Download (6Mb) - Etheses - Saurashtra University

Chapter 1
Synthesis of functionalized pyrimidines
Barrow et al. has reported in vitro and in vivo evaluation of
dihydropyrimidinone C-5 amides as potent and selective r1A receptor antagonists for
the treatment of benign prostatic hyperplasia (Figure-5). R1 Adrenergic receptors
mediate both vascular and lower urinary tract tone, and R1 receptor antagonists such
as terazosin are used to treat both hypertension and benign prostatic hyperplasia
(BPH). Recently, three different subtypes of this receptor have been identified, with
the R1A receptor being most prevalent in lower urinary tract tissue. Barrow et al. has
also reported 4-aryldihydropyrimidinones attached to an aminopropyl-4-
arylpiperidine via a C5 amide as selective R1A receptor subtype antagonists. In
receptor binding assays, these types of compounds generally display Ki values for the
R1a receptor subtype 20%) and half-life (>6 h) in
both rats and dogs. Due to its selectivity for the R1a over the R1b and R1d receptors
as well as its favorable pharmacokinetic profile, it has the potential to relieve the
symptoms of BPH without eliciting effects on the cardiovascular system. 21,22
F
F
N
R 3 R 2
Figure-5
The 4-aryldihydropyrimidinone attached to an aminopropyl-4-arylpiperidine
via a C5 amide has proved to be an excellent template for selective R1A receptor
subtype antagonists. Those compounds are exceptionally potent in both cloned
receptor binding studies as well as in vivo pharmacodynamic models of prostatic tone.
Atwal et al. have examined a series of novel dihydropyrimidine calcium
channel blockers that contain a basic group attached to either C5 or N3 of the
heterocyclic ring (Figure-6).
N
H
O
R 1
N
H
NH
O
Department of Chemistry, Saurashtra University, Rajkot-360005 3