Synthesis, characterization, and inhibition effects of a novel eugenol derivative bearing pyrrole functionalities on the corrosion of mild steel in a HCl acid solution.

Semi-synthetic modifications of natural products have yielded numerous anti-cancer drugs, antimicrobials, and corrosion inhibitors. In this study, eugenol, a natural product, was synthetically modified to generate a novel heterocyclic compound: pyrrole, which forms crystals. The latter is the outcome of the condensation reaction between eugenol hydrazide and 2,5-hexanedione, conducted under reflux ethanol conditions, without a catalyst, achieving a 96% yield. This compound structure was characterized through spectroscopic methods, such as NMR and FTIR, and validated par the crystal's X-ray diffraction analysis. According to the findings of the electrochemical study, pyrrole demonstrated effective inhibition against the carbon steel's corrosion in a 1 M HCl acid solution.

Synthesis, crystal structure and Hirshfeld surface analysis of dimethyl 3-(3-bromo-phen-yl)-6-methyl-7-oxo-3,5,6,7-tetra-hydro-pyrazolo-[1,2-a]pyrazole-1,2-di-carboxyl-ate.

The title compound, C17H17BrN2O5, resulted from the 1,3-dipolar cyclo-addition reaction between dimethyl acetyl-enedi-carboxyl-ate and (3-bromo-benzyl-idene)-4-methyl-5-oxopyrazolidin-2-ium-1-ide in CHCl3. The dihedral angle between the pyrazole rings (all atoms) is 32.91 (10)°; the oxo-pyrazole ring displays an envelope conformation whereas the other pyrazole ring adopts a twisted conformation. The bromo-phenyl ring subtends a dihedral angle of 88.95 (9)° with the mean plane of its attached pyrazole ring. In the crystal, the mol-ecules are linked by C-H⋯O hydrogen bonds and aromatic π-π inter-actions with an inter-centroid distance of 3.8369 (10) Å. The Hirshfeld surface analysis and fingerprint plots reveal that the mol-ecular packing is governed by H⋯H (37.1%), O⋯H/H⋯O (31.3%), Br⋯H/H⋯Br (13.5%) and C⋯H/H⋯C (10.6%) contacts. The energy framework indicates that dispersion energy is the major contributor to the mol-ecular packing.

Antiproliferative and apoptotic activity of new indazole derivatives as potential anticancer agents.

To develop potent and selective anticancer agents, a series of novel polysubstituted indazoles was synthesized and evaluated for their in vitro antiproliferative and apoptotic activities against two selected human cancer cell lines (A2780 and A549). Several compounds showed an interesting antiproliferative activity, with IC50 values ranging from 0.64 to 17 µM against both cell lines. The most active indazoles were then tested in different pharmacological dilution conditions, adding five new cell lines (A2780, A549, IMR32, MDA-MB-231, and T47D) as targets, confirming their antiproliferative activity. Furthermore, selected compounds were able to trigger apoptosis to a significant extent and to cause, in part, a block of cells in the S phase of the cell cycle, with a concomitant decrease of cells in the G2/M and/or G0/G1 phases and the generation of hypodiploid peaks. However, molecule 7d caused a great increase of cells in G2/M and the appearance of polyploid cells. Altogether, our results suggest a good pharmacological activity for our selected polysubstituted indazoles, which are suggestive of a preferential mechanism of action as cell cycle-specific antimetabolites or as an inhibitor of enzyme activities involved in DNA synthesis, except for 7d, which, on the contrary, seems to have a mechanism involving the microtubule system.

Ethyl 10α-hy-droxy-4,9-dimethyl-14-oxo-3,8,15-trioxa-tetra-cyclo-[10.3.0.02,4.07,9]penta-decane-13-spiro-5'-pyrazole-3'-carboxyl-ate.

The ten-membered ring in the title mol-ecule, C25H29ClN2O7, adopts an approximate chair-chair conformation, whereas the five-membered furan and pyrazole rings display envelope conformations. The mean plane of the furan ring is almost perpendicular to that of the pyrazole ring, as indicated by the dihedral angle between them of 86.45 (9)°. The pyrazole ring is slightly inclined to the plane of the attached phenyl ring, subtending a dihedral angle of 16.88 (8)°. The conformation of the mol-ecule is stabilized by six intra-molecular hydrogen bonds and crystal cohesion is ensured by five C-H⋯O hydrogen bonds, in addition to C-H⋯π inter-actions.

A Suitable Functionalization of Nitroindazoles with Triazolyl and Pyrazolyl Moieties via Cycloaddition Reactions.

