Synthesis and antidiabetic activity of 2,4-thiazolidindione, imidazolidinedione and 2-thioxo-imidazolidine-4-one derivatives bearing 6-methyl chromonyl pharmacophore.

Numerous compounds have been prepared in order to improve the pharmacological profile of insulinotropic activities. In the present paper, we report the synthesis and the in vitro insulin releasing activity of the 6-methyl-chromonyl-2,4-thiazolidinediones (IIIa-c, IVa-c, Va-c). Compounds IIIb, IIIc, IVa-c, Va and Vc (at lower concentration; 0.001 mg/mL) were able to increase insulin release in the presence of 5.6 mmol/L glucose. In this series, the most potent compound is IVa having methyl group at N3 position of TZD ring.

2-(4-Bromo-phen-yl)-4-(4-meth-oxy-phen-yl)-6,7,8,9-tetra-hydro-5H-cyclo-hepta-[b]pyridine.

In the title compound, C23H22BrNO, the cyclo-heptane ring adopts a chair conformation. The pyridine ring makes dihedral angles of 58.63 (15) and 8.27 (16)° with the benzene rings. The dihedral angle between the benzene rings is 56.68 (17)°. The crystal packing features C-Br⋯π inter-actions [Br⋯centroid distances= 3.813 (2) and 3.839 (2) Å; C-Br⋯centroid = 126.25 (10) and 138.31 (10)°, respectively, forming a three dimensional supramolecular architecture.

Design and one-pot and microwave-assisted synthesis of 2-amino/5-aryl-1,3,4-oxadiazoles bearing a benzimidazole moiety as antioxidants.

In this study, two new series of 2-amino-1,3,4-oxadiazoles and 5-aryl-1,3,4-oxadiazoles carrying a benzimidazole moiety were synthesized. The antioxidant properties of these compounds were investigated in vitro by the determination of the microsomal NADPH-dependent inhibition of lipid peroxidation levels (LP), the microsomal ethoxyresorufin O-deethylase activity (EROD), and DPPH radical scavenger effects. Among the tested compounds, 2-[(2-(4-chlorophenyl)-1H-benzo[d]imidazole-1-yl)methyl]-5-(4-fluorophenyl)-1,3,4-oxadiazole (9) was found to be the most active compound in all three in vitro systems.

5-Diethyl-amino-2-{(E)-[(3-iodo-phen-yl)imino]-meth-yl}phenol.

The title Schiff base, C(17)H(19)IN(2)O, is not planar, displaying a dihedral angle of 34.9 (2)° between the two aromatic rings. The mol-ecular conformation allows the formation of a strong intra-molecular O-H⋯N hydrogen bond with graph-set motif S(6) between the hy-droxy group and the imine N atom.

2-(2-Fluoro-4-hy-droxy-benz-yl)isoindoline-1,3-dione.

In the title compound, C(15)H(10)FNO(3), the dihedral angle between the isoindoline-1,3-dione and 3-fluoro-4-methyl-phenol groups is 86.88 (8)°. The isoindoline-1,3-dione fragment is almost planar, with an r.m.s. deviation of 0.0154 Šwithin the group. Inter-molecular C-H⋯O hydrogen bonds generate C(6) chains running parallel to the [010] direction.

(E)-N-[(2-Eth-oxy-naphthalen-1-yl)methyl-idene]-2-ethyl-aniline.

In the title compound, C(21)H(21)NO, the dihedral angle between the naphthalene ring system and the benzene ring is 64.61 (6)°. The mol-ecular structure is stabilized by an intra-molecular C-H⋯N hydrogen bond.

(E)-4-Hy-droxy-N'-(2-hy-droxy-5-iodo-benzyl-idene)benzohydrazide methanol monosolvate.

In the title compound, C(14)H(11)IN(2)O(3)·CH(4)O, the dihedral angle between the benzene rings is 33.2 (3)°. The mol-ecule displays trans and anti conformations about the C=N and N-N bonds, respectively. There is an intra-molecular O-H⋯N(azomethine) hydrogen bond. Inter-molecular N-H⋯O and O-H⋯O hydrogen bonds consolidate mol-ecules into a three-dimensional architecture.

