Design, synthesis and biological activity of beta-carboline-based type-5 phosphodiesterase inhibitors.

Maw, Graham N; Allerton, Charlotte M N; Gbekor, Eugene; Million, William A

Maw, Graham N; Allerton, Charlotte M N; Gbekor, Eugene; Million, William A.

Affiliation

Maw GN; Department of Discovery Chemistry, Pfizer Global Research and Development, Sandwich Laboratories (IPC351), Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK. graham_maw@sandwich.pfizer.com

Bioorg Med Chem Lett ; 13(8): 1425-8, 2003 Apr 17.

Article in En | MEDLINE | ID: mdl-12668004

ABSTRACT

ABSTRACT

The SAR of a series of beta-carboline derived type 5 phosphodiesterase inhibitors has been explored and we have discovered compounds with excellent levels of PDE5 potency and selectivity over PDE6. However, the series exhibits low levels of selectivity over PDE11, a phosphodiesterase with unknown function.

Subject(s)

Carbolines/chemical synthesis; Carbolines/pharmacology; Phosphodiesterase Inhibitors/chemical synthesis; Phosphodiesterase Inhibitors/pharmacology; Phosphoric Diester Hydrolases/metabolism; 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Benzene Derivatives/chemistry; Benzene Derivatives/pharmacology; Carbolines/chemistry; Cattle; Cyclic Nucleotide Phosphodiesterases, Type 5; Dogs; Drug Design; Humans; Inhibitory Concentration 50; Isoenzymes; Phosphodiesterase Inhibitors/chemistry; Pyrrolidines/chemistry; Pyrrolidines/pharmacology; Recombinant Proteins/antagonists & inhibitors; Spodoptera; Structure-Activity Relationship

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Collection: 01-internacional Database: MEDLINE Main subject: Phosphodiesterase Inhibitors / Carbolines / Phosphoric Diester Hydrolases Limits: Animals / Humans Language: En Journal: Bioorg Med Chem Lett Journal subject: BIOQUIMICA / QUIMICA Year: 2003 Document type: Article Affiliation country: United kingdom

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