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

US9937139B2 · 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: May 15, 2017
• Grant date: Apr 10, 2018
• Expiry date: May 15, 2037

Classification

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

Abstract

β-Substituted γ-amino acids, β-substituted γ-amino acid derivatives, and β-substituted γ-amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The β-substituted γ-amino acid derivatives and β-substituted γ-amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates, capable of passing through the blood-brain barrier, and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the β-substituted γ-amino acid derivatives and β-substituted γ-amino acid analogs and (bio)isosteres and methods of using the compounds for treating tumors are also disclosed. The β-substituted γ-amino acid derivatives and β-substituted γ-amino acid analogs and (bio)isosteres exhibit an improved selectivity toward tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The β-substituted γ-amino acid derivatives and β-substituted γ-amino acid analogs and (bio)isosteres exhibit an increased efficacy on a variety of tumor types.