Towards non-peptide ANG II AT1 receptor antagonists based on urocanic acid: rational design, synthesis and biological evaluation.
A series of o-, m- and p-benzyl tetrazole derivatives 11a-c has been designed, synthesized and evaluated as potential Angiotensin II AT1 receptor antagonists, based on urocanic acid. Compound 11b with tetrazole moiety at the m-position showed moderate, however, higher activity compared to the o- and p-counterpart analogues. Molecular modelling techniques were performed in order to extract their putative bioactive conformations and explore their binding modes.
Agelis
George
G
Department of Chemistry, University of Patras, 26500, Patras, Greece. aggelisgeorge@hotmail.com
Resvani
Amalia
A
Matsoukas
Minos-Timotheos
MT
Tselios
Theodore
T
Kelaidonis
Konstantinos
K
Kalavrizioti
Dimitra
D
Vlahakos
Demetrios
D
Matsoukas
John
J
D057911:Angiotensin Receptor Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008297:Male; D008958:Models, Molecular; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D011945:Receptors, Angiotensin / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014560:Urocanic Acid / Q000737:chemistry*
D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D014560:Urocanic Acid