title: Design and structure-activity relationships of potent and selective inhibitors of undecaprenyl pyrophosphate synthase (UPPS): tetramic, tetronic acids and dihydropyridin-2-ones.
abstract: Based on a pharmacophore hypothesis substituted tetramic and tetronic acid 3-carboxamides as well as dihydropyridin-2-one-3-carboxamides were investigated as inhibitors of undecaprenyl pyrophosphate synthase (UPPS) for use as novel antimicrobial agents. Synthesis and structure-activity relationship patterns for this class of compounds are discussed. Selectivity data and antibacterial activities for selected compounds are provided.
authors.affiliation: Novartis Institutes for BioMedical Research, Inc., 250 Massachusetts Avenue, Cambridge, MA 02139, USA. stefanpeukert@yahoo.com
authors.forename: Stefan
authors.initials: S
authors.lastname: Peukert
authors.forename: Yingchuan
authors.initials: Y
authors.lastname: Sun
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Brian
authors.initials: B
authors.lastname: Hurley
authors.forename: Mike
authors.initials: M
authors.lastname: Sabio
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Shen
authors.forename: Christen
authors.initials: C
authors.lastname: Gray
authors.forename: JoAnn
authors.initials: J
authors.lastname: Dzink-Fox
authors.forename: Jianshi
authors.initials: J
authors.lastname: Tao
authors.forename: Regina
authors.initials: R
authors.lastname: Cebula
authors.forename: Sompong
authors.initials: S
authors.lastname: Wattanasin
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology*; D003500:Cyclization; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D005663:Furans / Q000138:chemical synthesis / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D011487:Protein Conformation; D011760:Pyrrolidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000254:growth & development; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D005663:Furans; D011106:Polyisoprenyl Phosphates; D011760:Pyrrolidinones; D012717:Sesquiterpenes; C009435:tetramic acid; C004808:farnesyl pyrophosphate; D019883:Alkyl and Aryl Transferases; C023266:undecaprenyl pyrophosphate synthetase; C003422:tetronic acid