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Chapter 1
Synthesis of functionalized pyrimidines
Bryzgalov A. O. et al. has studied the antiarrhythmic activity of 4,6-
di(het)aryl-5-nitro-3,4-dihydropyrimidin-(1H)-2-ones (Figure-10) toward two types
of experimental rat arrhythmia. With CaCl 2 induced arrhythmia model, several agents
have demonstrated high antiarrhythmic activity and the lack of influence on arterial
pressure of rats. 26 Figure 10
Remennikov G. et al. 27 has synthesized some novel 4-aryl-5-nitro substituted
DHPMs (Figure 11) using nitro acetone and screened as calcium modulators. They
have studied the pharmacological properties of 6-methyl- and 1,6-dimethyl-4-aryl-5-
nitro-2-oxo-l,2,3,4-tetrahydropyrimidines with different substituents in the aryl
fragment, i.e. unsubstituted, ortho, meta, para, di, and tri-substituted compounds and
observed that 5-nitro DHPMs bearing unsubstituted, ortho and tri-substitution on aryl
moieties at C4 position reduced blood pressure and inhibited myocardial contractile
activity. The second group consisted meta, para and di-substituted aryl moieties with
DHPMs increased blood pressure and had positive inotropic effects. The compounds
with the highest hypotensive activity were containing substituent in the ortho position
of the phenyl fragment. Thus, compounds having substitution on aryl moieties which
had pronounced vasodilator and weak cardio depressive actions, increased cardiac
pump function (SV). When inhibition of myocardial contractile function
predominated, there was a reduction in SV. The effect of compounds of the first group
on heart rate was variable, though most reduced heart rate. In addition, a reflex
increase in heart rate might be expected because of the reduction in blood pressure.
The reference preparations for compounds of this group were the calcium antagonist
nifedipine.
Figure-11
Department of Chemistry, Saurashtra University, Rajkot-360005 6