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Updated: Jul 14, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
3-Hydroxy-1,5-dihydro-pyrrol-2-one derivatives as advanced inhibitors of HIV integrase
Takashi Kawasuji1, Masahiro Fuji, Tomokazu Yoshinaga
1Shionogi Research Laboratories, Shionogi & Company, Ltd, Sagisu, Fukushima-ku, Osaka 553-0002, Japan. kawasuji@shionogi.co.jp
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.
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