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Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas

a diphenyl urea and kinase technology, applied in the field of aryl ureas, can solve the problems of compound structure-related toxicity, no marketed pharmaceutical agent is able to prevent or slow cartilage loss,

Inactive Publication Date: 2009-04-09
BAYER HEALTHCARE LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0122]Suitable binding materials for transdermal delivery systems are known to those skilled in the art and include polyacrylates, silicones, polyurethanes, block polymers, styrenebutadiene coploymers, and natural and synthetic rubbers. Cellulose ethers, derivatized polyethylenes, and silicates may also be used as matrix components. Additional additives, such as viscous resins or oils may be added to increase the viscosity of the matrix.

Problems solved by technology

No marketed pharmaceutical agent is able to prevent or slow this cartilage loss, although nonsteroidal antiinflammatory drugs (NSAIDs) have been given to control pain and swelling.
The end result of these diseases is total loss of joint function which is only treatable by joint replacement surgery.
Mol. Eng. 1995, 5, 143, and references therein), causing concern that these compounds may display structure-related toxicity (Howard-Martin et al.

Method used

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  • Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas
  • Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas
  • Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas

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Embodiment Construction

[0131]All reactions were performed in flame-dried or oven-dried glassware under a positive pressure of dry argon or dry nitrogen, and were stirred magnetically unless otherwise indicated. Sensitive liquids and solutions were transferred via syringe or cannula, and introduced into reaction vessels through rubber septa. Unless otherwise stated, the term ‘concentration under reduced pressure’ refers to use of a Buchi rotary evaporator at approximately 15 mmHg.

[0132]All temperatures are reported uncorrected in degrees Celsius (° C.). Unless otherwise indicated, all parts and percentages are by weight.

[0133]Commercial grade reagents and solvents were used without further purification. Thin-layer chromatography (TLC) was performed using Whatman® pre-coated glass-backed silica gel 60A F-254 250 μm plates. Visualization of plates was effected by one or more of the following techniques: (a) ultraviolet illumination, (b) exposure to iodine vapor, (c) immersion of the plate in a 10% solution o...

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Abstract

This invention relates to the use of a group of aryl ureas in treating cytokine mediated diseases and proteolytic enzyme mediated diseases, and pharmaceutical compositions for use in such therapy.

Description

[0001]This application is a continuation of U.S. Ser. No. 10 / 060,396, filed Feb. 1, 2002, which is a continuation of U.S. Ser. No. 09 / 458,015, filed Dec. 10, 1999 (now abandoned), which is a Continuation in Part of U.S. Ser. No. 09 / 285,522, filed Dec. 22, 1998 (now abandoned), which claimed priority of Provisional Application 60 / 126,439, filed Dec. 22, 1997, all of which are incorporated by reference herein.FIELD OF THE INVENTION[0002]This invention relates to the use of a group of aryl ureas in treating cytokine mediated diseases and proteolytic enzyme mediated diseases, and pharmaceutical compositions for use in such therapy.BACKGROUND OF THE INVENTION[0003]Two classes of effector molecules which are critical for the progression of rheumatoid arthritis are pro-inflammatory cytokines and tissue degrading proteases. Recently, a family of kinases was described which is instrumental in controlling the transcription and translation of the structural genes coding for these effector mole...

Claims

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Application Information

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IPC IPC(8): A61K31/40A61K31/44C07D207/36C07D213/04A61P19/02A61K31/17A61K31/341A61K31/381A61K31/4035A61K31/5375
CPCA61K31/17A61K31/341A61K31/5375A61K31/4035A61K31/44A61K31/381A61P1/00A61P11/00A61P19/02A61P19/10A61P29/00A61P41/00Y02A50/30
Inventor MILLER, SCOTTOSTERHOUT, MARTINDUMAS, JACQUESKHIRE, UDAYLOWINGER, TIMOTHY B.SCOTT, WILLIAM J.SMITH, ROGER A.WOOD, JILL E.GUNN, DAVID E.HATOUM-MOKDAD, HOLIARODRIGUEZ, MARELLSIBLEY, ROBERTWANG, MINGTURNER, TIFFANYBRENNAN, CATHERINE
Owner BAYER HEALTHCARE LLC
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