nan Nithinchandra

Type II diabetes-related enzyme inhibition and molecular modeling study of a novel series of pyrazolone derivatives

AbstractInhibitors of alpha-amylase are targets for the development of novel drugs for the treatment of diabetes and obesity. Alpha amylase is an enzyme which increases the bio availability of glucose in the blood. Hence, the inhibition effects of alpha amylase of 2-[1-(4-isobutylphenyl)ethyl]-5-methyl-4-[2-(aryl-substituted)hydrazinylidene]-2,4-dihydro-3H-pyrazol-3-one (4a–l) were investigated, among them compounds 4d, 4f, 4a, and 4g have displayed good inhibitory activity. The compounds with significant results were further evaluated for their molecular modeling study using in silico method. The new series of compounds were synthesized by solvent-free microwave irradiation method and were characterized by spectral and analytical data.

(4-Methyl­phen­yl)[1-(4-methyl­phen­yl)-3-(5-nitro-2-fur­yl)-1H-pyrazol-4-yl]methanone

In the title pyrazole compound, C22H17N3O4, an intramolecular C—H⋯O contact generates a seven-membered ring, producing an S(7) ring motif. The furan and pyrazole rings are essentially planar [maximum deviations = 0.004 (1) and 0.004 (2) Å, respectively] and are almost coplanar, making a dihedral angle of 3.75 (10)°. One of the methylphenyl groups is inclined to the pyrazole ring, as indicated by the dihedral angle of 48.41 (9)°. In the crystal structure, molecules are linked into chains along [10] by C—H⋯O contacts. The crystal structure is further stabilized by π–π interactions [centroid–centroid distance = 3.4437 (10) Å].

1-[5-Methyl-1-(4-nitro-phen-yl)-1H-1,2,3-triazol-4-yl]ethanone.

The asymmetric unit of the title compound, C11H10N4O3, contains two independent molecules in which the benzene rings make dihedral angles of 38.3 (2) and 87.1 (2)° with respect to the triazole rings. In the crystal, the molecules are linked by C—H⋯O hydrogen bonds, forming chains along [021]. Further, weak C—O⋯π [3.865 (5) Å, 83.8 (3)°] and N—O⋯π [3.275 (5) and 3.240 (6) Å, 141.8 (4) and 102.8 (3)°] interactions are observed.

4-Bromo­acetyl-3-phenyl­sydnone

In the title compound (systematic name: 4-bromoacetyl-1,2,3-oxadiazol-3-ylium-5-olate), C10H7BrN2O3, the 1,2,3-oxadiazole ring and bromoacetyl group are essentially planar [maximum deviation = 0.010 (4) and 0.013 (3) Å respectively] and form dihedral angles of 59.31 (19) and 67.96 (11)°, respectively, with the phenyl ring. The 1,2,3-oxadiazole ring is twisted slightly from the mean plane of the bromoacetyl group, forming a dihedral angle of 9.16 (24)°. In the crystal, molecules are linked by pairs of weak C—H⋯O hydrogen bonds into inversion dimers with R 2 2(12) ring motifs. The dimers are further connected by weak C—H⋯O hydrogen bonds into an infinite tape parallel to the b axis. In addition, π–π stacking interactions [centroid–centroid distance = 3.6569 (19) Å] and short intermolecular contacts [O⋯O = 2.827 (3) and C⋯C = 3.088 (5) Å] are observed.

4-[(3-Benzamido­methyl-6-phenyl-6,7-dihydro-5H-1,2,4-triazolo[3,4-b][1,3,4]thia­diazin-7-yl)carbon­yl]-3-phenyl-1,2,3-oxadiazol-3-ium-5-olate 0.06-hydrate

The asymmetric unit of the title compound, C27H21N7O4S·0.06H2O, contains four syndone molecules and a water molecule with a site occupancy of 0.25. In two of the syndone molecules, three atoms in a terminal phenyl ring are disordered over two sets of sites, with occupancy ratios of 0.500 (18):0.500 (18) and 0.512 (17):0.488 (17). The dihedral angles between terminal phenyl rings for the syndone molecules are 23.3 (4), 45.57 (16), 68.46 (16) and 56.5 (3)°. In the crystal, molecules are connected via N—H⋯N, N—H⋯O, O—H⋯O, O—H⋯N and C—H⋯O hydrogen bonds, forming a three-dimensional network.

