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Chapter 1
Synthesis of functionalized pyrimidines
The pharmacological profile of compounds of the first group was analogous to that of
nifedipine. This suggests that they share a common mechanism of action - blockade of
calcium ion influx.
Brain C. Shook et al. 28 has synthesized a novel series of arylindenopyrimidines
(Figure-12) identified as A 2A and A 1 receptor antagonists. The series was
optimized for vitro activity by substituting the 8-and-9- positions with methylene
amine substituents. The compounds show excellent activity in mouse models of
parkinson’s disease when dosed orally.
O
Ar
R'RN
N
Figure-12
N
NH 2
1.3. Synthetic strategies for the dihydropyrimidines (DHPMs)
Having tremendous important of DHPMs in medicinal chemistry, a literature
survey on the synthetic methods for the biologically active dihydropyrimidines
(DHPMs) has been carried out and described as follows. Various modifications have
been applied to Biginelli reaction to get better yield and to synthesize biologically
active analogs. Different catalysts have been reported to increase the yield of the
reaction. Microwave synthesis strategies have also been applied to shorten the
reaction time. Solid phase synthesis and combinatorial chemistry has made possible to
generate library of DHPM analogs. The various modifications are discussed in the
following section.
Catalysts
Min Yang and coworkers 29 have synthesized the different DHPMs by using
various inorganic salts as a catalyst (Figure-13). They found that the yields of the
one-pot Biginelli reaction can be increased from 20-50% to 81-99%, while the
reaction time shorted for 18-24 hrs to 20-30 min. This modification was developed by
using Yb(OTf) 3 and YbCl 3 as a catalyst under solvent free conditions. One additional
important feature of this protocol is the catalyst can be easily recovered and reused.
Department of Chemistry, Saurashtra University, Rajkot-360005 7