Thermally stable trimetrexates and processes for producing the same

US6017922A · kind A · utility

Assignee

• U.S. Bioscience, Inc. · US

Inventors

• Martin Stogniew · Blue Bell, US
• Ingomar Grafe · Nürnberg, DE
• Johann Peter Morsdorf · Langenzenn, DE

Key dates

• Filing date: May 18, 1998
• Grant date: Jan 25, 2000
• Expiry date: May 18, 2018

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P35/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present invention provides for thermally stable forms of 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl] quinazoline, or trimetrexate. A crystalline 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl] quinazoline monohydrate, or trimetrexate monohydrate, belonging to the space group P1(#2) and having a triclinic cell with dimensions of about a=7.699 .ANG., b=9.606 .ANG. and c=13.012 .ANG. is disclosed. A novel Schiff base compound, 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyphenylimino)-methinyl]quinazoline , is also disclosed. The present invention further provides novel methods of producing stable trimetrexate free base compounds, including crystalline trimetrexate monohydrate. The crystalline monohydrate form provides increased stability over the anhydrous form.