title: Synthesis, hydrolyses and dermal delivery of N-alkyl-N-alkyloxycarbonylaminomethyl (NANAOCAM) derivatives of phenol, imide and thiol containing drugs.
abstract: Synthesis, characterization and hydrolysis in aqueous buffers of novel N-alkyl-N-alkyloxycarbonylaminomethyl (NANAOCAM) derivatives of substituted phenols, theophylline (Th) and 6-mercaptopurine (6MP) were carried out. The mechanism of hydrolysis was further investigated by synthesis, characterization and hydrolysis of N-aryl-N-alkyloxycarbonylaminomethyl (NArNAOCAM) derivatives of phenols. The hydrolysis follows pseudounimolecular first order kinetics and operates by way of an S(N)1-type mechanism. Topical delivery of selected derivatives of acetaminophen (APAP), Th and 6MP was examined in in vitro diffusion cell experiments from IPM across hairless mice skins. The prodrug of APAP and 6MP increased permeation across the skin by about 2- and 4-fold, respectively, compared to the parent drug. NANAOCAM promoieties can act as novel prodrug derivatives of phenol, imide and thiol containing drugs for enhancing topical absorption.
authors.affiliation: Department of Medicinal Chemistry, University of Florida, Gainesville, 32610, USA.
authors.forename: Susruta
authors.initials: S
authors.lastname: Majumdar
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Sloan
mesh_terms: D000279:Administration, Cutaneous; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007094:Imides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D007094:Imides; D010636:Phenols; D011355:Prodrugs; D013438:Sulfhydryl Compounds