A platform for designing HIV integrase inhibitors. Part 1: 2-hydroxy-3-heteroaryl acrylic acid derivatives as novel HIV integrase inhibitor and modeling of hydrophilic and hydrophobic pharmacophores.
We present a novel series of HIV integrase inhibitors, showing IC(50)s ranging from 0.01 to over 370microM in an enzymatic assay. Furthermore, pharmacophore modeling study for the inhibitors was carried out to elucidate the structure-activity relationships. Finally, we found a 3D-pharmacophore model, which is composed of a hydrophilic and a hydrophobic domain, providing valuable information for designing other novel types of integrase inhibitors.
Kawasuji
Takashi
T
Shionogi Research Laboratories, Shionogi & Company, Ltd, Sagisu, Fukushima-ku, Osaka 553-0002, Japan. takashi.kawasuji@shionogi.co.jp
Yoshinaga
Tomokazu
T
Sato
Akihiko
A
Yodo
Mitsuaki
M
Fujiwara
Tamio
T
Kiyama
Ryuichi
R
D000179:Acrylates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D015195:Drug Design; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000179:Acrylates; D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase