Beta-substituted beta-amino acids and analogs as chemotherapeutic agents and uses thereof

US10246406B2 · 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
• Gordon Ringold · Palo Alto, US

Key dates

• Filing date: May 22, 2018
• Grant date: Apr 2, 2019
• Expiry date: May 22, 2038

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07B2200/07
• 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.