Botryllamides and method of inhibiting PGP in a mammal afflicted with cancer

US8470888B2 · kind B2 · utility

Assignee

• The United States of America, as represented by the Secretary, Department of Health and Human Services · US

Inventors

• Curtis J. Henrich · Rockville, US
• Heidi R. Bokesch · Frederick, US
• Laura K. Cartner · Middletown, US
• Richard W. Fuller · Fairfield, US
• Kirk R. Gustafson · Frederick, US
• Kentaro Takada · Yokohama, JP
• James B. McMahon · Frederick, US
• Susan E. Bates · Bethesda, US
• Robert W. Robey · Laurel, US
• Suneet Shukla · Rockville, US
• Suresh V. Ambudkar · Gaithersburg, US
• Michael Dean · Frederick, US

Key dates

• Filing date: Dec 29, 2008
• Grant date: Jun 25, 2013
• Expiry date: Sep 14, 2029

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D311/92
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Disclosed are methods of enhancing the chemotherapeutic treatment of tumor cells, reducing resistance of a cancer cell to a chemotherapeutic agent, a method of inhibiting ABCG2, Pgp, or MRP1 in a mammal afflicted with cancer, and a method of increasing the bioavailability of an ABCG2 substrate drug in a mammal. The methods comprise administering effective amounts of certain compounds to the mammal, for example, a compound of the formula (I): Formula (I), wherein R1, R2, R3, X1, X2, X3, a, and b are as described herein. Uses of these compounds in the preparation of a medicament are also disclosed. Also disclosed are compounds of formula (II), pharmaceutical compositions comprising such compounds and uses thereof.