title: 3-Hydroxy-1,5-dihydro-pyrrol-2-one derivatives as advanced inhibitors of HIV integrase.
abstract: The two-metal binding model we previously reported as an inhibition mechanism of HIV integrase (HIV IN) produced a new direction in modification of 2-hydroxy-3-heteroaryl acrylic acid inhibitors (HHAAs). Here we present a novel series of HIV IN inhibitors having a 3-hydroxy-1,5-dihydro-pyrrol-2-one moiety (HDPO) as an advanced analog of HHAAs. This cyclic modification of the chelating region of HHAA produces a favorable configuration to coordinate two-metal ions in HIV IN, which consequently gave improvements in not only enzymatic assay but also antiviral cell based assay in many cases.
authors.affiliation: Shionogi Research Laboratories, Shionogi & Company, Ltd, Sagisu, Fukushima-ku, Osaka 553-0002, Japan. kawasuji@shionogi.co.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawasuji
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fuji
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yoshinaga
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sato
authors.forename: Tamio
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Kiyama
mesh_terms: D000577:Amides / Q000737:chemistry; D006678:HIV / Q000187:drug effects; D019427:HIV Integrase / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C522703:3-hydroxy-1,5-dihydro-pyrrol-2-one; D000577:Amides; D019428:HIV Integrase Inhibitors; D011758:Pyrroles; D019427:HIV Integrase; D009584:Nitrogen