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ID: ALA4422649

Journal: Bioorg Med Chem Lett

Title: Soluble-type small-molecule CD4 mimics as HIV entry inhibitors.

Authors: Kobayakawa T, Konno K, Ohashi N, Takahashi K, Masuda A, Yoshimura K, Harada S, Tamamura H.

Abstract: Several small molecule CD4 mimics have been reported previously as HIV-1 entry inhibitors, which block the interaction between the Phe43 cavity of HIV-1 gp120 and the host CD4. Known CD4 mimics such as NBD-556 possess significant anti-HIV activity but are less soluble in water, perhaps due to their hydrophobic aromatic ring-containing structures. Compounds with a pyridinyl group in place of the phenyl group in these molecules have been designed and synthesized in an attempt to increase the hydrophilicity. Some of these new CD4 mimics, containing a tetramethylpiperidine ring show significantly higher water solubility than NBD-556 and have high anti-HIV activity and synergistic anti-HIV activity with a neutralizing antibody. The CD4 mimic that has a cyclohexylpiperidine ring and a 6-fluoropyridin-3-yl ring has high anti-HIV activity and no significant cytotoxicity. The present results will be useful in the future design and development of novel soluble-type molecule CD4 mimics.

CiteXplore: 30665681

DOI: 10.1016/j.bmcl.2019.01.011