title: Recent progress in small molecule CCR5 antagonists as potential HIV-1 entry inhibitors.
abstract: Currently the long-term usage of traditional anti-HIV drugs, such as nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), eventually leads to the emergence of drug resistance and severe side effects. Thus it is imperative to design and develop more promising HIV-1 inhibitors to overcome these drawbacks. Fortunately, with the identification of some fascinating targets in the entry process of viral life cycle, HIV-1 entry inhibitors (EIs) with low cytotoxicity and mild side effects turned out as novel and effective anti-HIV agents. Especially, of these potent EIs, small molecule CCR5 antagonist maraviroc was approved by US FDA in 2007, which significantly increased the therapeutic options for the clinical treatment of HIV-infected patients. Subsequently, as promising anti-HIV drug candidates, kinds of small molecule CCR5 antagonists have been synthesized and evaluated in clinical trials. In this article, current progress in the development of novel small molecule CCR5 antagonists will be reviewed on the basis of their chemical structures with a special attention to their discovery stories. Simultaneously, binding mode analysis based on molecular modeling studies will also be introduced.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, PR China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D065100:CCR5 Receptor Antagonists; D002986:Clinical Trials as Topic; D015195:Drug Design; D024882:Drug Resistance, Viral; D023581:HIV Fusion Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D065100:CCR5 Receptor Antagonists; D023581:HIV Fusion Inhibitors