M. Sarfraz

(E)-2,3-Dimethyl-N-(2-nitro­benzyl­idene)aniline

In the title compound, C15H14N2O2, the 2,3-dimethylanilinic and benzaldehyde groups are planar, with r.m.s. deviations of 0.0101 and 0.0241 Å, respectively, and are oriented at a dihedral angle of 11.69 (3)°. The nitro group is inclined to the benzaldehyde group by 34.02 (9)°. The molecule adopts an E configuration about the C=N bond. In the crystal, molecules are linked via C—H⋯O interactions, giving rise to the formation of zigzag polymeric chains extending along [010]. They are also linked by C—H⋯π, and π–π interactions [centroid–centroid distance of 3.7185 (11) Å] involving symmetry-related aniline and benzene rings. The H atoms of the ortho-methyl group are disordered over two sites with a refined occupancy ratio of 0.69 (2):0.31 (2).

N-[(E)-4-Chloro­benzyl­idene]-2,3-dimethyl­aniline

In the title compound, C15H14ClN, the conformation about the C=N bond is trans and the dihedral angle between the aromatic rings is 51.48 (4)°. In the crystal, some very weak C—H⋯π interactions may help to establish the packing.

Synthesis, biological evaluation and docking studies of 2,3-dihydroquinazolin-4(1H)-one derivatives as inhibitors of cholinesterases

In search of potent inhibitors of cholinesterases, we have synthesized and evaluate a number of 2,3-dihydroquinazolin-4(1H)-one derivatives. The synthetic approach provided an efficient synthesis of the target molecules with excellent yield. All the tested compounds showed activity against both the enzymes in micromolar range. In many case, the inhibition of both enzymes are higher than or comparable to the standard drug galatamine. With the selectivity index of 2.3 for AChE, compound 5f can be considered as a potential lead compound with a feature of dual AChE/BChE inhibition with IC50=1.6±0.10μM (AChE) and 3.7±0.18μM (BChE). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. The computed binding modes of these compounds in the active site of AChE and BChE provide an insight into the mechanism of inhibition of these two enzyme.

(E)-1-(4-Meth-oxy-benzyl-idene)-2-phenyl-hydrazine.

In the title compound, C14H14N2O, the dihedral angle between the aromatic rings is 9.30 (6)°. In the crystal, molecules are linked by C—H⋯π and N—H⋯π interactions.

Synthesis, crystal structure determination, biological screening and docking studies of N 1 -substituted derivatives of 2,3-dihydroquinazolin-4(1 H )-one as inhibitors of cholinesterases

Pursuing the strategy of developing potent AChE inhibitors, we attempted to carry out the N1-substitution of 2,3-dihydroquinazolin-4(1H)-one core. A set of 32 N-alkylated/benzylated quinazoline derivatives were synthesized, characterized and evaluated for their inhibition against cholinesterases. N-alkylation of the series of the compounds reported previously (N-unsubstituted) resulted in improved activity. All the compounds showed inhibition of both enzymes in the micromolar to submicromolar range. Structure activity relationship (SAR) of the 32 derivatives showed that N-benzylated compounds possess good activity than N-alkylated compounds. N-benzylated compounds 2ad and 2af were found very active with their IC50 values toward AChE in submicromolar range (0.8µM and 0.6µM respectively). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. Computational predictions of ADMET studies reveal that all the compounds have good pharmacokinetic properties with no AMES toxicity and carcinogenicity. Moreover, all the compounds are predicted to be absorbed in human intestine and also have the ability to cross blood brain barrier. Overall, the synthesized compounds have established a structural foundation for the design of new inhibitors of cholinesterase.

N-{(E)-[4-(Dimethyl­amino)­phen­yl]methyl­idene}-2,3-dimethyl­aniline

There are two independent molecules in the asymmetric unit of the title compound, C17H20N2, in which the dihedral angles between the aromatic rings are 30.34 (11) and 41.44 (8)°. In the crystal, weak C—H⋯π interactions may help to establish the packing.

(E)-1-(2-Nitro-benzyl-idene)-2-phenyl-hydrazine.

The asymmetric unit of the title compound, C13H11N3O2, contains two molecules with slightly different conformations: the dihedral angle between the aromatic rings is 13.01 (10)° in one molecule and 14.05 (10)° in the other. Both molecules feature short intramolecular C—H⋯O contacts, which generate S(6) rings. In the crystal, both molecules form inversion dimers linked by pairs of N—H⋯O hydrogen bonds, thereby generating R 2 2(16) rings.

(2Z)-2-[(2,3-Dimethyl-phen-yl)imino]-1,2-diphenyl-ethanone.

In the title compound, C22H19NO, the 2,3-dimethylanilinic group is planar with an r.m.s. deviation of 0.0226 Å. The phenyl rings with the carbonyl and imine substituents are also planar with r.m.s. deviations of 0.0019 and 0.0048 Å, respectively. These phenyl rings are oriented at dihedral angles of 74.70 (5) and 79.43 (5)°, respectively, with the 2,3-dimethylanilinic group, whereas the dihedral angle between them is 88.28 (4)°. Weak intramolecular C—H⋯N hydrogen bonding occurs and completes an S(5) ring motif in the molecule. In the crystal, weak π–π interactions are present between the carbonyl-containing phenyl rings at a centroid–centroid distance of 3.5958 (12) Å. C—H⋯π interactions between the 2,3-dimethylanilinic and the carbonyl-containing phenyl rings are also present, where the C—H group is from the former.

2-[(E)-(2,3-Dimethyl­phen­yl)imino­meth­yl]phenol

In the title compound, C15H15NO, the almost planar 2,3-dimethylaniline unit and the salicylaldehyde group (r.m.s. deviations of 0.0156 and 0.0109 Å, respectively) are oriented at a dihedral angle of 43.69 (9)° with respect to each other. An S(6) ring motif is formed due to intramolecular O—H⋯N hydrogen bonding. In the crystal, C—H⋯π interactions occur between the 2,3-dimethylaniline unit and the salicylaldehyde group, where the CH is from the o-methyl group.

2,3-Dimethyl-N-[(E)-(1H-pyrrol-2-yl)methyl­idene]aniline

In the title compound, C13H14N2, the dihedral angle between the aromatic rings is 69.73 (14)°. In the crystal, inversion dimers linked by pairs of N—H⋯N hydrogen bonds generate R 2 2(10) loops. A weak C—H⋯π interaction also occurs.