β-substituted β-amino acids and analogs as chemotherapeutic agents

US9394237B2 · kind B2 · utility

Assignee

• QUADRIGA BIOSCIENCES, INC. · US

Inventors

• Bernd Jandeleit · Menlo Park, US
• Wolf-Nicolas Fischer · Sunnyvale, US
• Kerry J. Koller · San Francisco, US

Key dates

• Filing date: Feb 3, 2015
• Grant date: Jul 19, 2016
• Expiry date: Feb 3, 2035

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07F9/4816
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

β-Substituted β-amino acids, β-substituted β-amino acid derivatives, and β-substituted β-amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and methods of using the compounds for treating cancer are also disclosed. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs exhibit selective uptake in tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and (bio)isosteres exhibit cytotoxicity toward several tumor types.