Pfizer Corporation

Glaxo Wellcome Inc.

Marcus Brackeen

Harry R Howard, Jr

Timothy Mark Willson

Brad Richard Henke

Istvan Kaldor

Robert Anthony Mook

David Norman Deaton

Elizabeth Ellen Sugg

Milana Dezube

Jon Loren Collins

Grady Evan Boswell

Matthew J Sharp

Christopher Joseph Aquino

Peter W Jeffs

Gavin Charles Hirst

John Mark O'Callaghan

Tanya Momtahen

Jeffrey Edmond Cobb

Edward Martin Suh

Greg Alan Erickson

A compound having formula (I), wherein A is selected from the group consisting of: (i) phenyl, wherein said phenyl is optionally substituted by one or more halogen atoms, C,alkyl, C,alkoxy, C,fluoroalkoxy, nitrile, or &mdash;NR,R,where R,and R,are independently hydrogen or C,alkyl; (ii) a 5- or 6-membered hetrocyclic group containing at least one heteroatom selected from oxygen, nitrogen and sulfur; and (iii) a fused bicyclic ring (a), wherein ring C represents a heterocyclic group as defined in point (ii) above, which bicyclic ring is attached to group B via a ring atom of ring C; B is selected from the group consisting of: (iv) C,alkylene; (v) &mdash;MC,alkylene or C,alkyleneMC,alkylene, wherein M is O, S, or &mdash;NR,wherein R,represents hydrogen or C,alkyl; (vi) a 5- or 6-membered heterocyclic group containing at least one nitrogen heteroatom and optionally at least one further heteroatom selected from oxygen, nitrogen and sulfur and optionally substituted by C,alkyl; and (vii) Het-C,alkylene, wherein Het represents a heterocyclic group as defined in point (vi) above; Alk represents C,alkylene; R,represents hydrogen or C,alkyl; Z is selected from the group consisting of: (viii) &mdash;(C,alkylene) phenyl, which phenyl is optionally substituted by one or more halogen atoms; and (ix) &mdash;NR,R,, wherein R,represents hydrogen or C,alkyl, and R,represents &mdash;Y&mdash;(C&boxH;O)&mdash;T&mdash;R,, or &mdash;Y&mdash;(CH(OH))&mdash;T&mdash;R,.

Substituted 4-hydroxy-phenylalcanoic acid derivatives with agonist activity to PPAR-gamma

CCK or gastrin modulating benzo �b!�1,4! diazepines derivatives

A novel three-step process for resolving a racemic spiro-hydantoin compound into its optical antipodes is disclosed, which involves (1) reacting said racemic compound with an optically-active asymmetric isocyanate of the formula RNCO, wherein R is (S)- or (R)-1-phenylethyl or (S)-or (R)-1-(1-naphthyl)ethyl, to form the corresponding diastereomeric ureido compound; (2) separating the resulting diastereomeric mixture into its component parts, and (3) thereafter converting the separated ureido diasteromers obtained in step (b) to the corresponding asymmetric hydantoin compounds by treatment with an alkali metal lower alkoxide (C.sub.1 -C.sub.4), followed by acidification, whereupon the desired optical isomer is obtained. The final products so obtained, such as (4S)-(+)-6-fluoro-2,3-dihydro-spiro-[4H-1-benzopyran-4,4'-imidazolidine]-2 ',5'-dione(sorbinil) and (5'S)-3'-chloro-5', 6',7',8'-tetrahydro-spiro[imidazolidine-4,5'-quinoline]-2,5-dione, are known to be useful in preventing or alleviating certain chronic diabetic complications. The aforementioned diastereomeric ureido intermediates are novel compounds.

Intermediates in a resolution process for racemic spiro hydantoins

A novel three-step process for resolving a racemic spiro-hydantoin compound into its optical antipodes is disclosed, which involves (1) reacting said racemic compound with an optically-active asymmetric isocyanate of the formula RNCO, wherein R is (S)- or (R)-1-phenylethyl or (S) or (R)-1-(1-naphthyl)ethyl, to form the corresponding diastereomeric uredio compound; (2) separating the resulting diastereomeric mixture into its component parts, and (3) thereafter converting the separated ureido diastereomers obtained in step (b) to the corresponding asymmetric hydantoin compounds by treatment with an alkali metal lower alkoxide (C.sub.1 -C.sub.4), followed by acidification, whereupon the desired optical isomer is obtained. The final products so obtained, such as (4S)-(+)-6-fluoro-2,3-dihydro-spiro[4H-1-benzopyran-4,4'-imidazolidine]-2' , 5'-dione (sorbinil) and (5'S)-3'-chloro-5', 6', 7', 8'-tetra-hydro-spiro[imidazolidine-4,5'-quinoline]-2,5-dione, are known to be useful in preventing or alleviating certain chronic diabetic complications. The aforementioned diastereomeric uredio intermediates are novel compounds.

Novel resolution process for racemic spiro-hydantoins

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Durham, NC, United States of America

Marcus Brackeen