Crystal structures of four thio-glycosides involving carbamimido-thio-ate groups.

The compounds 2',3',4',6'-tetra-O-acetyl-ß-d-gluco-pyranosyl N'-cyano-N-phenyl-carbamimido-thio-ate (C22H25N3O9S, 5a), 2',3',4',6'-tetra-O-acetyl-ß-d-galacto-pyranosyl N'-cyano-N-phenyl-carbamimido-thio-ate, (C22H25N3O9S, 5b), 2',3',4',6'-tetra-O-acetyl-ß-d-galacto-pyranosyl N'-cyano-N-methyl-carbamimido-thio-ate (C17H23N3O9S, 5c), and 2',3',4',6'-tetra-O-acetyl-ß-d-galacto-pyranosyl N'-cyano-N-p-tolyl-carbamimido-thio-ate (C23H27N3O9S, 5d) all crystallize in P212121 with Z = 4. For all four structures, the configuration across the central (formal) C=N(CN) double bond of the carbamimido-thio-ate group is Z. The torsion angles C5-O1-C1-S (standard sugar numbering) are all close to 180°, confirming the ß position of the substituent. Compound 5b involves an intra-molecular hydrogen bond N-H⋯O1; in 5c this contact is the weaker branch of a three-centre inter-action, whereas in 5a and 5d the H⋯O distances are much longer and do not represent significant inter-actions. The C-N bond lengths at the central carbon atom of the carbamimido-thio-ate group are almost equal. All C-O-C=O torsion angles of the acetyl groups correspond to a synperiplanar geometry, but otherwise all four mol-ecules display a high degree of conformational flexibility, with many widely differing torsion angles for equivalent groups. In the crystal packing, 5a, 5c and 5d form layer structures involving the classical hydrogen bond N-H⋯Ncyano and a variety of 'weak' hydrogen bonds C-H⋯O or C-H⋯S. The packing of 5b is almost featureless and involves a large number of borderline 'weak' hydrogen bonds. In an appendix, a potted history of wavelength preferences for structure determination is presented and it is recommended that, even for small organic crystals in non-centrosymmetric space groups, the use of Mo radiation should be considered.

Novel synthesis of the first new class of triazine sulfonamide thioglycosides and the evaluation of their anti-tumor and anti-viral activities against human coronavirus.

Novel class of triazine sulfonamide thioglycosides was designed and synthesized. Those novel structures comprising three essential and pharmacological significant moieties such as the triazine, sulfonamide, and thioglycosidic scaffolds. The triazine sulfonamides were furnished via a direct approach starting from potassium cyanocarbonimidodithioate, then the corresponding triazine sulfonamide thioglycosides were generated using the peracylated α-d-gluco- and galacto-pyranosyl bromides. Anti-viral evaluation of compounds in vitro against HCoV-229E virus revealed that some compounds possess promising activity. Compounds 4a, 4b, 4d, 6d and 6e indicate from moderate to low antiviral activity against low pathogenic coronavirus 229E in comparison with remdesivir at a concentration of 100 µg/mL. Additionally their in vitro anti-proliferative effects against NCI 60 cancer cell lines cell lines were also investigated. Compound 4a, the most potent compound among the estimated compounds, revealed remarkably lowest cell growth promotion against CNS cancer SNB-75, and renal cancer UO-31.

Design and synthesis of novel 1,3,4-thiadiazole thioglycosides as promising antimicrobial potent structures.

Thiosemicarbazide was used as a key starting material for the building of a diversity of novel heterocyclic moieties. The heterocyclization reaction of thiosemicarbazide derivatives with carbon disulfide in basic conditions afforded novel heterocyclic 1,3,4-thiadiazolethiolate derivatives. 1,3,4-thiadiazole-2-thiol was successfully reacted with protected α-D-gluco- and galacto-pyranosyl bromides in dimethylformamide at room temperature to give the matching 1,3,4-thiadiazole S-glycosides in good yields. The latter compounds were reacted with ammonia-methanol at room temperature for 10 min, and the deprotected derivatives were obtained in good yields. The newly synthesized compounds were characterized by basic analyses and spectral information (IR,1H NMR, and 13C NMR, X-ray). All newly produced compounds were evaluated and screened for their antibacterial activities. Compound 6f proved to be the most active antimicrobial among the investigated heterocycles.

Crystal structure of (E)-N-(4-bromo-phen-yl)-2-cyano-3-[3-(2-methyl-prop-yl)-1-phenyl-1H-pyrazol-4-yl]prop-2-enamide.

The structure of the title compound, C23H21BrN4O, contains two independent mol-ecules connected by hydrogen bonds of the type Namide-H⋯N≡C to form a dimer. The configuration at the exocyclic C=C double bond is E. The mol-ecules are roughly planar except for the isopropyl groups. There are minor differences in the orientations of these groups and the phenyl rings at N1. The dimers are further linked by 'weak' hydrogen bonds, two each of the types Hphen-yl⋯O=C (H⋯O = 2.50, 2.51 Å) and Hphen-yl⋯Br (H⋯Br = 2.89, 2.91 Å), to form ribbons parallel to the b and c axes, respectively. The studied crystal was a non-merohedral twin.

