Warner-lambert Company

Charles J Stankovic

John S Kiely

Mel C Schroeder

Michael R Pavia

Sheila H DeWitt

Kimberly Suzanne Para

Bruce D Roth

John C Hodges

Walter H Moos

Mark Stephen Plummer

Donna Reynolds Cody

Aurash B Shahripour

Bernd Janssen

Jay Bradford Fell

Alan Robert Saltiel

Elizabeth Ann Lunney

Sheryl Jeanne Hays

Tomi Sawyer

William Glen Harter

Josyula Venkata Prasad

Michael Connolly

Melean Visnick

Steven Ware

Paul Galatsis

James Knobelsdorf

Michael Kell

Juswinder Singh

Beth Lunney

The present invention provides indoles of Formula I: wherein Rand Rhave any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cardiovascular diseases, and cancers. Also provided are pharmaceutical compositions comprising one or more compounds of Formula I.

3-substituted indoles and derivatives thereof as therapeutic agents

The novel arylsulfonamide ether compounds, pharmaceutical compositions and uses thereof as inhibitors of interleukin-1&#x3b2; converting enzyme and other cysteine proteases in the ICE family are described. In one embodiment, the compound is described by the generalized structure:and pharmaceutically acceptable salts, esters, amides, and prodrugs thereof. In addition, methods of treating stroke, inflammatory diseases, septic shock, repurfusion injury, Alzheimer's disease, and shigellosis, using a compound of the invention or a pharmaceutical composition thereof, are described.

Arylsulfonamide ethers, and methods of use thereof

Compounds, compositions and methods for inhibiting the binding of

An apparatus and method which provides a suitable location for multiple, simultaneous synthesis of compounds. The apparatus consists of: a reservoir block having a plurality of wells; a plurality of reaction tubes, usually gas dispersion tubes, having filters on their lower ends; a holder block, having a plurality of apertures; and a manifold, which may have ports to allow introduction/maintenance of a controlled environment. The manifold top wall has apertures and a detachable plate with identical apertures. The apparatus is constructed from materials which will accommodate heating, cooling, agitation, or corrosive reagents. Gaskets are placed between the components. Rods or clamps are provided for fastening the components together. Apparatus operation involves placing the filters on the lower ends of the reaction tubes in the reservoir block wells, and the upper ends passing through the holder block apertures and into the manifold. The apparatus provides in excess of 1 mg of each product with structural knowledge and control over each compound. The apparatus can be adapted to manual, semiautomatic or fully automatic performance. Using the apparatus a series of building blocks are covalently attached to a solid support. These building blocks are then modified by covalently adding additional different building blocks or chemically modifying some existing functionality until the penultimate structure is achieved. This is then cleaved from the solid support by another chemical reaction into the solution within the well yielding an array of newly synthesized individual compounds, which after postreaction modification, if necessary, are suitable for testing for activity.

Apparatus and method for multiple simultaneous synthesis

A system for the multiple, simultaneous synthesis of compounds preferably uses a reaction apparatus comprising a reservoir rack having a plurality of reaction wells, a plurality of reaction tubes, usually gas dispersion tubes, having filters on their lower ends, a holder block, having a plurality of apertures, and a manifold, which has ports to allow introduction/maintenance of a controlled environment. The manifold top wall has a plurality of apertures in axial alignment with the reaction tubes and a gasket which allows penetration by a needle in order to dispense and aspirate materials from the reaction tubes. Sealing members, such as gaskets, are placed between the holder block, manifold and reservoir rack and the components are releasably fastened together. A robotic sample processor is used to automate the synthesis process using the reaction apparatus.

System for multiple simultaneous synthesis

An apparatus for multiple, simultaneous synthesis of compounds which consists of: a reservoir block having a plurality of wells; a plurality of reaction tubes, usually gas dispersion tubes, having filters on their lower ends; a holder block, having a plurality of apertures; and a manifold, which may have ports to allow introduction/maintenance of a controlled environment. The manifold top wall has apertures and a detachable plate with identical apertures. The apparatus is constructed from materials which will accommodate heating, cooling, agitation, or corrosive reagents. Gaskets are placed between the components. Rods or clamps are provided for fastening the components together. Apparatus operation involves placing the filters on the lower ends of the reaction tubes in the reservoir block wells, and the upper ends passing through the holder block apertures and into the manifold.

