title: Antibacterial barbituric acid analogues inspired from natural 3-acyltetramic acids; synthesis, tautomerism and structure and physicochemical property-antibacterial activity relationships.
abstract: The synthesis, tautomerism and antibacterial activity of novel barbiturates is reported. In particular, 3-acyl and 3-carboxamidobarbiturates exhibited antibacterial activity, against susceptible and some resistant Gram-positive strains of particular interest is that these systems possess amenable molecular weight, rotatable bonds and number of proton-donors/acceptors for drug design as well as less lipophilic character, with physicochemical properties and ionic states that are similar to current antibiotic agents for oral and injectable use. Unfortunately, the reduction of plasma protein affinity by the barbituric core is not sufficient to achieve activity in vivo. Further optimization to reduce plasma protein affinity and/or elevate antibiotic potency is therefore required, but we believe that these systems offer unusual opportunities for antibiotic drug discovery.
authors.affiliation: Chemistry Research Laboratory, Mansfield Rd, University of Oxford, OX1 3TA, UK. ycjchem@gmail.com.
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Jeong
authors.affiliation: Chemistry Research Laboratory, Mansfield Rd, University of Oxford, OX1 3TA, UK. mark.moloney@chem.ox.ac.uk.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Moloney
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001463:Barbiturates / Q000737:chemistry* / Q000494:pharmacology*; D055598:Chemical Phenomena; D055808:Drug Discovery; D005663:Furans / Q000737:chemistry* / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001463:Barbiturates; D005663:Furans; C066006:3-acetyltetramic acid; C032232:barbituric acid