Smithkline Corporation

Smithkline Beecham Corporation

Smithkline Beckman Corporation

Ivan Lantos

David T Hill

Blaine M Sutton

Paul E Bender

Wilford L Mendelson

Robert John Mills

Paul G Gassman

Michael Anthony McGuire

Lendon N Pridgen

William Morrow Clark

Joseph Robert Flisak

Lendon Norwood Pridgen

Ann Marie Tickner

Herbert B Winicov

John G Gleason

Don Edgar Griswold

Henry M Sarau

Nabil Hanna

Susan C Shilcrat

Kazys A Razgaitis

Invented is an improved process for preparing aromatic ring-fused cyclopentane derivatives. Preferred compounds prepared by this invention are indane carboxylates and cyclopentanopyridine derivatives. The most preferred compounds prepared by this invention are (&plus;)(1S, 2R, 3S)-3-&lsqb;2-(2-hydroxyeth-1-yloxy)-4-methoxyphenyl&rsqb;-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indane-2-carboxylic acid and pharmaceutically acceptable salts thereof and (&plus;)(1S, 2R, 3S)-3-(2-carboxymethoxy-4-methoxyphenyl)-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indane-2-carboxylic acid and pharmaceutically acceptable salts thereof. Also invented are novel intermediates useful in preparing these compounds.

process of making 3-phenyl-1-methylenedioxyphenyl-indane-2-carboxylic acid derivatives

3-phenyl-1-methylenedioxyphenyl-indane-2-carboxylic acid derivatives

This invention relates to a process for preparing epoxy esters, and intermediates prepared by this process, in particular, to a process which produces non-racemic epoxy esters which are of use as intermediates in the preparation of pharmaceutical compounds.

Intermediates for preparing epoxy esters

A method of inhibiting the 5-lipoxygenase pathway in an animal in need thereof which comprises administering an effective, 5-lipoxygenase pathway inhibiting amount of a diaryl- substituted imidazole fused to a thiazole pyrrolidine, thiazide or piperidine ring to such animal.

Inhibition of the 5-lipoxygenase pathway

Process for preparation of epoxy esters and intermediates prepared

6-Aryl-2,3-dihydroimidazo[2,1-b]thiazoles and corresponding thiazines act as nucleophiles, either directly or in the form of Grignard reagents, with N-acylpyridinium salts to produce new 6-aryl-5-(N-acyl-1,4-dihydro-4-pyridyl)-2,3-dihydroimidazo-[2,1-b]thiazole s and corresponding thiazines. These are oxidized to give the corresponding pyridyl-substituted imidazo[2,1-b]thiazoles and thiazines, which are active as inhibitors of the 5-lipoxygenase pathway of arachidonic acid metabolism.

Compounds for preparing 6-phenyl-2,3-dihydroimidazo[2,1-b]-thiazoles and

1.4-dihydro-4-pyridyl-substituted imidazo (2,1-b) thiazoles and the

A new synthesis of auranofin comprising reacting 2,3,4,6-tetra-O-acetyl-.alpha.-D-glucopyranosyl bromide with a S-(triethylphosphineaurous)thiouronium salt.

Method for preparing auranofin

The compounds are 5/6-pyridyl-phenyl-2,3-dihydroimidazo[2,1-b]thiazoles which have utility as intermediates and/or as having antiarthritic activity. A preferred group of compounds is 5-(4-pyridyl)-6-(4-substituted phenyl)-2,3-dihydroimidazo[2,1-b]thiazoles which have significant anti-arthritic activity.

Pyridyl substituted 2,3-dihydroimidazo[2,1-b]thiazoles

The S-gold salt of 2,3,4,6-tetra-O-acetyl-1-thio-.beta.-D-glucopyranose reacts with triethylphosphine in an organic solvent to produce auranofin.

Process and intermediate for preparing auranofin

A new synthesis of auranofin comprising reacting 2,3,4,6-tetra-O-acetyl-.alpha.-D-glucopyranosyl bromide with triethylphosphinegold(I) chloride and sodium or potassiumsulfide. Auranofin is an antiarthritic pharmaceutical compound. Auranofin is an orally active therapeutic agent which is useful in man as an antiarthritic.

Bis(triethylphosphine)gold salts are advantageous agents for preparing auranofin.

Auranofin is prepared by reacting 1-.beta.-D-thio-2,3,4,6-tetra-O-acetylglucose with a triethylphosphine gold mercaptide.

Process for preparing auranofin

Auranofin is prepared by direct O-acetylation of S-triethylphosphinegold 1-thio-.beta.-D-glucopyranoside.

Preparation of auranofin by O-acetylation

Auranofin and its congeners are prepared by the reaction of a S-substituted 2,3,4,6-tetra-O-acetyl-1-thio-.beta.-D-glucopyranose with a tertiary phosphine gold ester or sulfide.

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Blackwood, NJ, United States of America

Ivan Lantos