Agelis, George published the artcileRational design, efficient syntheses and biological evaluation of N,N’-symmetrically bis-substituted butylimidazole analogs as a new class of potent Angiotensin II receptor blockers, Category: imidazoles-derivatives, the publication is European Journal of Medicinal Chemistry (2013), 352-370, database is CAplus and MEDLINE.
A series of sym. bis-substituted imidazole analogs bearing at the N-1 and N-3 positions two biphenyl moieties ortho substituted either with tetrazole or carboxylate functional groups was designed based on docking studies and utilizing for the first time an extra hydrophobic binding cleft of the AT1 receptor. The synthesized analogs were evaluated for their in vitro antagonistic activities (pA2 values) and binding affinities (-logIC50 values) to the Angiotensin II AT1 receptor. Among them, the dipotassium (-logIC50 = 9.04) and the disodium (-logIC50 = 8.54) salts of 4-butyl-N,N’-bis{[2′-(2H-tetrazol-5-yl)biphenyl-4-yl]methyl}imidazolium bromide (I) as well as the bis-ortho-carboxylic acid derivative (-logIC50 = 9.46) and 4-butyl-2-hydroxymethyl-N,N’-bis{[2′-(2H-tetrazol-5-yl)biphenyl-4-yl]methyl}imidazolium bromide (-logIC50 = 8.37, pA2 = 8.58) showed high binding affinity to the AT1 receptor and high antagonistic activity (potency). The potency was similar or even superior to that of Losartan (-logIC50 = 8.25, pA2 = 8.25). On the contrary, 2-butyl-N,N’-bis{[2′-[2H-tetrazol-5-yl]biphenyl-4-yl]methyl}imidazolium bromide (-logIC50 = 5.77) and 2-butyl-4-chloro-5-hydroxymethyl-N,N’-bis{[2′-[2H-tetrazol-5-yl]biphenyl-4-yl]methyl}imidazolium bromide (-logIC50 = 6.38) displayed very low binding affinity indicating that the orientation of the Bu group is of primary importance. Docking studies of the representative highly active I·2Na clearly showed that this mol. has an extra hydrophobic binding feature compared to prototype drug Losartan and it fits to the extra hydrophobic cavity. These results may contribute to the discovery and development of a new class of biol. active mols. through bis-alkylation of the imidazole ring by a convenient and cost effective synthetic strategy.
European Journal of Medicinal Chemistry published new progress about 79047-41-9. 79047-41-9 belongs to imidazoles-derivatives, auxiliary class Imidazole,Chloride,Alcohol, name is (2-Butyl-4-chloro-1H-imidazol-5-yl)methanol, and the molecular formula is C8H13ClN2O, Category: imidazoles-derivatives.
Referemce:
https://en.wikipedia.org/wiki/Imidazole,
Imidazole | C3H4N2 – PubChem