NO-sartans: a new class of pharmacodynamic hybrids as cardiovascular drugs.
The aim of this work was to develop lead pharmacodynamic hybrids, NO-sartans, possessing the characteristics of a typical AT1-antagonist and of a "slow NO donor", by adding NO-donor side chains to losartan. These new compounds, 2a and 2b, displayed vasorelaxing effects, due to the release of NO, and antagonized the vasocontractile effects of angiotensin II, with potency values similar to that of losartan. In vivo, the antihypertensive effects of 2a were similar to those of losartan and captopril.
Breschi
Maria C
MC
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
Calderone
Vincenzo
V
Digiacomo
Maria
M
Martelli
Alma
A
Martinotti
Enrica
E
Minutolo
Filippo
F
Rapposelli
Simona
S
Balsamo
Aldo
A
D047228:Angiotensin II Type 1 Receptor Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D019808:Losartan / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D019808:Losartan