(E)-3-Chloro-N-[(2-eth-oxy-naphthalen-1-yl)methyl-idene]aniline.

In the title compound, C(19)H(16)ClNO, the dihedral angle between the naphthalene ring system and the chloro-benzene ring is 61.90 (10)° and the C-N-C-C torsion angle is 174.6 (2)°. The mol-ecular structure is stabilized by an intra-molecular C-H⋯N hydrogen bond. The crystal structure features π-π stacking inter-actions [centroid-centroid distances = 3.7325 (17) and 3.8150 (17) Å].

2,4-Dibromo-2,3-dihydro-1H-inden-1-yl acetate.

In the title compound, C(11)H(10)Br(2)O(2), the cyclo-pentene ring fused to the benzene ring adopts an envelope conformation, with the C atom attached to the Br atom as the flap. The crystal structure does not exhibit any classical hydrogen bonds. The mol-ecular packing is stabilized by van der Waals forces and π-π stacking inter-actions with a centroid-centroid distance of 3.811 (4) Å.

(E,E)-N'-{4-[(2-Benzoyl-hydrazin-1-yl-idene)meth-yl]benzyl-idene}benzo-hydrazide.

In the title compound, C(22)H(18)N(4)O(2), the mol-ecules lie across an inversion centre. The dihedral angle between the mean planes of the central and terminal benzene rings is 66.03 (2)°. The mol-ecule displays trans and anti conformations about the C=N and N-N bonds, respectively. In the crystal, N-H⋯O hydrogen bonds, with the O atoms of C=O groups acting as acceptors, link the mol-ecules into a chain along [101].

(E)-1-{2-Hy-droxy-5-[(4-methyl-phen-yl)diazen-yl]phen-yl}ethanone.

The structure of the title compound, C(15)H(14)N(2)O(2), an azo dye, displays a trans configuration with respect to the N=N bridge. The dihedral angle between the aromatic rings is 5.06 (8)°. The mol-ecular conformation is stabilized by a strong intra-molecular O-H⋯O hydrogen bond. In the crystal, inter-molecular C-H⋯O hydrogen bonds occur.

3-Amino-4-[4-(dimethyl-amino)-phen-yl]-4,5-dihydro-1,2,5-thia-diazole 1,1-dioxide.

The title compound, C(10)H(14)N(4)O(2)S, exists in the amine tautomeric form. The dihedral angle between the benzene and thia-diazo-lidine rings is 66.54 (19)°. In the crystal, mol-ecules are linked by N-H⋯O and N-H⋯N hydrogen bonds into a layer parallel to the ac plane. The layers are further linked by C-H⋯O hydrogen bonds.

(E)-N'-(2-Hy-droxy-benzyl-idene)furan-2-carbohydrazide.

In the title compound, C(12)H(10)N(2)O(3), the dihedral angle between the benzene ring and the furan ring is 16.12 (13)°. The conformation is stabilized by an intra-molecular O-H⋯N hydrogen bond. Inter-molecular N-H⋯O hydrogen bonds with the keto group as acceptor lead to strands along [001]. The mol-ecule displays a trans configuration with respect to the C=N and N-N bonds.

(2Z,N'E)-N'-[(2-Hy-droxy-1-naphth-yl)methyl-idene]furan-2-carbohydrazonic acid.

In the title compound, C(16)H(12)N(2)O(3), the dihedral angle between the mean planes of the naphthalene ring system and the furan ring is 21.3 (6)°. The mol-ecular structure is stabilized by an intra-molecular O-H⋯N hydrogen bond, which generates an S(6) graph-set motif.

Structural characterization and EPR spectral studies on mononuclear copper(II) complex of saccharin with ethylnicotinate.