A method for the multiple, simultaneous synthesis of compounds comprising the steps of: 1) providing an apparatus comprising a plurality of reaction tubes having filter members on their lower ends, a reservoir member for receiving the filter member, a holder member having a plurality of apertures for supporting the reaction tubes, and a manifold member adjacent to the holder member and enclosing the upper ends of the reaction tubes; 2) charging the apparatus with reactants required for synthesis; 3) synthesizing the compounds in solution; or optionally 4) cleaving the compounds from a solid support within the apparatus.

An apparatus and method which provides a suitable location for multiple, simultaneous synthesis of compounds. The apparatus consists of: a reservoir block having a plurality of wells; a plurality of reaction tubes, usually gas dispersion tubes, having filters on their lower ends; a holder block, having a plurality of apertures; and a manifold, which my have ports to allow introduction/maintenance of a controlled environment. The manifold top wall has apertures and a detachable plate with identical apertures. The apparatus is constructed from materials which will accommodate heating, cooling, agitation, or corrosive reagents. Gaskets are placed between the components. Rods or clamps are provided for fastening the components together. Apparatus operation involves placing the filters on the lower ends of the reaction tubes in the reservoir block wells, and the upper ends passing through the holder block apertures and into the manifold. The apparatus provides in excess of 1 mg of each product with structural knowledge and control over each compound. The apparatus can be adapted to manual, semiautomatic or fully automatic performance. Using the apparatus a series of building blocks are covalently attached to a solid support. These building blocks are then modified by covalently adding additional different building blocks or chemically modifying some existing functionality until the penultimate structure is achieved. This is then cleaved from the solid support by another chemical reaction into the solution within the well yielding an array of newly synthesized individual compounds, which after postreaction modification, if necessary, are suitable for testing for activity.

Apparatus for multiple simultaneous synthesis

An apparatus and method which provides a suitable location for multiple, simultaneous synthesis of compounds. The apparatus consists of: a reservoir block having a plurality of wells; a plurality of reaction cubes, usually gas dispersion tubes, having filters on their lower ends; a holder block, having a plurality of apertures; and a manifold, which may have ports to allow introduction/maintenance of a controlled environment. The manifold top wall has apertures and a detachable place with identical apertures. The apparatus is constructed from materials which will accommodate heating, cooling, agitation, or corrosive reagents. Gaskets are placed between the components. Rods or clamps are provided for fastening the components together. Apparatus operation involves placing the filters on the lower ends of the reaction tubes in the reservoir block wells, and the upper ends passing through the holder block apertures and into the manifold. The apparatus provides in excess of 1 mg of each product with structural knowledge and control over each compound. The apparatus can be adapted to manual, semiautomatic or fully automatic performance. Using the apparatus a series of building blocks are covalently attached to a solid support. These building blocks are then modified by covalently adding additional different building blocks or chemically modifying some existing functionality until the penultimate structure is achieved. This is then cleaved from the solid support by another chemical reaction into the solution within the well yielding an array of newly synthesized individual compounds, which after postreaction modification, if necessary, are suitable for testing for activity.

An apparatus and method which provides a suitable location for multiple, simultaneous synthesis of compounds. The apparatus consists of: a reservoir block having a plurality of wells; a plurality of reaction tubes, usually gas dispersion tubes, having filters on their lower ends; a holder block, having a plurality of apertures; and a manifold, which may have ports to allow introduction/maintenance of a controlled environment. The manifold top wall has apertures and a detachable plate with identical apertures. The apparatus is constructed from materials which will accommodate heating, cooling, agitation, or corrosive reagents. Gaskets are placed between the components. Rods or clamps are provided for fastening the components together. Apparatus operation involves placing the filters on the lower ends of the reaction tubes in the reservoir block wells, and the upper ends passing through the holder block apertures and into the manifold. The apparatus provides in excess of 1 mg of each product with structural knowledge and control over each compound. Using the apparatus a series of building blocks are covalently attached to a solid support. These building blocks are then modified by covalently adding additional different building blocks or chemically modifying some existing functionality until the penultimate structure is achieved. This is then cleaved from the solid support by another chemical reaction into the solution within the well yielding an array of newly synthesized individual compounds, which after postreaction modification, if necessary, are suitable for testing for activity.

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Saline, MI, United States of America

Charles J Stankovic