Facile and efficient syntheses of a series of N-benzyl and N-biphenylmethyl substituted imidazole derivatives based on (E)-urocanic acid, as Angiotensin II AT1 receptor blockers
In the present work, a facile and efficient route for the synthesis of a series of
N-substituted imidazole derivatives is described. Docking studies have revealed that
N-substituted imidazole derivatives based on (E)-urocanic acid may be potential
antihypertensive leads. Therefore, new AT1 receptor blockers bearing either the benzyl or
the biphenylmethyl moiety at the N-1 or N-3 position, either the (E)-acrylate or the
propanoate fragment and their related acids at the C-4 position as well as a halogen atom at
the C-5 position of the imidazole ring, were synthesized. The newly synthesized analogues
were evaluated for binding to human AT1 receptor. The biological results showed that this
class of molecules possesses moderate or no activity, thus not always confirming high
docking scores. Nonetheless, important conclusions can be derived for their molecular
basis of their mode of action and help medicinal chemists to design and synthesize more
potent ones. An aliphatic group as in losartan seems to be important for enhancing binding
affinity and activity