CD4 mimics targeting the HIV entry mechanism and their hybrid molecules with a CXCR4 antagonist

  • Bioorg Med Chem Lett. 2010 Oct 1;20(19):5853-8. doi: 10.1016/j.bmcl.2010.07.106.
Tetsuo Narumi  1 ,  Chihiro Ochiai ,  Kazuhisa Yoshimura ,  Shigeyoshi Harada ,  Tomohiro Tanaka ,  Wataru Nomura ,  Hiroshi Arai ,  Taro Ozaki ,  Nami Ohashi ,  Shuzo Matsushita ,  Hirokazu Tamamura
Affiliations
  • 1. Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.
PMID: 20728351 DOI: 10.1016/j.bmcl.2010.07.106
Abstract

Small molecules behaving as CD4 mimics were previously reported as HIV-1 entry inhibitors that block the gp120-CD4 interaction and induce a conformational change in gp120, exposing its co-receptor-binding site. A structure-activity relationship (SAR) study of a series of CD4 mimic analogs was conducted to investigate the contribution from the piperidine moiety of CD4 mimic 1 to anti-HIV activity, cytotoxicity, and CD4 mimicry effects on conformational changes of gp120. In addition, several hybrid molecules based on conjugation of a CD4 mimic analog with a selective CXCR4 Antagonist were also synthesized and their utility evaluated.