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The discovery and synthesis of highly potent subtype selective phosphodiesterase 4D inhibitors.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Sep 15; Vol. 20 (18), pp. 5502-5. Date of Electronic Publication: 2010 Jul 21. - Publication Year :
- 2010
-
Abstract
- The SAR study of a series of 6-aryloxymethyl-8-aryl substituted quinolines is described. Optimization of the series led to the discovery of compound 26b, a highly potent (IC50=0.6 nM) and selective PDE4D inhibitor with a 75-fold selectivity over the A, B, and C subtypes and over 18,000-fold selectivity against other PDE family members. Rat pharmacokinetics and tissue distribution are also summarized.<br /> (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Asthma drug therapy
Humans
Inhibitory Concentration 50
Male
Phosphodiesterase Inhibitors chemical synthesis
Phosphodiesterase Inhibitors pharmacokinetics
Quinolines chemical synthesis
Quinolines pharmacokinetics
Rats
Rats, Wistar
Structure-Activity Relationship
Cyclic Nucleotide Phosphodiesterases, Type 4 metabolism
Phosphodiesterase Inhibitors chemistry
Phosphodiesterase Inhibitors pharmacology
Quinolines chemistry
Quinolines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 20
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 20709547
- Full Text :
- https://doi.org/10.1016/j.bmcl.2010.07.076