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Synthesis of novel nitric oxide (NO)-releasing esters of timolol |
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| Authors: | Valerio Chiroli Minerva R Batugo Stefano Biondi Annalisa Bonfanti Stefania Brambilla David C Gale Lin Li Daniela Miglietta Fabio Nicoli Ganesh A Prasanna Daniela Ronchetti William F Vernier Wesley KM Chong |
| Institution: | 1. NicOx Research Institute, Via Ariosto 21, 20091 Bresso (Milan), Italy;2. Pfizer Global Research and Development-La Jolla, 10770 Science Center Drive, San Diego, CA 92121, USA |
| Abstract: | 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. |
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