1499-54-3Relevant academic research and scientific papers
In silico design of HDAC6 inhibitors with neuroprotective effects
Bello, Martiniano,de Pedro, Nuria,Correa-Basurto, José,Gómez-Vidal, José Antonio,Rosales-Hernández, Martha Cecilia,Sixto-López, Yudibeth
, (2021/11/24)
HDAC6 has emerged as a molecular target to treat neurodegenerative disorders, due to its participation in protein aggregate degradation, oxidative stress process, mitochondrial transport, and axonal transport. Thus, in this work we have designed a set of
Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox
Hermant, Paul,Bosc, Damien,Piveteau, Catherine,Gealageas, Ronan,Lam, Baovy,Ronco, Cyril,Roignant, Matthieu,Tolojanahary, Hasina,Jean, Ludovic,Renard, Pierre-Yves,Lemdani, Mohamed,Bourotte, Marilyne,Herledan, Adrien,Bedart, Corentin,Biela, Alexandre,Leroux, Florence,Deprez, Benoit,Deprez-Poulain, Rebecca
, p. 9067 - 9089 (2017/11/14)
Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models.
A convenient procedure for the solid-phase synthesis of hydroxamic acids on PEGA resins
Nandurkar, Nitin S.,Petersen, Rico,Qvortrup, Katrine,Komnatnyy, Vitaly V.,Taveras, Kennedy M.,Le Quement, Sebastian T.,Frauenlob, Robin,Givskov, Michael,Nielsen, Thomas E.
supporting information; experimental part, p. 7121 - 7124 (2012/01/14)
An efficient method for the solid-phase synthesis of hydroxamic acids is described. The method comprises the nucleophilic displacement of esters immobilized on PEGA resins with hydroxylamine/sodium hydroxide in isopropanol. The hydroxyaminolysis protocol
