Design and structure-activity relationships of potent and selective inhibitors of undecaprenyl pyrophosphate synthase (UPPS): tetramic, tetronic acids and dihydropyridin-2-ones.
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.
Peukert
Stefan
S
Novartis Institutes for BioMedical Research, Inc., 250 Massachusetts Avenue, Cambridge, MA 02139, USA. stefanpeukert@yahoo.com
Sun
Yingchuan
Y
Zhang
Rui
R
Hurley
Brian
B
Sabio
Mike
M
Shen
Xiaoyu
X
Gray
Christen
C
Dzink-Fox
JoAnn
J
Tao
Jianshi
J
Cebula
Regina
R
Wattanasin
Sompong
S
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
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