ENANTIOMERS OF 6-[(4-CHLORO-PHENYL)-HYDROXY-(3-METHYL-3H-IMIDAZOL-4-YL)-METHYL]-4-[3-(3-HYDROXY-3-METHYL-BUT-1-YNYL)-PHENYL]-1-METHYL-1H-QUINOLIN-2-ONE AND SALTS THEREOF, USEFUL IN THE TREATMENT OF CANCER

US6740757B2 · kind B2 · utility

Assignee

• PFIZER INC. · US

Inventors

• R. Mark Guinn · Mystic, US
• Subramanian Sam Guhan · Niantic, US
• Karl Ng · East Greenwich, US
• Derek Tickner · Waterford, US
• Marcus Ewing · Colchester, US
• Clifford N. Meltz · Niantic, US
• Bryan Li · East Lyme, US
• Kees Pouwer · Groningen, NL

Key dates

• Filing date: Aug 27, 2002
• Grant date: May 25, 2004
• Expiry date: Aug 27, 2022

Classification

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

Abstract

This invention relates to the enantiomers of 6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but-1-ynyl)-phenyl]-1-methyl-1H-quinolin-2-one, prodrugs thereof, and pharmaceutically acceptable salts and solvates of said compounds and said prodrugs, that are useful in the treatment of hyperproliferative diseases, such as cancers, in mammals. The invention also relates to processes for the production of enantiomerically pure or optically enriched (+)- or (−)-6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but-1-ynyl)-phenyl]-1-methyl-1H-quinolin-2-one enantiomers from a mixture containing two enantiomers using continuous chromatography. The invention further relates to the L-(+)-tartaric acid or (S)-(−)-1,1′-binapthyl-2,2′-diyl hydrogenphosphate salts of (+)-6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but-1-ynyl)-phenyl]-1-methyl-1H-quinolin-2-one.