Cholinesterase Inhibitory Activities of N-Phenylthiazol-2-Amine Derivatives and their Molecular Docking Studies.

Alzheimer's disease (AD) is a type of neurodegenerative disorder which is responsible for many cognitive dysfunctions. According to the most accepted cholinergic hypothesis, cholinesterases have a major role in AD symptoms. The use of small molecules as inhibitors is one of the most useful strategies to control AD. In the present work, a series of N-phenylthiazol-2-amine derivatives was screened against acetylcholinesterase (AChE) from Electrophorus electricus and butyrylcholinesterase (BChE) from horse serum by using Ellman's method, using neostigmine and donepezil as reference drugs. Some of the assayed compounds proved to be potent inhibitors for AChE and BChE activity. N-(2,3-dimethylphenyl)thiazol-2-amine, 3j was found to be the most active inhibitor among the series with IC50 value of 0.009 ± 0.002 µM and 0.646 ± 0.012 µM against AChE and BChE, respectively. Molecular docking studies were carried out in order to better understand the ligand binding site interactions.

N-(2,4-Dichloro-phen-yl)-1,3-thia-zol-2-amine.

In the title mol-ecule, C(9)H(6)Cl(2)N(2)S, the mean planes of the benzene and thia-zole rings make a dihedral angle of 54.18 (8)°. In the crystal, mol-ecules are joined into dimers with an R(2) (2)(8) ring motif by pairs of N-H⋯N hydrogen bonds. These dimers are linked by C-H⋯Cl inter-actions into layers parallel to (011). The thia-zole rings form columns along the c-axis direction, with a centroid-centroid separation of 3.8581 (9) Å, indicating π-π inter-actions. An intra-molecular C-H⋯S contact also occurs.

N-(2,4,6-Trimethyl-phen-yl)-1,3-thia-zol-2-amine.

In the title compound, C(12)H(14)N(2)S, the dihedral angle between the 1,3,5-trimethyl-benzene and 1,3-thia-zol-2-amine groups is 73.15 (4)°. In the crystal, inversion dimers linked by pairs of N-H⋯N hydrogen bonds generate R(2) (2)(8) loops.