title: Structure-activity relationships of 3-aminoquinazolinediones, a new class of bacterial type-2 topoisomerase (DNA gyrase and topo IV) inhibitors.
abstract: A series of 3-aminoquinazolinediones was synthesized and evaluated for its antibacterial and DNA gyrase activity. The SAR around the quinazolinedione core was explored and the optimal substitutions were combined to give two compounds, 2r and 2s, with exceptional enzyme potency (IC50 = 0.2 microM) and activity against gram-positive organisms (MIC's = 0.015-0.06 microg/mL).
authors.affiliation: Department of Chemistry, Pfizer Global Research and Development, Ann Arbor Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. tuan.tran@pfizer.com
authors.forename: Tuan P
authors.initials: TP
authors.lastname: Tran
authors.forename: Edmund L
authors.initials: EL
authors.lastname: Ellsworth
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Sanchez
authors.forename: Brian M
authors.initials: BM
authors.lastname: Watson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Stier
authors.forename: H D Hollis
authors.initials: HD
authors.lastname: Showalter
authors.forename: John M
authors.initials: JM
authors.lastname: Domagala
authors.forename: Martin A
authors.initials: MA
authors.lastname: Shapiro
authors.forename: E Themis
authors.initials: ET
authors.lastname: Joannides
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gracheck
authors.forename: Dai Q
authors.initials: DQ
authors.lastname: Nguyen
authors.forename: Paul
authors.initials: P
authors.lastname: Bird
authors.forename: Judy
authors.initials: J
authors.lastname: Yip
authors.forename: Anurag
authors.initials: A
authors.lastname: Sharadendu
authors.forename: Chan
authors.initials: C
authors.lastname: Ha
authors.forename: Saeed
authors.initials: S
authors.lastname: Ramezani
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Wu
authors.forename: Rajeshwar
authors.initials: R
authors.lastname: Singh
mesh_terms: D000588:Amines / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D027081:DNA Gyrase; D006094:Gram-Positive Bacteria / Q000187:drug effects; D020128:Inhibitory Concentration 50; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D000588:Amines; D000900:Anti-Bacterial Agents; D052999:Quinazolinones; D059005:Topoisomerase II Inhibitors; D027081:DNA Gyrase