Combination cancer therapy with bis(thiohydrazide) amide compounds

US8017654B2 · kind B2 · utility

Assignee

• Synta Pharmaceuticals Corp. · US

Inventors

• Thomas A. Dahl · Guilford, US
• Matthew McLeod · Boston, US

Key dates

• Filing date: Apr 13, 2006
• Grant date: Sep 13, 2011
• Expiry date: Dec 13, 2026

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P35/04
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A method of treating a subject with cancer includes the step of co-administering to the subject over three to five weeks, a taxane in an amount of between about 243 μmol/m2 to 315 μmol/m2 (e.g., equivalent to paclitaxel in about 210-270 mg/m2); and a bis(thiohydrazide amide) in an amount between about 1473 μmol/m2 and about 1722 μmol/m2 (e.g., Compound (1) in about 590-690 mg/m2). The bis(thiohydrazide amide) is represented by Structural Formula (I), Y is a covalent bond or an optionally substituted straight chained hydrocarbyl group, or, Y, taken together with both >C=Z groups to which it is bonded, is an optionally substituted aromatic group. R1-R4 are independently —H, an optionally substituted aliphatic group, an optionally substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. R7-R8 are independently —H, an optionally substituted aliphatic group, or an optionally substituted aryl group. Z is O or S.