A new series of thiazolo[3,2-a]pyrimidine bromide salt derivatives 7a–d were synthesized from 3,4-dihydropyrimidinethione precursors. The target compounds were fully characterized by 1D- and 2D-NMR, high resolution ESI-MS/MS and single crystal X-ray diffraction analysis, which confirmed a regioselective 5H cyclization of the dihydropyrimidinethiones. All target compounds were evaluated in vitro as human acetylcholinesterase (hAChE) inhibitors via an Ellman-based colorimetric assay and showed good inhibition activities (better than 70% at 10 µM and IC₅₀ values in the 1 µM range). Molecular docking simulations for all target products into hAChE were performed and confirmed strong binding to the enzyme. These results provide a promising and new starting point to improve acetylcholinesterase inhibitors and explore novel treatment options against Alzheimer’s disease.

Synthesis of 3,4-dihydropyrimidin-2(1H)-one and 3,4-dihydropyrimidin-2(1H)-thione derivatives from aldehydes, 1,3-dicarbonyl derivatives and urea or thiourea using granite and quartz as new, natural and reusable catalysts. Some of the 3,4-dihydropyrimidin-2(1H)-thione derivatives were used to prepare new heterocyclic compounds. The antimicrobial activity of selected examples of the synthesized compounds was tested and showed moderate activity.

1, 2-dithiol 3-thione derivatives, as starting materials, were subjected to cycloaddition reactions in the presence of the dried outer shell of shrimp (chitin), under different reaction conditions to produce the 1, 3-dithiole-2-ylidene system. On treating 4-bromo dithiol 3-one, with dimethyl ester of acetylene dicarboxylic acid the bromo oxothiafulvene was produced. Further addition of DMAD to bromotrithiafulvene afforded the spiro bromo derivative. Trithiones and trithiafulvenes were also added to quinones, cyclohexadiene and cyclopentadiene monomer, and the corresponding adducts were produced through 1,3-dipole cycloaddition reactions. On testing some of the products against the isolated micro-organisms from sugar cane factory, the inhibition zones at concentration 1 × 10⁻⁶ were found. Products (2, 6, 9, 16, 23, 25, and 26) showed high activities against Bacillus sub., E.Coli and Asper. Niger.

Acetylcholinesterase (AChE) is the enzyme that catalyzes the hydrolysis of the neurotransmitter acetylcholine (ACh) into acetic acid and choline, a crucial mechanism for regulation of neurotransmission at synapses in all nervous systems. According to the cholinergic hypothesis, depleted levels of ACh are associated with Alzheimer's disease. As part of a program aimed at preparing new bioactive heterocycles with kinase and AChE inhibition properties, we designed and synthesized a series of (Z)-2-arylidene- and 2-aminomethylene derivatives of thiazolo[3,2-a]pyrimidine by a convenient multicomponent method. The products were fully characterized by 1D- and 2D-NMR, high resolution ESI-MS/MS and single crystal X-ray diffraction analysis, which indicated a consistent Z configuration at the arylidene and amino methylene double bond. Additionally, molecular docking simulations of the series of 2-arylidene/aminomethylene-thiazolo[3,2-a]pyrimidine derivatives to human AChE (PDB ID: 4m0f, chain A) were conducted to investigate the binding mode of those compounds in comparison to Territrem B, used as positive control. The results indicate that some of the test compounds have binding energies to AChE that are comparable, or better, than the positive control, Territrem B. Biological activity studies are underway to assess the activities of the new compounds [1-4]. References: Francis, P.; Palmer, A.; Snape, M.; Wilcock, G. Neurol. Neurosurg. Psychiatry 1999, 66, 137-147. Zhi, H.; Chen, L.; Zhang, L.; Liu, S.-j.; Wan, D. C. C.; Lin, H.; Hu, C. Arkivoc 2008, 13, 266-277. Jin, C.H.; Jun, K.Y.; Lee, E.; Kim, S.; Kwon, Y.; Kim, K.; Na, Y. Med. Chem. 2014, 22, 4553-4565. Cheung, J.; Gary, E. N.; Shiomi, K.; Rosenberry, T. L. ACS Med. Chem. Lett. 2013, 4, 1091-1096.