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 CP-868596 datasheet 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. IDH inhibition 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 Thymidylate synthase 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.