Design and synthesis of novel antihypertensive drugs.
AT1 antagonists constitute a new generation of drugs for the treatment of hypertension and are designed and synthesized to mimic the C-terminal segment of Angiotensin II (Ang II) and to block its binding action on AT1 receptor. For this reason, the conformational analysis of Ang II and its derivatives as well as the AT1 antagonists belonging to SARTANs class of molecules were studied. Such studies offer the possibility to reveal the stereoelectronic factors responsible for bioactivity of AT1 antagonists and to design and synthesize new analogues with better pharmacological and financial profiles. An example of a novel synthetic non-peptide molecule is given which mimics the His(6)-Pro(7)-Phe(8) part of Ang II and is based on the (S)-pyroglutamic acid.
University of Athens, Department of Chemistry, Zographou 15771, Greece.
P
P
Moutevelis-Minakakis
M
M
Gianni
H
H
Stougiannou
P
P
Zoumpoulakis
A
A
Zoga
A D
AD
Vlahakos
E
E
Iliodromitis
T
T
Mavromoustakos
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000737:chemistry; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D011760:Pyrrolidinones / Q000737:chemistry
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D011760:Pyrrolidinones; D000804:Angiotensin II