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.
Chiroli
Valerio
V
NicOx Research Institute, Bresso, Milan, Italy. chiroli@nicox.it
Batugo
Minerva R
MR
Biondi
Stefano
S
Bonfanti
Annalisa
A
Brambilla
Stefania
S
Gale
David C
DC
Li
Lin
L
Miglietta
Daniela
D
Nicoli
Fabio
F
Prasanna
Ganesh A
GA
Ronchetti
Daniela
D
Vernier
William F
WF
Chong
Wesley K M
WK
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