Synthesis and bioactivity of new analogue of Bicyclic 1-Azafagomine

New (S)-(1,2,3,6-tetrahydropyridazin-3-yl)methanol was synthesized by Lewis acid catalyzed and self-assembled Diels-Alder (LACASA-DA) cycloaddition reaction using (S)-BINOL as a chiral inductor. The N-2 pyridazine position was protected, the hydroxyl group was carbonylated to form the new bicyclic structure. The protective group was removed and the double bond was dihydroxylated leading to the target compound. Removal of the protective group was performed using a newly found ecofriendly catalyst for N-Boc deprotection. The final iminosugar derivative 7 and all newly synthesized intermediates, were investigated against S. aureus and E. coli bacteria and were found to show promising activity against both gram-positive and gram-negative bacteria.- (undefined

Synthesis of 4,5-disubstituted-2-thioxo-1,2,3,4-tetrahydropyrimidines and investigation of their acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase I/II inhibitory and antioxidant activities.

A series of tetrahydropyrimidinethiones were synthesized from thiourea, β-diketones and aromatic aldehydes, such as p-tolualdehyde, p-anisaldehyde, o-tolualdehyde, salicylaldehyde and benzaldehyde. These cyclic thioureas showed good inhibitory action against acetylcholine esterase (AChE), butyrylcholine esterase (BChE), and human (h) carbonic anhydrase (CA) isoforms I and II. AChE and BChE inhibitions were in the range of 6.11-16.13 and 6.76-15.68 nM, respectively. hCA I and II were effectively inhibited by these compounds, with Ki values in the range of 47.40-76.06 nM for hCA I, and of 30.63-76.06 nM for hCA II, respectively. The antioxidant activity of the cyclic thioureas was investigated by using different in vitro antioxidant assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH·) radical scavenging, Cu2+ and Fe3+ reducing, and Fe2+ chelating activities

Crystal structure and Hirshfeld surface analysis of 2-(4-amino-6-phenyl-1,2,5,6-tetrahydro-1,3,5-triazin-2-ylidene)malononitrile dimethylformamide hemisolvate

The title compound, 2C(12)H(10)N(6)center dot C3H7NO, crystallizes as a racemate in the monoclinic P2(1)/c space group with two independent molecules (I and II) and one dimethylformamide solvent molecule in the asymmetric unit. Both molecules (I and II) have chiral centers at the carbon atoms where the triazine rings of molecules I and II are attached to the phenyl ring. In the crystal, molecules I and II are linked by intermolecular N-H center dot center dot center dot N, N-H center dot center dot center dot O and C-H center dot center dot center dot N hydrogen bonds through the solvent dimethylformamide molecule into layers parallel to (001). In addition, C-H center dot center dot center dot pi interactions also connect adjacent molecules into layers parallel to (001). The stability of the molecular packing is ensured by van derWaals interactions between the layers. The Hirshfeld surface analysis indicates that N center dot center dot center dot H/H center dot center dot center dot N (38.3% for I; 35.0% for II), H center dot center dot center dot H (28.2% for I; 27.0% for II) and C center dot center dot center dot H/H center dot center dot center dot C (23.4% for I; 26.3% for II) interactions are the most significant contributors to the crystal packing

Novel cyclic thiourea derivatives of aminoalcohols at the presence of AlCl3 catalyst as potent alpha-glycosidase and alpha-amylase inhibitors: Synthesis, characterization, bioactivity investigation and molecular docking studies

The article is devoted to the targeted synthesis and study of cyclic thiourea and their various new derivatives as new organic compounds containing polyfunctional group in the molecule. First time the reaction of the corresponding synthesized pyrimidinethione with 1,2-epoxy-3-chlorpropane at the presence of AlCl3 catalyst in 75-80 yield alkyl-1-(3-chloro-2-hydroxypropyl)-4-alkyl-6-phenyl-2-thioxo-1,2,5,6- tetrahydropyrimidine-5-carboxylates. In the next stage, new cyclic thiourea derivatives of aminoalcohols were synthesised from the reaction of chlorinated derivatives of pyrimidinethiones with single amines and their structures were investigated by spectroscopic methods. In this study, a series of novel compounds were tested towards some metabolic enzymes including alpha-glycosidase (alpha-Gly) and alpha-amylase (alpha-Amy) enzymes. Novel compounds showed Kis in ranging of 10.43 +/- 0.94-111.37 +/- 13.25 microM on alpha-glycosidase and IC50 values in ranging of 14.38-106.51 microM on alpha-amylase. The novel cyclic thiourea derivatives of aminoalcohols had effective inhibition profiles against all tested metabolic enzymes. Binding affinity and inhibition mechanism of the most active compounds were detected with in silico studies and have shown that 2-Hydroxypropyl and butan-1-aminium moieties play a key role for inhibition of the enzymes