Mononuclear copper(II) saccharinate (sac) complex containing ethylnicotinate (enc), [Cu(enc)(2)(sac)(2)(H(2)O)].1.4H(2)O has been synthesized and characterized by spectroscopic (IR, UV-vis, EPR), X-ray diffraction technique and electrochemical methods. It crystallizes in the tetragonal crystal systems with space group I4(1)cd and Z=8. The copper(II) ion presents a CuN(4)O distorted square pyramidal coordination. Based on EPR and optical absorption studies, spin-Hamiltonian and bonding parameters have been calculated. The g-values, calculated for title complex in polycrystalline state at 298 K and in frozen DMF (110K), indicate the presence of the unpaired electron in the d(x)(2)-(y)(2) orbital. The evaluated metal-ligand bonding parameters showed strong in-plane sigma and in-plane pi-bonding. Some comparisons with related structures are made and the most important features of its IR spectrum were also discussed. The cyclic voltammogram of the title complex investigated in DMF (dimethylformamide) solution exhibits only metal centred electroactivity in the potential range +/-1.25 V vs. Ag/AgCl reference electrode.

Diaqua-bis(ethyl-enediamine-κN,N')copper(II) 2,2'-dithio-dinicotinate sesquihydrate.

In the title compound, [Cu(C(2)H(8)N(2))(2)](C(12)H(6)N(2)O(4)S(2))·1.5H(2)O, there are two half-molecules of the cationic complex in the asymmetric unit. The Cu(2+) ions lie on inversion centres and are octa-hedrally coordinated by two ethyl-enediamine (en) and two aqua ligands in a typical Jahn-Teller distorted environment with the water O atoms in the axial positions. Two 2-mercaptonicotinate units (mnic) are linked by a disulfide bridge. All the ethyl-enediamine N-H and O-H groups form inter-molecular hydrogen bonds with acceptor O and N atoms, giving rise to a three-dimensional network. One of the uncoordinated water molecules has a site occupation factor of 0.5.

Methyl 1H-1,2,3-triazole-4-carboxyl-ate.

The title compound, C(4)H(5)N(3)O(2), features an essentially planar mol-ecule (r.m.s. deviation for all non-H atoms = 0.013 Å). The crystal structure is stabilized by inter-molecular N-H⋯O hydrogen bonds and π-π stacking inter-actions (centroid-centroid distance 3.882 Å).

1,3-Dimethyl-2,6-diphenyl-piperidin-4-one.

In the title moleclue, C(19)H(21)NO, the 4-piperidone ring adopts a chair conformation in which the two benzene rings and the methyl group attached to C atoms all have equatorial orientations. In the crystal structure, centrosymmetric dimers are formed through weak inter-molecular C-H⋯O hydrogen bonds [the dihedral angle between the aromatic rings is 58.51 (5)°].

trans-Bis[2-(piperazin-1-yl)-ethan-amine]-bis-(saccharinato)cobalt(II).

In the centrosymmetric title complex, [Co(C(7)H(4)NO(3)S)(2)(C(6)H(15)N(3))(2)], the Co(II) ion is coordinated by two saccharinate (sac) anions and two neutral 2-piperazin-1-ylethanamine (ppzea) ligands, showing a distorted octa-hedral coordination. Sac is O-bonded via the carbonyl group, while ppzea acts as an N,N'-bidentate chelating ligand. The mol-ecules are connected by N-H⋯N and N-H⋯O hydrogen bonds, forming a linear chain running parallel to the crystallographic a axis. The compound is isostructural with the reported Ni, Zn, and Cd analogues.

Synthesis of novel substituted purine derivatives and identification of the cell death mechanism.

Novel 9-(substituted amino/piperazinoethyl)adenines (4-12), 6-(substituted piperazino/amino)purines (15-27), 9-(p-toluenesulfonyl/cyclopentyl/ethoxycarbonylmethyl)-6-(substituted amino/piperazino)purines (28-34, 36, 37, 38-41) were synthesized and evaluated initially for their cytotoxic activities on liver Huh7, breast T47D and colon HCT116 carcinoma cells. N(6)-(4-Trifluoromethylphenyl)piperazine derivative (17) and its 9-(p-toluene-sulfonyl)/9-cyclopentyl analogues (28, 36) had promising cytotoxic activities. Compounds 17, 28 and 36 were further analysed for their cytotoxicity in a panel of a liver cancer cell lines. The compound 36 had better cytotoxic activities (IC50 ≤ 1 µM) than the nucleobase 5-FU and nucleosides fludarabine, cladribine, and pentostatine on Huh7 cells. Cytotoxicity induced by 36 was later identified as senescence associated cell death by SA-ß-Gal assay.