title: Bis[(para-methoxy)benzyl] phosphonate prodrugs with improved stability and enhanced cell penetration.
abstract: A series of substituted bis[(para-methoxy)benzyl] (bisPMB) esters of 1-naphthalenemethylphosphonate (NMPA) were synthesized and evaluated as phosphonate prodrugs. BisPMB NMPA esters (4b and 4c) with significantly improved aqueous stability were identified that also resulted in increased intracellular levels of NMPA following prodrug incubation with primary rat hepatocytes.
authors: Department of Chemistry, Metabasis Therapeutics, Inc., 11119 North Torrey Pines Road, La Jolla, CA 92037, USA. dang@mbasis.com
authors: Qun
authors: Q
authors: Dang
authors: Yan
authors: Y
authors: Liu
authors: Robert M
authors: RM
authors: Rydzewski
authors: Brian S
authors: BS
authors: Brown
authors: Edward
authors: E
authors: Robinson
authors: Paul D
authors: PD
authors: van Poelje
authors: Timothy J
authors: TJ
authors: Colby
authors: Mark D
authors: MD
authors: Erion
mesh_terms: D000818:Animals; D004355:Drug Stability; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008956:Models, Chemical; D063065:Organophosphonates / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000138:chemical synthesis / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
chemical_list: D063065:Organophosphonates; D009943:Organophosphorus Compounds; D011355:Prodrugs; C522192:bis((para-methoxy)benzyl) phosphonate