Synthesis, characterization, antioxidant, antidiabetic, anticholinergic, and antiepileptic properties of novel N‐substituted tetrahydropyrimidines based on phenylthiourea

In the presence of trifluoroacetic acid, on the basis of three-component condensation of phenylthiourea with its salicylaldehyde and methyl-3-oxobutanoate, an efficient method for the synthesis of 1-(4-(2-hydroxyphenyl)-6-methyl-1-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)ethanone (I) has been worked out. These novel N-substituted tetrahydropyrimidines based on phenylthiourea showed good inhibitory action against acetylcholinesterase (AChE), alpha-glycosidase, and human carbonic anhydrase (hCA) isoforms I and II. K-i values of AChE enzyme were in the range of 0.48 to 7.46 nM. The hCA I and II were effectively inhibited by the compounds, with K-i values in the range of 502.44 to 923.11 nM for hCA I and 400.32 to 801.57 nM for hCA II, respectively. The antioxidant activity of the novel N-substituted tetrahydropyrimidines based on phenylthiourea was investigated by using different in vitro antioxidant assays; including 1,1-diphenyl-2-picrylhydrazyl (DPPH center dot) radical scavenging, Cu2+ and Fe3+ reducing activities

Crystal structure and Hirshfeld surface analysis of 2-(4-amino-6-phenyl-1,2,5,6-tetra­hydro-1,3,5-triazin-2-yl­­idene)malono­nitrile di­methyl­formamide hemisolvate

The title compound, 2C12H10N6·C3H7NO, crystallizes as a racemate in the monoclinic P21/c space group with two independent mol­ecules (I and II) and one di­methyl­formamide solvent mol­ecule in the asymmetric unit. Both mol­ecules (I and II) have chiral centers at the carbon atoms where the triazine rings of mol­ecules I and II are attached to the phenyl ring. In the crystal, mol­ecules I and II are linked by inter­molecular N—H⋯N, N—H⋯O and C—H⋯N hydrogen bonds through the solvent di­methyl­formamide mol­ecule into layers parallel to (001). In addition, C—H⋯π inter­actions also connect adjacent mol­ecules into layers parallel to (001). The stability of the mol­ecular packing is ensured by van der Waals inter­actions between the layers. The Hirshfeld surface analysis indicates that N⋯H/H⋯N (38.3% for I; 35.0% for II), H⋯H (28.2% for I; 27.0% for II) and C⋯H/H⋯C (23.4% for I; 26.3% for II) inter­actions are the most significant contributors to the crystal packing

Synthesis and discovery of potent carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase, and alpha-glycosidase enzymes inhibitors: The novel N,N '-bis-cyanomethylamine and alkoxymethylamine derivatives

During this investigation, N,N'-bis-azidomethylamines, N,N'-bis-cyanomethylamine, new alkoxymethylamine and chiral derivatives, which are considered to be a new generation of multifunctional compounds, were synthesized, functional properties were investigated, and anticholinergic and antidiabetic properties of those compounds were studied through the laboratory tests, and it was approved that they contain physiologically active compounds rather than analogues. Novel N-bis-cyanomethylamine and alkoxymethylamine derivatives were effective inhibitors of the alpha-glycosidase, cytosolic carbonic anhydrase I and II isoforms, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) with K-i values in the range of 0.15-13.31 nM for alpha-glycosidase, 2.77-15.30 nM for human carbonic anhydrase isoenzymes I (hCA I), 3.12-21.90 nM for human carbonic anhydrase isoenzymes II (hCA II), 23.33-73.23 nM for AChE, and 3.84-48.41 nM for BChE, respectively. Indeed, the inhibition of these metabolic enzymes has been considered as a promising factor for pharmacologic intervention in a diversity of disturbances