title: Design, synthesis and biological evaluation of potent NAD+-dependent DNA ligase inhibitors as potential antibacterial agents. Part 2: 4-amino-pyrido[2,3-d]pyrimidin-5(8H)-ones.
abstract: A series of 4-amino-pyrido[2,3-d]pyrimidin-5(8H)-ones were designed and synthesized as a novel class of inhibitors of NAD(+)-dependent DNA ligase that possess potency against Gram-positive bacteria.
authors.affiliation: Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA 02139, United States. tiansheng_wang@vrtx.com
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Wang
authors.forename: Leonard
authors.initials: L
authors.lastname: Duncan
authors.forename: Wenxin
authors.initials: W
authors.lastname: Gu
authors.forename: Hardwin
authors.initials: H
authors.lastname: O'Dowd
authors.forename: Yunyi
authors.initials: Y
authors.lastname: Wei
authors.forename: Emanuele
authors.initials: E
authors.lastname: Perola
authors.forename: Jonathan
authors.initials: J
authors.lastname: Parsons
authors.forename: Christian H
authors.initials: CH
authors.lastname: Gross
authors.forename: Cameron Stuver
authors.initials: CS
authors.lastname: Moody
authors.forename: S J Ryan
authors.initials: SJ
authors.lastname: Arends
authors.forename: Paul S
authors.initials: PS
authors.lastname: Charifson
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009243:NAD / Q000378:metabolism; D011744:Pyrimidinones / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D011744:Pyrimidinones; D009243:NAD; D011088:DNA Ligases; D000072481:DNA Ligase ATP