Crystal structure of 2,4-di-amino-5-(4-hy-droxy-3-meth-oxy-phen-yl)-8,8-dimethyl-6-oxo-6,7,8,9-tetra-hydro-5H-chromeno[2,3-b]pyridine-3-carbo-nitrile-di-methyl-formamide-water (1/1/1).

In the structure of the title compound, C22H22N4O4·C3H7NO·H2O, the entire tricyclic system is approximately planar except for the carbon atom bearing the two methyl groups; the meth-oxy-phenyl ring is approximately perpendicular to the tricycle. All seven potential hydrogen-bond donors take part in classical hydrogen bonds. The main mol-ecule and the DMF combine to form broad ribbons parallel to the a axis and roughly parallel to the ab plane; the water mol-ecules connect the residues in the third dimension.

Synthesis and crystal structure of N-phenyl-2-(phenyl-sulfan-yl)acetamide.

N-Phenyl-2-(phenyl-sulfan-yl)acetamide, C14H13NOS, was synthesized and structurally characterized. In the crystal, N-H⋯O hydrogen bonding leads to the formation of chains of mol-ecules along the [100] direction. The chains are linked by C-H⋯π inter-actions, forming a three-dimensional network. The crystal studied was twinned by a twofold rotation around [100].

Crystal structure of 4-(benzo[d]thia-zol-2-yl)-1,2-dimethyl-1H-pyrazol-3(2H)-one.

In the title compound, C12H11N3OS, the inter-planar angle between the pyrazole and benzo-thia-zole rings is 3.31 (7)°. In the three-dimensional mol-ecular packing, the carbonyl oxygen acts as acceptor to four C-H donors (with one H⋯O as short as 2.25 Å), while one methyl hydrogen is part of the three-centre system H⋯(S, O). A double layer structure parallel to (01) can be recognized as a subsection of the packing.

Novel synthesis of new triazine sulfonamides with antitumor, anti-microbial and anti-SARS-CoV-2 activities.

Novel approach for synthesizing triazine sulfonamide derivatives is accomplished via reacting the sulfaguanidine derivatives with N-cyanodithioiminocarbonate. Further reaction of the novel triazine sulfonamide analogues with various secondary amines and anilines generated various substituted triazine sulfonamide analogues of promising broad-spectrum activities including anti-microbial, anti-tumor, and anti-viral properties. The in vitro anti-proliferative activities of most of the novel compounds were evaluated on the NCI-60 cell line panel. The antifungal and antibacterial activities of the compounds were also estimated. The anti-viral activity against SARS CoV-2 virus was performed using MTT cytotoxicity assay to evaluate the half-maximal cytotoxic concentration (CC50) and inhibitory concentration 50 (IC50) of a representative compound from the novel triazine sulfonamide category. Compound 3a demonstrated potent antiviral activity against SARS-CoV-2 with IC50 = 2.378 µM as compared to the activity of the antiviral drug remdesivir (IC50 = 10.11 µM). Our results indicate that, upon optimization, these new triazine sulfonamides could potentially serve as novel antiviral drugs.

Crystal structure of 2-[(5-amino-1-tosyl-1H-pyrazol-3-yl)-oxy]-1-(4-meth-oxy-phen-yl)ethan-1-one 1,4-dioxane monosolvate.

In the structure of the title compound, C19H19N3O5S·C4H8O2, the two independent dioxane mol-ecules each display inversion symmetry. The pyrazole ring is approximately parallel to the aromatic ring of the oxy-ethanone group and approximately perpendicular to the tolyl ring of the sulfonyl substituent. An extensive system of classical and 'weak' hydrogen bonds connects the residues to form a layer structure parallel to (201), within which dimeric subunits are conspicuous; neighbouring layers are connected by classical hydrogen bonds to dioxanes and by 'weak' hydrogen bonds from Htol-yl donors.

An unexpected tautomer: synthesis and crystal structure of N-[6-amino-4-(methyl-sulfan-yl)-1,2-di-hydro-1,3,5-triazin-2-yl-idene]benzenesulfonamide.

The title compound, C10H11N5O2S2, consists of an unexpected tautomer with a protonated nitro-gen atom in the triazine ring and a formal exocyclic double bond C=N to the sulfonamide moiety. The ring angles at the unsubstituted nitro-gen atoms are narrow, at 115.57 (12) and 115.19 (12)°, respectively, whereas the angle at the carbon atom between these N atoms is very wide, 127.97 (13)°. The inter-planar angle between the two rings is 79.56 (5)°. The mol-ecules are linked by three classical hydrogen bonds, forming a ribbon structure. There are also unusual linkages involving three short contacts (< 3 Å) from a sulfonamide oxygen atom to the C-NH-C part of a triazine ring.