Wyeth

Arqule, Inc.

Dennis Martin Kubrak

Anthony Frank Kreft

Derek Cecil Cole

Joseph Raymond Stock

Lynn Resnick

David S Casebier

Kevin R Woller

Thomas Joseph Caggiano

Donna Mary Huryn

William Jay Moore

Koi Morris

Joan E Sabalski

Charles William Mann

Kristina Martha Kutterer

Joshua D Berkowitz

Madelene M Antane

Zheng Wang

Compounds useful for lowering beta amyloid levels are provided. The compounds have the structure of formula Ia: wherein, Ris lower alkyl, substituted lower alkyl, phenyl, substituted phenyl, benzyl, substituted benzyl, benzyloxy, substituted benzyloxy, or SOR; Ris phenyl, substituted phenyl, heterocycle, substituted heterocycle, alkyl, or substituted alkyl; Ris lower alkyl, substituted lower alkyl, CF, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, or cycloalkyl; Ris hydrogen, lower alkyl, or substituted lower alkyl; Ris phenyl, substituted phenyl, heterocycle, substituted heterocycle, thiophene, or substituted thiophene; Ris hydrogen, lower alkyl, substituted lower alkyl, CF, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, cycloalkyl, or substituted cycloalkyl; W, X and Y are independently CRor N; and Ris hydrogen, halogen, lower alkyl, or substituted lower alkyl.

Heterocyclic sulfonamide inhibitors of beta amyloid production containing an azole

Compounds of Formula I,  wherein R-Rare defined herein are provided, together with pharmaceutically acceptable salts, hydrates, metabolites, and/or prodrugs thereof. Uses of these compounds for inhibiting beta amyloid production and for the prevention and treatment of Alzheimer's Disease and Down's syndrome are also described.

Substituted phenylsulfonamide inhibitors of beta amyloid production

Compounds useful for lowering beta amyloid levels are provided. The compounds have the structure of formula Ia: 

A process is provided for preparing chirally pure S-enantiomers of &agr;-amino acids comprising the steps of: a) preparing an organometallic reagent from an alkyl halide of the formula (R) CH(CH ) CH X; b) adding the organometallic reagent to carbon dioxide to afford a carboxylic acid; c) activating the carboxylic acid with an acid chloride, phosphorus trichloride, acid anhydride, or thionyl chloride in the presence of a tertiary amine base; d) reacting the product of step c) with an alkali metal salt of S-4-benzyl-2-oxazolidinone; e) treating the product of step d) with a strong non-nucleophilic base to form an enolate anion; f) trapping the enolate anion with 2,4,6-triisopropylbenzenesulfonyl azide to afford an oxazolidinone azide; g) hydrolyzing the oxazolidinone azide with an aqueous base to afford an &agr;-azido acid; h) reducing the &agr;-azido acid to the &agr;-amino acid; and i) recrystallizing the &agr;-amino acid to the chirally pure &agr;-amino acid. A process is also provided for preparing chirally pure S-enantiomers of &bgr;-amino alcohols further comprising the steps of reducing the crude &agr;-amino acid to the &bgr;-amino alcohol and recrystallizing the &bgr;-amino alcohol to the chirally pure &bgr;-amino alcohol. A process is further provided for preparing chirally pure S enantiomers of N-sulfonyl &bgr;-amino alcohols further comprising the steps of sulfonylating the &bgr;-amino alcohol with 5-chloro-thiophene-2-sulfonyl halide; and recrystallizing to afford the chirally pure N-sulfonyl &bgr;-amino alcohols.

Process for the synthesis of chirally pure beta-amino-alcohols

Growing community of inventors

Philadelphia, PA, United States of America

Dennis Martin Kubrak