Conformational and biological studies for a pair of novel synthetic AT1 antagonists: stereoelectronic requirements for antihypertensive efficacy.
One of the major systems which interferes with the disease of hypertension, is the Renin Angiotensin Aldosterone System (RAS). The octapeptide hormone angiotensin II is the active product of RAS which causes vasoconstriction when binds to the AT(1) receptor. In the last years, there has been a development of drugs which block the Angiotensin II from binding the AT(1) receptor and are called AT(1) antagonists. In an effort to comprehend their stereoelectronic features, a study has been initiated to compare the conformational properties of drugs already marketed for the treatment of hypertension and others which are designed and synthesized in our laboratory possessing structural characteristics necessary for antihypertensive activity. In this study, two synthetic non-peptide AT(1) antagonists, are structurally elucidated and their conformational properties and bioactivity are compared to the prototype and first approved drug of this category in the market; losartan (trade name: COZAAR).
Zoumpoulakis
P
P
Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, Vas Constantinou 48, 11635, Athens, Greece.
Zoga
A
A
Roumelioti
P
P
Giatas
N
N
Grdadolnik
S G
SG
Iliodromitis
E
E
Vlahakos
D
D
Kremastinos
D
D
Matsoukas
J M
JM
Mavromoustakos
T
T
D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019808:Losartan / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001593:Benzyl Compounds; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D019808:Losartan