| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1362179 | Bioorganic & Medicinal Chemistry Letters | 2011 | 5 Pages |
Abstract
Following the discovery that hydroxylated derivative 3 (Fig. 1) was one of the oxidative metabolites of the original lead 1, it was found that hydroxylated compound 4 possesses higher in vitro anti-HIV potency than the corresponding non-hydroxylated compound 2. Structural hybridation of 4 with the orally available analog 5 resulted in another orally-available spirodiketopiperazine CCR5 antagonist 6a that possesses more favorable pharmaceutical profile for use as a drug candidate.
Graphical abstractMolecular design of a new orally-available CCR5 antagonist.Figure optionsDownload full-size imageDownload as PowerPoint slide
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Authors
Rena Nishizawa, Toshihiko Nishiyama, Katsuya Hisaichi, Chiaki Minamoto, Naoki Matsunaga, Yoshikazu Takaoka, Hisao Nakai, Stephen Jenkinson, Wieslaw M. Kazmierski, Hideaki Tada, Kenji Sagawa, Shiro Shibayama, Daikichi Fukushima, Kenji Maeda,