Utility of Activated Nitriles in the Synthesis of Novel Heterocyclic Compounds with Antitumor Activity

Abstract

Reaction of cyanoacetic acid hydrazide (1) with 4-methoxyacetophenone and 4-chlorobenzaldehyde (2a,b) afforded the corresponding 2-cyanoacetohydrazide derivatives (3a,b) respectively. The latter compounds were utilized as a key intermediate for the synthesis of new heterocyclic compounds. Newly synthesized compounds were characterized by elemental analyses and spectral data. The antitumor evaluation of some newly synthesized compounds was screened in vitro against human breast cancer cell line (MCF-7).

Synthesis and Spectral Study of some New α, β-Unsaturated Carbonyl Compounds and Pyrazole Derivatives

“…Preparation of α, β-Unsaturated Carbonyl Compound A 11 (Salman, 2013) Adding the KOH (0.56 g, 0.01mol) suspended in dry DMF (10 ml) to hydrazine hydrazone A 2 (2.31g, 0.01mol) with stirring continues for (30 min), then phenylisothiocyanate (1.35 g, 0.01mol) was added gradually to the reaction mixture with continuous stirring for (12 hours) at room temperature to form an intermediate compound followed by the addition of ethyl chloro acetate (1.22 g, 0.01mol) with continuous stirring for (6 hours). The reaction mixture is poured over crushed ice with stirring, and the precipitate formed is separated by filtration, then leave to dry and recrystallized with ethanol/DMF, the result is dark yellow, m.p (175-173 °C), yield (63%).…”

Pyrido[2,3-d]pyrimidin-7(8H)-ones: Synthesis and Biomedical Applications

“…Once more, such pattern substitution relates to the different biological activities these two families of structures have been oriented towards. [36,76] In summary, the combinations of substituents apparently more widely explored in literature for both structures are a) In 14.08% of the 5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones (11): G 2 = nitrogen substituent, G 4 = oxygen substituent (in particular as a carbonyl group), R 5 = phenyl group, R 6 Thus, in the case of the structures 11 (C5-C6 single bond), 53.12% present at least a substituent at C5 and a CH2 at C6 (in most of them a carbon substituent [29,30] and, more precisely, a phenyl ring in one half of the structures [50,51]) while only 3.19% present a substituent at C6 and a CH2 at C5 (in this case most structures present a carbon substituent [52,53] which is a phenyl ring in also one half of them [31,42]). Finally, 20.86% of the structures do not present substituents at C5 or C6 [20,54].…”

“…Once more, such pattern substitution relates to the different biological activities these two families of structures have been oriented towards. [36,76] In summary, the combinations of substituents apparently more widely explored in literature for both structures are a) In 14.08% of the 5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones (11): G 2 = nitrogen substituent, G 4 = oxygen substituent (in particular as a carbonyl group), R 5 = phenyl group, R 6 [36,76] In summary, the combinations of substituents apparently more widely explored in literature for both structures are Although the differences in the substitution pattern of 5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones (11) and pyrido[2,3-d]pyrimidin-7(8H)-ones (10) could be attributed initially to the greater or lesser synthetic accessibility of some types of substituents, the different orientation of the biological activities sought for each structure seem to be the ultimate reason for such diversity.…”