A new and efficient synthesis of substituted 6-[(2′-Dialkylamino)ethyl] pyrimidine and 4- N,N -Dialkyl-6-vinyl-cytosine derivatives and evaluation of their anti-Rubella activity

Towards new methodologies for the synthesis of biologically interesting 6-substituted pyrimidines and 4(3H)-pyrimidinones

“…All the synthesized compounds were submitted to biological evaluation as HIV-1 RT inhibitors according to a previously described procedure. 54 Compounds 48a and 48b were proved to inhibit the wild type RT with nM and µM potency, respectively, acting with a new competitive mechanism never reported in the literature for this class of compounds. 57,58 However, details of this mechanism remain still unknown.…”

“…Title compounds 13-15, 23-38, a new family of S-DABOs characterized by the presence of an arylalkylthio substitution at C-2, a methyl group at C-5, and a halogenated benzyl group at C-6 of the pyrimidinone nucleus, were prepared in a straightforward fashion by alkylation of three different 6-substituted 2-thiouracils (20)(21)(22) and subsequent oxidation of the sulfur atom (13, 37, and 38). [48][49] The new compounds were evaluated in enzymatic tests for their ability to inhibit either wild-type (wt) or mutated RTs as well as on MT-4 cells for cytotoxicity and anti-HIV-activity, in comparison with nevirapine (nev) and efavirenz (efa), used as reference drugs.…”

“…For the synthesis of target compounds 48a-k, the approach described in Scheme 6 was initially followed, 54 essentially based on the activation of the alcohol moiety of pyrimidinone 45 followed by nucleophilic displacement of the activated hydroxy group with a series of different amines. A deeper analysis of IR and NMR spectra of compound 46 raised the doubt about its real structure even if a previously detailed job [54][55] assigned the structure drawn in Scheme 6.…”

“…A deeper analysis of IR and NMR spectra of compound 46 raised the doubt about its real structure even if a previously detailed job [54][55] assigned the structure drawn in Scheme 6. In our mind, the tosylation reaction was more likely to be occurred on the C-4 OH rather than on the primary hydroxy group as initially supposed.…”

“…Finally, X-Ray crystallographic analysis of 46 ( Figure 9) confirmed this assumption; definitely assigning to the tosyl derivative the structure 49 (Scheme 7). As a result, all compounds previously synthesized [53][54][55] have the general structure 50 instead of 47 ( Figure 10). …”