Identification, synthesis and SAR of amino substituted pyrido[3,2b]pyrazinones as potent and selective PDE5 inhibitors

Autor: Maddux Todd Michael, Yvette M. Fobian, Alan G. Benson, Dafydd R. Owen, Brian R. Bond, Christopher Phillips, Brad A. Acker, E. Jon Jacobsen, Michael John Palmer, D. Joseph Rogier, John M. Molyneaux, Brent V. Mischke, John N. Freskos, Tracy J. Ringer, Andrew Simon Bell, Blevis-Bal Radhika M, Robert Hughes, David G. Brown, Steve E. Heasley, Joseph B. Moon, John K. Walker, Brown David L, William C. Stallings, Michael B. Tollefson, Alan MacInnes, Jerry W. Cubbage, Yung Yu, Margarita Rodriquez-Lens, Fox David Nathan Abraham
Rok vydání: 2009
Předmět:
medicine.drug_mechanism_of_action
Phosphodiesterase Inhibitors
Stereochemistry
Chemistry
Pharmaceutical
Clinical Biochemistry
Pharmaceutical Science
Crystallographic data
Crystallography
X-Ray
Biochemistry
Chemical synthesis
QH301
Inhibitory Concentration 50
Structure-Activity Relationship
chemistry.chemical_compound
3'
5'-Cyclic-GMP Phosphodiesterases
Catalytic Domain
Drug Discovery
Hydrolase
medicine
Animals
Humans
QD
Molecular Biology
Cyclic Nucleotide Phosphodiesterases
Type 5
chemistry.chemical_classification
Cyclic Nucleotide Phosphodiesterases
Type 6
biology
Bicyclic molecule
Phosphoric Diester Hydrolases
Chemistry
Organic Chemistry
Hydrogen-Ion Concentration
Phosphodiesterase 5 Inhibitors
Protein Structure
Tertiary
Rats
Enzyme
Enzyme inhibitor
Drug Design
Pyrazines
biology.protein
Lactam
Molecular Medicine
Phosphodiesterase 5 inhibitor
Zdroj: Bioorganic & Medicinal Chemistry Letters. 19:4088-4091
ISSN: 0960-894X
Popis: A new class of potent and selective PDE5 inhibitors is disclosed. Guided by X-ray crystallographic data, optimization of an HTS lead led to the discovery of a series of 2-aryl, (N8)-alkyl substituted-6-aminosubstituted pyrido[3,2b]pyrazinones which show potent inhibition of the PDE5 enzyme. Synthetic details and some structure-activity relationships are also presented.
Databáze: OpenAIRE
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