The alkylation of a series of nitroindazole derivatives with 1,2-dibromoethane afforded the corresponding N-(2-bromoethyl)- and N-vinyl-nitro-1H-indazoles. The Cu(I)-catalysed azide- alkyne 1,3-dipolar cycloaddition was selected to substitute the nitroindazole core with 1,4-disubstituted triazole units after converting one of the N-(2-bromoethyl)nitroindazoles into the corresponding azide. The reactivity in 1,3-dipolar cycloaddition reactions with nitrile imines generated in situ from ethyl hydrazono-α-bromoglyoxylates was studied with nitroindazoles bearing a vinyl unit. The corresponding nitroindazole-pyrazoline derivatives were obtained in good to excellent yields.

Crystal structure of 3-chloro-1-methyl-5-nitro-1H-indazole.

The mol-ecule of the title compound, C8H6ClN3O2, is built up from fused five- and six-membered rings connected to a chlorine atom and to nitro and methyl groups. The indazole system is essentially planar with the largest deviation from the mean plane being 0.007 (2) Å. No classical hydrogen bonds are observed in the structure. Two mol-ecules form a dimer organised by a symmetry centre via a close contact between a nitro-O atom and the chlorine atom [at 3.066 (2) Šthis is shorter than the sum of their van der Waals radii].

Crystal structure of (E)-3-allyl-2-sulfanyl-idene-5-[(thio-phen-2-yl)methyl-idene]thia-zolidin-4-one.

Mol-ecules of the title compound, C11H9NOS3, are built up by one thio-phene and one 2-thioxa-thia-zolidin-4-one ring which are connected by a methyl-ene bridge. In addition, there is an allyl substituent attached to nitro-gen. The two rings are almost coplanar, making a dihedral angle between them of 0.76 (11)°. The allyl group is oriented perpendicular to the mean plane through both ring systems. The crystal structure exhibits inversion dimers in which mol-ecules are linked by pairs of C-H⋯O hydrogen bonds. Additional π-π inter-actions between neighboring thio-phene and 2-thioxa-thia-zolidin-4-one rings [inter-centroid distance = 3.694 (2) Å] lead to the formation of a three-dimensional network.

Crystal structure of (Z)-3-allyl-5-(3-bromo-benzyl-idene)-2-sulfanyl-idene-1,3-thia-zolidin-4-one.

In the title compound, C13H10BrNOS2, the rhodanine (systematic name: 2-sulfanyl-idene-1,3-thia-zolidin-4-one) and the 3-bromo-benzyl-idene ring systems are inclined slightly, forming a dihedral angle of 5.86 (12)°. The rhodanine moiety is linked to an allyl group at the N atom and to the 3-bromo-benzyl-idene ring system. The allyl group, C=C-C, is nearly perpendicular to the mean plane through the rhodanine ring, maling a dihedral angle of 87.2 (5)°. In the crystal, mol-ecules are linked by pairs of C-H⋯O hydrogen bonds, forming inversion dimers with an R 2 (2)(10) ring motif.

Crystal structure of (Z)-3-allyl-5-(4-chloro-benzyl-idene)-2-sulfanyl-idene-1,3-thia-zolidin-4-one.

In the title compound, C13H10ClNOS2, the dihedral angle between the rhodanine (r.m.s. deviation = 0.008 Å) and 4-chloro-benzyl-idene rings is 1.79 (11)°. The allyl group attached to the N atom, which lies almost perpendicular to the rhodanine ring, is disordered over two orientations in a 0.519 (13):0.481 (13) ratio. A short intra-molecular C-H⋯S inter-action closes an S(6) ring. In the crystal, mol-ecules are linked by π-π stacking inter-actions [centroid-centroid separation = 3.600 (15) Å], generating inversion dimers.

Crystal structure of (Z)-3-allyl-5-(4-methyl-benzyl-idene)-2-sulfanyl-idene-1,3-thia-zolidin-4-one.

In the title compound, C14H13NOS2, the atoms of the allyl group are disordered over two sets of sites, with an occupancy ratio of 0.559 (10):0.441 (10). The rhodanine ring makes a dihedral angle of 5.51 (12)° with the mean plane through the p-tolyl group. There are no specific inter-molecular inter-actions in the crystal packing.

Crystal structure of N-(1-acetyl-3-chloro-1H-indazol-6-yl)-4-meth-oxy-benzene-sulfonamide.

In the title compound, C16H14ClN3O4S, the six-membered ring of the indazole group is connected to a sulfonamide group. The indazole system is essentially planar, with the greatest deviation from the mean plane being 0.007 (2) Å. The dihedral angle between the two six-membered rings is 74.99 (9)°. The crystal structure exhibits inversion dimers in which mol-ecules are linked by pairs of N-H⋯O and C-H⋯O hydrogen bonds.

Crystal structure of N-(1-allyl-3-chloro-4-eth-oxy-1H-indazol-5-yl)-4-meth-oxybenzene-sulfonamide.

In the title compound, C19H20ClN3O4S, the benzene ring is inclined to the indazole ring system (r.m.s. deviation = 0.014 Å) by 65.07 (8)°. The allyl and eth-oxy groups are almost normal to the indazole ring, as indicated by the respective torsion angles [N-N-C-C = 111.6 (2) and C-C-O-C = -88.1 (2)°]. In the crystal, mol-ecules are connected by N-H⋯N hydrogen bonds, forming helical chains propagating along [010]. The chains are linked by C-H⋯O hydrogen bonds, forming a three-dimensional network.

