Shobhitha Shetty

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.

Dimethyl 2-[2-(2,4,6-tri-chloro-phen-yl)hydrazin-1-yl-idene]butane-dioate.

In the title compound, C12H11Cl3N2O4, the dihedral angle between the aromatic ring and the hydrazine (NH—N=C) grouping is 52.2 (3)°. The butanedioate groups exhibit planar conformations. An intramolecular N—H⋯O hydrogen bond links the N—H group of the hydrazine to one of the methoxy groups of the butanedioate moiety. In the crystal, molecules are linked by C—H⋯O hydrogen bonds and π–π interactions are also observed [centroid–centroid separation = 3.535 (1) Å].

2,3-Dibromo-3-(4-chloro-phen-yl)-1-(4-nitro-thio-phen-2-yl)propan-1-one.

The title compound, C13H8Br2ClNO3S, exhibits whole-molecule disorder over two orientations in a 0.805 (6):0.195 (6) ratio. The dihedral angles between the thiophene ring [maximum deviations = 0.017 (4) and 0.033 (9) Å for the major and minor components, respectively] and the chloro-substituted phenyl ring are 32.1 (5) (major component) and 26.3 (18)° (minor component). In the crystal, C—H⋯Cl and C—H⋯O hydrogen bonds link the molecules into sheets lying parallel to the bc plane. Aromatic π–π stacking interactions [centroid–centroid distance = 3.550 (7) Å] are also observed.

(2E)-2-[(3-Methyl-5-phen­oxy-1-phenyl-1H-pyrazol-4-yl)methyl­idene]hydrazinecarbothio­amide

In the title compound, C18H17N5OS, the mean plane of the pyrazole ring [maximum deviation = 0.0031 (12) Å] forms dihedral angles of 19.6 (4) and 9.3 (5)° with the two disorder components of the N-bound benzene ring (with equal occupancies for the two orientations) and a dihedral angle of 72.58 (8)° with the C—O-bonded benzene ring. The molecule exists in a trans conformation with respect to the N=C bond [1.2792 (19) Å]. The molecular structure features an intramolecular C—H⋯O hydrogen bond, forming an S(6) ring. In the crystal, N—H⋯N and N—H⋯S hydrogen bonds result in the formation of zigzag layers lying parallel to (10-1).

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.

3-Methyl-5-phen-oxy-1-phenyl-1H-pyrazole-4-carbaldehyde.

In the title compound, C17H14N2O2, the pyrazole ring makes dihedral angles of 73.67 (4) and 45.99 (4)°, respectively, with the adjacent phenyl and phenoxy rings. In the crystal, there are no classical hydrogen bonds, but a weak C—H⋯π interaction is observed.

Ethyl 2-[2-(2-methoxyphenyl)hydrazinylidene]-3-oxobutanoate

In the title compound, C13H16N2O4, an intramolecular N—H⋯O hydrogen bond generates an S(6) ring. The molecule adopts an E configuration with respect to the central C=N double bond. In the crystal, symmetry-related molecules are connected into chains along [010] via weak C—H⋯N hydrogen bonds. The crystal structure is further stabilized by weak C—H⋯π interactions.

3-Methyl-5-oxo-4-(2-phenyl-hydrazinyl-idene)-4,5-dihydro-1H-pyrazole-1-carbothio-amide.

In the title compound, C11H11N5OS, the pyrazole ring is approximately planar, with a maximum deviation of 0.010 (2) Å. The dihedral angles between the benzene ring and the pyrazole and carbothioamide groups are 5.42 (9) and 10.61 (18)°, respectively. An intramolecular N—H⋯O hydrogen bond generates an S(6) ring motif. In the crystal, molecules are connected by intermolecular N—H⋯O and C—H⋯S hydrogen bonds, forming R 2 2(12) ring motifs. In addition, there is a π–π stacking interaction [centroid–centroid distance = 3.5188 (11) Å] between the pyrazole and benzene rings. These interactions link the molecules into infinite chains along [001].

2,3-Dibromo-1,3-bis­(4-chloro­phen­yl)propan-1-one

In the title compound, C15H10Br2Cl2O, the terminal benzene rings make a dihedral angle of 31.1 (2)° with each other. In the crystal, molecules are stacked along the a axis and consolidated by C—H⋯π interactions. Short Cl⋯Cl [3.1140 (17) Å] and Br⋯Cl [3.4565 (13) Å] contacts are observed.

2,3-Dibromo-1-(4-chloro-phen-yl)-3-(5-nitro-2-fur-yl)propan-1-one.

In the title compound, C13H8Br2ClNO4, the linking –CHBr–CHBr– fragment is disordered over two orientations with refined site occupancies of 0.512 (11) and 0.488 (11). The dihedral angle between the furan ring and the phenyl ring is 21.86 (16)°. In the crystal, the molecules are linked into [011] chains by intermolecular C—H⋯O hydrogen bonds.