title: Hydroxamates: relationships between structure and plasma stability.
abstract: Hydroxamates are valuable tools for chemical biology as well as interesting leads for medicinal chemistry. Although many hydroxamates display nanomolar activities against metalloproteases, only three hydroxamates have reached the market, among which is the HDAC inhibitor vorinostat. Failures in development are generally attributed to lack of selectivity, toxicity, or poor stability. To help medicinal chemists with respect to plasma stability, we have performed the first and preliminary study on structure-plasma stability for hydroxamates. We define some structural rules to predict or improve the plasma stability in the preclinical stage.
authors.affiliation: INSERM U761 Biostructures and Drug Discovery, Univ Lille Nord de France, Lille F-59006, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Flipo
authors.forename: Julie
authors.initials: J
authors.lastname: Charton
authors.forename: Akila
authors.initials: A
authors.lastname: Hocine
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dassonneville
authors.forename: Benoit
authors.initials: B
authors.lastname: Deprez
authors.forename: Rebecca
authors.initials: R
authors.lastname: Deprez-Poulain
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D004950:Esterases / Q000097:blood; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D006877:Hydroxamic Acids / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry; D010949:Plasma; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D006877:Hydroxamic Acids; D011355:Prodrugs; D004950:Esterases