2,3-Dibromo-3-(5-nitro-2-fur­yl)-1-phenyl­propan-1-one

In the title compound, C13H9Br2NO4, the phenyl and 2-nitrofuran rings are linked by a 2,3-dibromopropanal group, six atoms of which, including a furyl C atom, are disordered over two positions with a site-occupancy ratio of 0.733 (11):0.267 (11). The dihedral angle between the furan [maximum deviation = 0.028 (4) Å] and phenyl rings in the major component is 16.9 (3)°. In the minor component, the corresponding values are 0.87 (4) Å and 23.3 (5)°. In the crystal, intermolecular C—H⋯O hydrogen bonds link the molecules into two-dimensional arrays parallel to the ab plane.

4-[2-(4-Chloro­phen­yl)hydrazinyl­idene]-3-methyl-1H-pyrazol-5(4H)-one

In the title compound, C10H9ClN4O, the pyrazole ring [maximum deviation = 0.014 (2) Å] forms a dihedral angle of 7.06 (14)° with the chlorobenzene ring. The molecular conformation is stabilized by an intramolecular N—H⋯O hydrogen bond, which generates an S(6) ring motif. In the crystal, inversion dimers linked by pairs of C—H⋯O hydrogen bonds generate R 2 2(16) ring motifs. The dimers are further connected by N—H⋯N hydrogen bonds, thereby forming layers lying parallel to the bc plane.

2-Bromo-3-phenyl-1-(3-phenyl-sydnon-4-yl)prop-2-en-1-one.

The title sydnone derivative [systematic name: 2-bromo-1-(5-oxido-3-phenyl-1,2,3-oxadiazolium-4-yl)-3-phenylprop-2-en-1-one], C17H11BrN2O3, exists in a Z configuration with respect to the acyclic C=C bond. An intramolecular C—H⋯Br hydrogen bond generates a six-membered ring, producing an S(6) ring motif. The 1,2,3-oxadiazole ring in the sydnone unit is essentially planar [maximum deviation = 0.011 (2) Å] and forms dihedral angles of 55.39 (13) and 57.12 (12)° with the two benzene rings. In the crystal structure, intermolecular C—H⋯O hydrogen bonds link molecules into two-molecule-thick arrays parallel to the bc plane. The crystal structure also features a short intermolecular N⋯C contacts [3.030 (3) Å] as well as C—H⋯π and π–π interactions [centroid–centroid distances = 3.3798 (11) and 3.2403 (12) Å].

[3-(5-Nitro-2-fur-yl)-1-phenyl-1H-pyrazol-4-yl](phen-yl)methanone.

In the title pyrazole compound, C20H13N3O4, an intramolecular C—H⋯O hydrogen bond generates a seven-membered ring, producing an S(7) ring motif. The essentially planar furan and pyrazole rings [maximum deviations of 0.002 (1) and 0.007 (1) Å, respectively] are coplanar with each other, forming a dihedral angle of 3.06 (10)°. The pyrazole ring forms dihedral angles of 8.51 (9) and 56.81 (9)° with the two benzene rings. The nitro group is coplanar with the attached furan ring, as indicated by the dihedral angle of 2.5 (3)°. In the crystal packing, intermolecular C—H⋯O hydrogen bonds link adjacent molecules into two-molecule-wide chains along the a axis. The crystal packing is further stabilized by weak intermolecular C—H⋯π and π–π interactions [centroid–centroid distance = 3.4441 (10) Å].

2,5-Bis(4-meth-oxy-phen-yl)-1,3,4-oxadiazole.

In the title compound, C16H14N2O3, the essentially planar 1,3,4-oxadiazole ring [maximum deviation = 0.0021 (11) Å] is inclined at dihedral angles of 8.06 (6) and 11.21 (6)° with respect to the two benzene rings; the dihedral angle between the latter rings is 11.66 (5)°. In the crystal, short intermolecular C⋯O interactions [2.9968 (15) Å] connect adjacent molecules into chains propagating in [203]. The crystal structure is further stabilized by weak intermolecular C—H⋯π interactions.