title: Pyridopyrimidinone inhibitors of HIV-1 RNase H.
abstract: Using a structure based pharmacophore design, a weak inhibitor of RNase H, identified from a small library of two metal binding HIV-1 integrase inhibitors, was optimized for potency and physicochemical properties. This manuscript describes the SAR and in vivo DMPK for the pyridopyrimidinone class of inhibitors.
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States. Electronic address: emile.j.velthuisen@gsk.com.
authors.forename: Emile J
authors.initials: EJ
authors.lastname: Velthuisen
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Johns
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Gerondelis
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Ke
authors.initials: K
authors.lastname: Mou
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: John W
authors.initials: JW
authors.lastname: Seal
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Kendra E
authors.initials: KE
authors.lastname: Hightower
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Sonia R
authors.initials: SR
authors.lastname: Miranda
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Brown
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Leesnitzer
mesh_terms: D000818:Animals; D015497:HIV-1 / Q000201:enzymology*; D008297:Male; D011744:Pyrimidinones / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D054309:Ribonuclease H, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D054309:Ribonuclease H, Human Immunodeficiency Virus
keywords: AIDS; Endonuclease; HIV; Integrase; Reverse transcriptase; Two-metal binder