CD4-mimetic inhibitors of HIV-1 entry and methods of use thereof

US9403763B2 · kind B2 · utility

Inventors

• Joseph Sodroski · Medford, US
• Judith M. LaLonde · Havertown, US
• Amos B. Smith, III · Yeadon, US
• Peter Kwong · Washington, US
• Young Do Kwon · Bethesda, US
• David M. Jones · Ramsey, US
• Alexander W. Sun · Eugene, US
• Joel R. Courter · Glen Mills, US
• Takahiro Soeta · Ishikawa, JP
• Toyoharu Kobayashi · Tokyo, JP
• Amy M. Princiotto · Attleboro, US
• Xueling Wu · Potomac, US
• John Mascola · Rockville, US
• Arne Schon · Baltimore, US
• Ernesto Freire · Baltimore, US
• Navid Madani · Newton, US
• Matthew Le-Khac · Brooklyn, US
• Wayne A. Hendrickson · Dobbs Ferry, US
• Jongwoo Park · Daejeon, KR

Key dates

• Filing date: Dec 14, 2012
• Grant date: Aug 2, 2016
• Expiry date: Dec 14, 2032

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07C2602/08
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Described herein are small-molecule mimics of CD4, which both enter the Phe43 cavity and target Asp368 of gp120, the HIV-1 envelope protein. Also described herein are methods of using these compounds to inhibit the transmission or progression of HIV infection. These compounds exhibit antiviral potency greater than that of a known antiviral, NBD-556, with 100% breadth against clade B and C viruses. Importantly, the compounds do not activate HIV infection of CD4-negative, CCR5-positive cells, in contrast to NBD-556.