alexa An algorithm-directed two-component library synthesized via solid-phase methodology yielding potent and orally bioavailable p38 MAP kinase inhibitors.
Chemistry

Chemistry

Organic Chemistry: Current Research

Author(s): McKenna JM, Halley F, Souness JE, McLay IM, Pickett SD,

Abstract Share this page

Abstract Previously we reported the identification of RPR200765A, a potent orally bioavailable pyridine-imidazole inhibitor of p38 mitogen-activated protein (MAP) kinase which suppressed paw swelling and joint pathology in streptococcal cell wall-induced arthritis. Herein, we report the use of solid-phase combinatorial organic synthesis for the parallel processing of a related pyrimidine-imidazole-based library with two points of structural variability. We report also that the application of a computer algorithm, the Monte Carlo Monomer Selection, maximized both the combinatorial synthetic efficiency and the bioavailability of the final compounds. In conjunction with the synthetic protocols, the polymer-supported quench technique was applied to the purification of the final compounds. Through rapid evaluation of the library using a p38 kinase assay and permeability assays, it was possible to identify a number of potent and orally bioavailable p38 MAP kinase inhibitors suitable for further biological investigation.
This article was published in J Med Chem and referenced in Organic Chemistry: Current Research

Relevant Expert PPTs

Relevant Speaker PPTs

  • Xavier Guerrero-Pich
    Xavier-Guerrero-Pich-Polytechnical-University-of-Catalonia-Spain-Numerical-Study-on-Active-Flow-Control-using-Synthetic-Jet-Actuators-over-a-NACA-4421-Airf
    PPT Version | PDF Version
  • Alessandro Pini
    A novel synthetic antimicrobial peptide for the cure of gram-negative infections: Mechanism of action, efficacy in vivo, toxicity, bio-distribution and resistance selection
    PPT Version | PDF Version
  • K Mulkijanyan
    Plant biopolymers from Boraginaceae family species and their synthetic derivatives: Prospective pharmacological agents
    PPT Version | PDF Version
  • Manoj Kumar Chhikara
    How promising is the development of a semi-synthetic meningococcal conjugate vaccine ?
    PDF Version
  • Jianbo Wang
    Transcriptome and small RNA gene expression changes in synthetic allohexaploids of
    PPT Version | PDF Version
  • Werner Lottermoser
    Application of a Difference Electron Nanoscope (DEN): Correlation between 3D Magnetical Structures of Synthetic Fayalite with Synchrotron and Neutron Diffraction and Mössbauer Spectroscopy
    PPT Version | PDF Version
  • Jianping Yu
    Photosynthetic Ethylene Production in a Cyanobacterium
    PDF Version
  • Murad H. Al-Salamat
    Design of small synthetic molecules that mimic IL-4 binding to IL-4Rα, which therefore promotes alternate macrophage differentiation (M2) with minimal effect on the endothelial and vascular IL-4Rα.
    PDF Version

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords