on BChE. We hope that these compounds may have promising new potentials in both CA isoenzymes AChE and BChE enzyme inhibitors.

Aqueous formic acid: an efficient, inexpensive and environmentally friendly catalyst for diastereoselective synthesis of β-amino carbonyl derivatives

In this article, we present a convenient and green method for synthesis of β-amino carbonyl compounds through ball-milling technique by using aqueous formic acid, which is an inexpensive and highly efficient catalyst. This multi-component reaction was done at room temperature with high anti-selectivity and easy workup. The use of solvent-free ball-milling technique helped to have high yields and more cleanness, besides omitting the need for solvent in this method.

Synthesis of β-amino carbonyl derivatives of coumarin and benzofuran and evaluation of their biological activity

A series of β-amino carbonyl compounds containing coumarin (4a–h) and benzofuran (6a–i) moieties was synthesized by a three component Mannich reaction of 3-acetyl-2H-chromen-2-one (1) or 1-(1-benzofuran-2-yl) ethanone (5) with p-substituted aromatic aldehydes (2a–g) and aromatic amines (3a–b) in the presence of cerric ammonium nitrate as a catalyst. The newly synthesized compounds were screened for antimicrobial and antioxidant activities. Compounds 4b, 4e, 4f, 6f, 6g, and 6i showed microbial inhibition with minimal inhibition concentration ranging between 0.040 and 0.500 mg/mL, compounds 4b, 4c, 6c, 6e, and 6i showed promising free radical scavenging activity and compounds 4b, 4f, 6c, 6d, and 6h showed good chelating ability with Fe2+ ions. The synthesized compounds were studied for docking on the enzyme, glucosamine-6-phosphate synthase to predict the binding affinity and orientation at the active site of the receptor.

Novel aryl β-aminocarbonyl derivatives as inhibitors of Trypanosoma cruzi trypanothione reductase: binding mode revised by docking and GRIND2-based 3D-QSAR procedures

Trypanothione reductase has long been investigated as a promising target for chemotherapeutic intervention in Chagas disease, since it is an enzyme of a unique metabolic pathway that is exclusively present in the pathogen but not in the human host, which has the analog Glutathione reductase. In spite of the present data-set includes a small number of compounds, a combined use of flexible docking, pharmacophore perception, ligand binding site prediction, and Grid-Independent Descriptors GRIND2-based 3D-Quantitative Structure-Activity Relationships (QSAR) procedures allowed us to rationalize the different biological activities of a series of 11 aryl β-aminocarbonyl derivatives, which are inhibitors of Trypanosoma cruzi trypanothione reductase (TcTR). Three QSAR models were built and validated using different alignments, which are based on docking with the TcTR crystal structure, pharmacophore, and molecular interaction fields. The high statistical significance of the models thus obtained assures the robustness of this second generation of GRIND descriptors here used, which were able to detect the most important residues of such enzyme for binding the aryl β-aminocarbonyl derivatives, besides to rationalize distances among them. Finally, a revised binding mode has been proposed for our inhibitors and independently supported by the different methodologies here used, allowing further optimization of the lead compounds with such combined structure- and ligand-based approaches in the fight against the Chagas disease.

Highly Efficient One-pot Synthesis, Antimicrobial and Docking Studies of Newer β-amino Carbonyl Derivatives Catalyzed by Silica Sulfuric Acid

Highly Efficient One-pot Synthesis, Antimicrobial and Docking Studies of Newer β-amino Carbonyl Derivatives Catalyzed by Silica Sulfuric Acid

ChemInform Abstract: Asymmetric Tandem Reactions: New Synthetic Strategies

AbstractReview: 23 refs.

Asymmetric tandem reactions: New synthetic strategies

The use of domino and multicomponent reactions in asymmetric synthesis is constantly increasing nowadays. This allows for the synthesis of complex molecules in a single synthetic sequence, usually with high atom economy. Herein, we report three examples of new asymmetric tandem reactions recently developed in our laboratories, giving rise to new families of enantiomerically enriched fluorinated and nonfluorinated heterocycles. Thus, 1,4-dihydropyridines (1,4-DHPs) bearing fluorinated substituents at C6 were assembled by means of a Hantzsch-type reaction; cyclic β-amino carbonyl derivatives were prepared using a cross-metathesis (CM)–intramolecular aza-Michael sequence; while fluorinated indolines were obtained, for the first time, in a tandem nucleophilic addition–intramolecular aromatic substitution.

ChemInform Abstract: Bisphosphine‐Catalyzed Mixed Double‐Michael Reactions: Asymmetric Synthesis of Oxazolidines, Thiazolidines, and Pyrrolidines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Bisphosphine-catalyzed mixed double-Michael reactions: asymmetric synthesis of oxazolidines, thiazolidines, and pyrrolidines.

Bisphosphine-catalyzed mixed double-Michael reactions have been developed to afford β-amino carbonyl derivatives of oxazolidines, thiozolidines, and pyrrolidines in excellent yields and with high diastereoselectivities. Efficient reactions between amino-acid-derived pronucleophiles, such as β-amino alcohols, β-amino thiols, and γ-amino diesters, as Michael donors and electron-deficient acetylenes, such as propiolates, acetylacetylene, and tosylacetylene, as Michael acceptors provided access to azolidines containing both diversity of substituents and asymmetry. This methodologythe first examples of mixed double-Michael reactions of acetylenesis operationally simple and involves mild conditions. Mechanistically, it constitutes a rare example of the anchimeric assistance of bisphosphines in organocatalysis.

One-pot synthesis of aza-Morita–Baylis–Hillman adducts from α-oxo ketene- S, S-acetals, arylaldehydes and nitriles

Promoted by TiCl 4, a series of α-(1,3-dithiolan-2-ylidene)-β-amino carbonyl derivatives––the aza-Morita–Baylis–Hillman adducts, have been synthesized from α-oxo cyclic ketene- S, S-acetals, arylaldehydes, and nitriles in good to excellent yields. A mechanism involving sequential Morita–Baylis–Hillman and Ritter reactions for this novel one-pot, three-component reaction is described.