Pfizer Corporation

Dsm N.v.

Bone Care International, Inc.

Kees Pouwer

Derek Lawrence Tickner

Clifford N Meltz

Ton Rene Vries

Marcus D Ewing

Subramanian Sam Guhan

R Mark Guinn

Karl K Ng

Bryan Li

Hans Wynberg

Hans Wijnberg

Jose Nieuwenhuijzen

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 (&#x2212;)-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)-(&#x2212;)-1,1'-binapthyl-2,2&#x2032;-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.

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

This invention relates to the enantiomers of 6-&lsqb;(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl&rsqb;-4-&lsqb;3-(3-hydroxy-3-methyl-but-1-ynyl)-phenyl&rsqb;-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 (&plus;)- or (&minus;)-6-&lsqb;(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl&rsqb;-4-&lsqb;3-(3-hydroxy-3-methyl-but-1-ynyl)-phenyl&rsqb;-1-methyl-1H-quinolin-2-one enantiomers from a mixture containing two enantiomers using continuous chromatography. The invention further relates to the L-(&plus;)-tartaric acid or (S)-(&minus;)-1,1&prime;-binapthyl-2,2&prime;-diyl hydrogenphosphate salts of (&plus;)-6-&lsqb;(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl&rsqb;-4-&lsqb;3-(3-hydroxy-3-methyl-but-1-ynyl)-phenyl&rsqb;-1-methyl-1H-quinolin-2-one.

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

The invention relates to 1,3-disubstituted-3-oxopropane-1-sulfonic acids and sulfonates and enantiomerically inriched forms thereof. The invention further relates to the use of these enantiomerically inriched compounds to resolve mixtures of enantiomers, in particular mixtures of enantiomers of amino-functionalized compounds.

3-oxopropane-1-sulphonic acids and sulphonates

The present invention provides a method for preparing a novel class of vitamin D compounds in which the C-25 or equivalent position has a double bond. In addition, the side chain is optionally extended by one or two methylene or methyne groups. The compounds prepared by the method of the present invention are of value as prodrugs for active 1&agr;, 24-dihydroxylated vitamin D compounds.

Method for making hydroxy-25-ene-vitamin D compounds

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Groningen, Netherlands

Kees Pouwer