Warner-lambert Company

Other

Mel C Schroeder

John S Kiely

Michael R Pavia

Sheila H DeWitt

Charles J Stankovic

John Michael Domagala

Donna Reynolds Cody

Edgardo Laborde

Haile Tecle

Stephen Douglas Barrett

Alexander James Bridges

Annette Marian Doherty

Alan Robert Saltiel

James Marino Hamby

David Thomas Dudley

Bruce D Roth

Walter H Moos

John C Hodges

Annette M Doherty

Howard D Showalter

Clifton J Blankley

Robert Lee Panek

Cleo Connolly

James Bernard Kramer

Peter Laurence Toogood

Clarke Bentley Taylor

Ellen Myra Dobrusin

Chris Limberakis

Howard Daniel Hollis Showalter

Denton Wade Hoyer

Jessica Elizabeth Reed

Steven Ware

Michael Kell

Susanne A Trumpp-Kallmeyer

Cleo J Chivikas Connolly

Lawrence E Lesheski

Christopher James Deur

This invention provides substituted pyrimido-pyrimidines that are useful for treating cell proliferative disorders, such as cancer and restenosis, as well as angiogenesis and atherosclerosis. The invention compounds have Formula I: where The invention also provides pharmaceutical formulations comprising a compound of Formula I together with a pharmaceutically acceptable carrier, diluent, or excipient therefor, and a method for treating angiogenesis using said compounds.

Bicyclic pyrimidines and bicyclic 3,4-dihydropyprimidines as inhibitors of cellular proliferation

This invention provides phenyl-substituted pyrimidopyrimidines, dihydropyrimido-pyrimidines, pyridopyrimidines, naphthyridines, and pyridopyrazines of the general formula: that inhibit cyclin-dependent kinase and tyrosine kinase enzymes, methods and intermediate compounds for their synthesis, as well as pharmaceutical compositions and methods for their use in treating, inhibiting or preventing maladies associated with cell proliferative disorders, including angiogenesis, atherosclerosis, restenosis, and cancer.

Kinase inhibitors

Phenylamino benzoic acid, benzamides, and benzyl alcohol derivatives of the formula

2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives

2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives and their use as MEK inhibitors

The present invention provides a method for treating or preventing septic shock. Specifically, the present invention provides a method of treating or preventing septic shock by administering to a patient a MEK inhibitor.

Method of treating or preventing septic shock by administering a MEK inhibitor

6-Aryl naphthyridines are inhibitors of protein tyrosine kinase, and are thus useful in treating cellular proliferation mediated thereby. The compounds are especially useful in treating atherosclerosis, restenosis, psoriasis, as well as bacterial infections.

6-aryl naphthyridines for inhibiting protein tyrosine kinase mediated

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

6-Aryl pyrido�2,3-d!pyrimidines and naphthyridines are inhibitors of protein tyrosine kinase, and are thus useful in treating cellular proliferation mediated thereby. The compounds are especially useful in treating atherosclerosis, restenosis, psoriasis, as well as bacterial infections.

6-Aryl pyrido�2,3-d! pyrimidines and naphthyridines for inhibiting

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.

Individual stereoisomers of 7-[3-(1-aminoalkyl)-1-pyrrolidinyl]-quinolones and naphthyridones are described, their therapeutic advantages as antibacterial agents, as well as a novel method for the preparation and isolation of such stereoisomers.

Individual stereoisomers of

A compound of the formula ##STR1## wherein * denotes an asymmetric carbon; X is C--H, C--F, C--Cl, C--OCH.sub.3, C--CF.sub.3, or N;

7-substituted quinolones and naphthyridones as antibacterial agents

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.

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Dexter, MI, United States of America

Mel C Schroeder