2. Academic Validation
  3. Spirodiketopiperazine-based CCR5 antagonist: discovery of an antiretroviral drug candidate

Spirodiketopiperazine-based CCR5 antagonist: discovery of an antiretroviral drug candidate

  • Bioorg Med Chem Lett. 2011 Feb 15;21(4):1141-5. doi: 10.1016/j.bmcl.2010.12.109.
Rena Nishizawa 1,  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,  Hiroaki Mitsuya
Affiliations

Affiliation

  • 1 Medicinal Chemistry Research Laboratory, Ono Pharmaceutical Co., Ltd, Shimamoto, Mishima, Osaka 618-8585, Japan. [email protected]
PMID: 21256008 DOI: 10.1016/j.bmcl.2010.12.109
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.

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