Ethyl 3-[7-(N-acetyl-4-meth-oxy-benzene-sulfonamido)-3-chloro-2H-indazol-2-yl]propionate.

In the title compound, C21H22ClN3O6S, the fused five- and six-membered ring rings are almost perpendicular to the planes through the atoms forming the acetyl and the propionic ester groups, as indicated by the dihedral angles of 80.3 (2) and 88.3 (7)°, respectively. The dihedral angle between the indazole system and the 4-meth-oxy-benzene-sulfonyl group is 13.76 (6)°. The carbonyl O atom is split over two positions in a 0.60 (5):0.40 (5) ratio. In the crystal, mol-ecules are linked by C-H⋯O and C-H⋯N inter-actions into a three-dimensional network.

1-(4-Methyl-phenyl-sulfon-yl)-5,6-di-nitro-1H-indazole.

In the title compound, C14H10N4O6S, the indazole ring system is almost perpendicular to the tosyl ring, as indicated by the dihedral angle of 89.40 (9)° between their planes. The dihedral angles between the indazole system and the nitro groups are 57.0 (3) and 31.9 (3)°. In the crystal, mol-ecules are linked by C-H⋯O inter-actions, forming chains running along [100].

Synthesis and antitumor activity of some substituted indazole derivatives.

Some new N-[6-indazolyl]arylsulfonamides and N-[alkoxy-6-indazolyl]arylsulfonamides were prepared by the reduction of 2-alkyl-6-nitroindazoles with SnCl2 in different alcohols, followed by coupling the corresponding amine with arylsulfonyl chlorides in pyridine. The newly synthesized compounds were evaluated for their antiproliferative and apoptotic activities against two human tumor cell lines: A2780 (ovarian carcinoma) and A549 (lung adenocarcinoma). Preliminary in vitro pharmacological studies revealed that N-(2-allyl-2H-indazol-6-yl)-4-methoxybenzenesulfonamide 4 and N-[7-ethoxy-2-(4-methyl-benzyl)-2H-indazol-6-yl]-4-methyl-benzenesulfonamide 9 exhibited significant antiproliferative activity against the A2780 and A549 cell lines with IC50 values in the range from 4.21 to 18.6 µM, and also that they trigger apoptosis in a dose-dependent manner. Furthermore, both active compounds were able to cause an arrest of cells in the G2/M phase of the cell cycle, typical but not exclusive of tubulin interacting agents, although only infrequent interactions with the microtubule network were observed by immunofluorescence microscopy, while docking analysis showed a possible different behavior between the two active compounds.

5,11-Ditosyl-5H,11H-dibenzo[b,f][1,5]diazo-cine-6,12-dione acetic acid hemisolvate.

The mol-ecular structure of the title compound, C28H22N2O6S2·0.5CH3COOH, is built up from three fused rings, two six and one eight membered. The eight-membered ring shows a boat conformation and the dihedral angle between the two benzene groups attached thereto is 66.43 (11)°, resulting in a V-shaped geometry. Two tosyl substituents are bound to the N atoms. The planes through the tolyl rings are roughly perpendicular, as indicated by the dihedral angle of 82.44 (12)°. In the crystal, the mol-ecule and its inversion-related symmetry-equivalent are linked to the acetic acid solvent mol-ecule by non-classical O-H⋯O and C-H⋯O hydrogen bonds. Two half-occupied acetic acid solvent mol-ecules are disordered at the same site and linked by a center of symmetry.

Ethyl 3-[6-(4-meth-oxy-benzene-sulfon-amido)-2H-indazol-2-yl]propano-ate monohydrate.

In the title compound, C(19)H(21)N(3)O(5)S·H(2)O, the central indazole system is essentially planar (r.m.s. deviation = 0.012 Å), while both the benzene ring and the mean plane defined by the non-H atoms of the ethyl propionic ester unit (r.m.s. deviation = 0.087 Å) are nearly perpendicular to the indazole plane, as indicated by the dihedral angles of 82.45 (8) and 75.62 (8)°, respectively. Consequently, the mol-ecule adopts a U-shaped geometry. In the crystal, the water mol-ecule, which is linked to the indazole system by a strong O-H⋯N hydrogen bond, is also involved in two additional N-H⋯O and O-H⋯O inter-actions, which link the organic mol-ecules into chains along the b-axis direction.

Synthesis, antiproliferative and apoptotic activities of N-(6(4)-indazolyl)-benzenesulfonamide derivatives as potential anticancer agents.

