Document Detail


Design, synthesis and SAR of phenylamino-substituted 5,11-dihydro-dibenzo[a,d]cyclohepten-10-ones and 11H-dibenzo[b,f]oxepin-10-ones as p38 MAP kinase inhibitors.
MedLine Citation:
PMID:  20418099     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The p38 MAP kinase is a key enzyme in inflammatory diseases as it is involved in the biosynthesis of proinflammatory cytokines such as TNF-alpha and IL-1beta. Small molecule p38 inhibitors suppress the production of these cytokines and therefore p38 is a promising drug target for novel anti-inflammatory therapeutics. In this study, we report the design, synthesis, and SAR of novel N-substituted 11H-dibenzo[b,f]oxepin-10-ones and 5,11-dihydro-dibenzo[a,d]cyclohepten-10-ones as p38 inhibitors.
Authors:
Angelika Dorn; Verena Schattel; Stefan Laufer
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Publication Detail:
Type:  Journal Article     Date:  2010-04-01
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  20     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-04     Completed Date:  2010-08-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  3074-7     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Institute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Anti-Inflammatory Agents
Binding Sites
Computer Simulation
Cycloheptanes / chemical synthesis,  chemistry*,  pharmacology
Drug Design
Interleukin-1beta / metabolism
Oxepins / chemical synthesis,  chemistry*,  pharmacology
Protein Kinase Inhibitors / chemical synthesis,  chemistry*,  pharmacology
Structure-Activity Relationship
Tumor Necrosis Factor-alpha / metabolism
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*,  metabolism
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Cycloheptanes; 0/Interleukin-1beta; 0/Oxepins; 0/Protein Kinase Inhibitors; 0/Tumor Necrosis Factor-alpha; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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