Crystal structure of N-(1-allyl-3-chloro-1H-indazol-5-yl)-4-methyl-benzene-sulfonamide.

The 3-chloro-1H-indazole system in the title mol-ecule, C17H16ClN3O2S, is almost planar, with the largest deviation from the mean plane being 0.029 (2) Šfor one of the N atoms. This system is nearly perpendicular to the allyl chain, as indicated by the C-C-N-N torsion angle of -90.1 (6)° between them. The allyl group is split into two fragments, the major component has a site occupancy of 0.579 (7). The indazole system makes a dihedral angle of 47.53 (10)° with the plane through the benzene ring. In the crystal, mol-ecules are connected by N-H⋯O and C-H⋯O hydrogen bonds, forming a three-dimensional network.

Crystal structure of N-(3-chloro-1-methyl-1H-indazol-5-yl)-4-meth-oxy-benzene-sulfonamide.

In the title compound, C15H14ClN3O3S, the dihedral angle between the planes of the indazole ring system (r.m.s. deviation = 0.007 Å) and the benzene ring is 89.05 (7)°. The meth-oxy C atom deviates from its attached ring by 0.196 (3) Å. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R 2 (2)(8) loops. The dimers are connected into [010] chains by C-H⋯O inter-actions.

N-(1-Allyl-3-chloro-4-eth-oxy-1H-indazol-5-yl)-4-methyl-benzene-sulfonamide.

In the title compound, C19H20ClN3O3S, the benzene ring is inclined to the indazole ring system by 51.23 (8)°. In the crystal, mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming inversion dimers which stack in columns parallel to [011]. The atoms in the allyl group are disordered over two sets of sites with an occupancy ratio of 0.624 (8):0.376 (8).

N-(3-Chloro-4-eth-oxy-1-methyl-1H-indazol-5-yl)-4-meth-oxy-benzene-sulfonamide.

The indazole ring system of the title compound, C17H18ClN3O4S, is almost planar (r.m.s. deviation = 0.0113 Å) and forms dihedral angles of 32.22 (8) and 57.5 (3)° with the benzene ring and the mean plane through the 4-eth-oxy group, respectively. In the crystal, mol-ecules are connected by pairs of N-H⋯O hydrogen bonds into inversion dimers, which are further linked by π-π inter-actions between the diazole rings [inter-centroid distance = 3.4946 (11) Å], forming chains parallel to [101].

N-(2-Allyl-4-eth-oxy-2H-indazol-5-yl)-4-methyl-benzene-sulfonamide.

The indazole ring system of the title compound, C19H21N3O3S, is almost planar (r.m.s. deviation = 0.0192 Å) and forms dihedral angles of 77.99 (15) and 83.9 (3)° with the benzene ring and allyl group, respectively. In the crystal, centrosymmetrically related mol-ecules are connected by pairs of N-H⋯O hydrogen bonds into dimers, which are further linked by C-H⋯O hydrogen bonds, forming columns parallel to the b axis.

6,6'-Di-nitro-1,1'-(ethane-1,2-di-yl)di(1H-indazole).

The mol-ecule of the title compound, C16H12N6O4, is built up from two fused five- and six-membered rings linked by an ethyl-ene group. The dihedral angle between the planes through the indazole ring systems is 39.74 (5)°. The nitro groups are tilted by 7.2 (2) and 8.5 (2)° with respect to planes of the fused-ring systems. In the crystal, mol-ecules are linked by C-H⋯N and C-H⋯O hydrogen bonds into chains running parallel to the c axis.

1-Methyl-2-methyl-sulfanyl-6-nitro-1H-benzimidazole.

The mol-ecule of the title compound, C9H9N3O2S, is built up from fused five- and six-membered rings connected to methyl-sulfanyl and nitro groups, respectively. The mean plane through the fused ring system is inclined slightly relative to the plane passing through the nitro group [dihedral angle = 3.6 (2)°]. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds and π-π inter-actions between imidazole rings [inter-centroid distance = 3.667 (3) Å], forming a three-dimensional network.

N-(3-Chloro-1-methyl-1H-indazol-5-yl)-4-methylbenzene-sulfonamide.

The asymmetric unit of the title compound, C15H14ClN3O2S, contains two independent mol-ecules showing different conformations: in one mol-ecule, the indazole ring system makes a dihedral angle of 51.5 (1)° with the benzene ring whereas in the other, the indazole unit is almost perpendicular to the benzene ring [dihedral angle 77.7 (1)°]. In the crystal, the mol-ecules are linked by N-H⋯N and N-H⋯O hydrogen bonds, forming a set of four mol-ecules linked in pairs about an inversion centre.