Synthesis of novel nitric oxide (NO)-releasing esters of timolol.
A novel class of timolol derivatives with nitric oxide (NO)-donating moieties achieved chemical stability yet under physiologically relevant conditions released timolol and NO. Hindered esters A were designed and synthesized, whose 'triggered' release relied on enzymatic hydrolysis of the nitrate ester in A to B, that in turn cyclized to liberate timolol.
NicOx Research Institute, Bresso, Milan, Italy. chiroli@nicox.it
Valerio
V
Chiroli
Minerva R
MR
Batugo
Stefano
S
Biondi
Annalisa
A
Bonfanti
Stefania
S
Brambilla
David C
DC
Gale
Lin
L
Li
Daniela
D
Miglietta
Fabio
F
Nicoli
Ganesh A
GA
Prasanna
Daniela
D
Ronchetti
William F
WF
Vernier
Wesley K M
WK
Chong
D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D004355:Drug Stability; D004952:Esters / Q000737:chemistry / Q000378:metabolism; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D013999:Timolol / Q000737:chemistry*
D000319:Adrenergic beta-Antagonists; D004952:Esters; D009569:Nitric Oxide; D013999:Timolol; D006162:Guanylate Cyclase