Recently, it has been reported that compounds bearing a sulfonamide moiety possess many types of biological activities, including anticancer activity. The present work reports the synthesis and antiproliferative evaluation of some N-(6(4)-indazolyl)benzenesulfonamides and 7-ethoxy-N-(6(4)-indazolyl)benzenesulfonamides. All compounds were evaluated for their in vitro antiproliferative activity against three tumor cell lines: A2780 (human ovarian carcinoma) A549 (human lung adenocarcinoma) and P388 (murine leukemia). The results indicated that sulfonamides 2c, 3c, 6d, 8, 13, 3b and 16 were endowed with a pharmacologically interesting antiproliferative activity with compounds 2c and 3c showing the lower IC(50) (from 0.50 ± 0.09 to 1.83 ± 0.52 µM and from 0.58 ± 0.17 to 5.83 ± 1.83 µM, respectively). Moreover, these indazoles were able to trigger apoptosis through the upregulation of the typical apoptosis markers p53 and bax. As regard to the hypothetic targets of these compounds, a preliminary docking analysis showed that all compounds seemed to interact with ß-tubulin, in particular compound 3b that showed the lower Ki. The cytofluorimetric analysis of the cell cycle phases indicates that all compounds, when administered at their IC(75), caused a block in the G2/M phase of the cell cycle with the generation of subpopulations of cells with a number of chromosome >4n. When the IC(50)s were applied we observed a prevalent block in the G0/G1 phase except for compounds 16 and 8 where a partial G2/M block was present with a concomitant decrease of cells in the G0/G1 and S phases of the cell cycle. Altogether these results suggest a possible, but not exclusive, interaction with microtubules.

Ethyl 3-[7-eth-oxy-6-(4-meth-oxy-benzene-sulfonamido)-2H-indazol-2-yl]propano-ate.

In the title compound, C(21)H(25)N(3)O(6)S, the dihedral angle between the meth-oxy-benzene and indazole rings is 74.96 (5)°. The crystal packing is stabilized by an N-H⋯O hydrogen bond into a two-dimensional network. In addition, C-H⋯π inter-actions and a π-π contact, with a centroid-centroid distance of 3.5333 (6) Å, are observed. The crystal packing is stabilized by N-H⋯O and C-H⋯O hydrogen bonds.

N-[7-Eth-oxy-2-(prop-2-en-1-yl)-2H-indazol-6-yl]-4-methyl-benzene-sulfonamide.

In the title compound, C(19)H(21)N(3)O(3)S, the C-SO(2)-NH-C torsion angle is 66.20 (9)°. The dihedral angle between the benzene ring and the essentially planar indazole ring system [r.m.s. deviation = 0.0361 (1) Å] is 72.97 (6)°. The S atom has a distorted tetra-hedral geometry [maximum deviation = O-S-O = 119.30 (6)°]. The crystal structure features inversion-related dimers linked by pairs of N-H⋯O hydrogen bonds. In addition, weak C-H⋯O inter-actions may stabilize the crystal packing.

N-(2-Formyl-phen-yl)-4-meth-oxy-N-(4-meth-oxy-phenyl-sulfon-yl)benzene-sulfonamide.

In the title compound, C(21)H(19)NO(7)S(2), the dihedral angles between the formyl-phenyl ring and the two meth-oxy-phenyl rings are 33.87 (9) and 41.00 (10)°. The S atoms have a distorted tetra-hedral geometry and the N atom shows a trigonally planar [r.m.s. deviation = 0.0437 (13) Å] coordination. The crystal structure is stabilized by inter-molecular C-H⋯O hydrogen bonds.

N-[7-Eth-oxy-1-(prop-2-en-1-yl)-1H-indazol-4-yl]-4-methyl-benzene-sulfonamide.

In the title compound, C(19)H(21)N(3)O(3)S, the C-SO(2)-NH-C torsion angle is 103.72 (11)°. The almost planar indazole ring [r.m.s. deviation = 0.0202 (14) Å] is twisted away from the methyl-benzene ring by 76.87 (7)°. The vinyl group is disordered over two orientations with site occupancies of 0.622 (10) and 0.378 (10). The S atom has a distorted tetra-hedral geometry [maximum deviation: O-S-O = 119.18 (11)°]. An intra-molecular C-H⋯O hydrogen bond occurs. In the crystal, two mol-ecules are linked about a center of inversion by pairs of N-H⋯O hydrogen bonds, generating a dimer. C-H⋯π inter-actions are also observed.

N-(7-Eth-oxy-1H-indazol-4-yl)-4-methyl-benzene-sulfonamide.

The mol-ecule of the title heterocyclic compound, C(16)H(17)N(3)O(3)S, is bent at the S atom with an C-SO(2)-NH-C torsion angle of 80.17 (8)°. The phenyl substituent at the S atom is rotated out of the plane of the 1H-indazole ring [inter-planar angle = 46.24 (8)°]. In the crystal, inter-molecular N-H⋯N and N-H⋯O hydrogen bonds build up a ribbon developing parallel to the b-axis direction. C-H⋯O hydrogen bonds link these ribbons, forming a layer parallel to the bc plane.