The advantages of the catalyst were better yields and do not require dry solvents. The first step in the mechanism of the Biginelli reaction is the acid-catalyzed condensation of the urea with the aldehyde. This reaction begins with protonation of the aldehyde by the acid and is followed by an attack buy Crizotinib of the amine from urea. Proton transfer steps, then result in a protonated alcohol which leaves as water to form an N-acyliminium ion intermediate [31], subsequently enol form of the β-keto ester attacks the N-acyliminium ion to generate an open chain ureide which readily cyclizes to a tetrahydropyrimidines. The reaction times were found to be 12 min. The IR spectra of compounds (4a–l)
showed strong absorption bands for the amine group (3233–3373 cm−1), amide group (1672–1684 cm−1), aliphatic C H stretching (2926–2994 cm−1), aromatic C H stretching (3134–3212 cm−1) and aromatic C C stretching (1539–1591 cm−1). 1H NMR spectrum of compounds 4a–l showed a methyl group protons singlet at (2.01–2.09 ppm), CH-R protons singlet at (5.34–5.52 ppm), aromatic protons triplet at (6.84–7.30 ppm) and amine protons singlet at (9.07–10.18 ppm). The mass spectra and
elemental analysis results were within ±0.6% of the theoretical values. Totally, twelve compounds (4a–l) various substituted 1,2,3,4-tetrahydropyrimidines, were synthesized with the yield ranging from 70% to 83%. These conditions enable this method to be applicable for the synthesis of 1,2,3,4-tetrahydropyrimidines based heterocyclic compounds. selleck chemicals llc The present protocol best describes the synthesis of 1,2,3,4-tetrahydropyrimidines. All the reported 1,2,3,4-tetrahydropyrimidines compounds were found to be novel and not reported elsewhere. Among the novel substituted 1,2,3,4-tetrahydropyrimidine derivatives for treating AD, their anti-cholinesterase activities (compounds 4a–l) was assayed according to Ellman’s method on acetyl cholinesterase
(AChE) from electric eel using commercial donepezil Paclitaxel mouse HCl as the reference standard [32] and [33]. The butyls cholinesterase’s (BuChE) inhibitory on equine serum BuChE were also examined by the same method. Inhibition of AChE activities of the synthesized compounds is shown in Fig. 2 and Table 1. The data listed in Fig. 2 and Table 1 clearly shows that most of the designed compounds exhibited good to moderate inhibitory activities toward the AChE and BuChE inhibition are summarized in Fig. 2 and Table 1. All the synthesized 1,2,3,4-tetrahydropyrimidine derivatives were potent inhibitors of AChE, with IC50 values ranging from micro molar to sub-micro molar. Especially, compound 4l showed the best AChE and BuChE inhibitory activity of all the 1,2,3,4-tetrahydropyrimidine derivatives, with an IC50 value of 0.11 μM and 3.4 μM. Among the compounds reported herein, compound 4l is arguably the most potent.