The discovery of novel, potent and selective PDE5 inhibitors

Y Bi; P Stoy; L Adam; B He; J Krupinski; D Normandin; R Pongrac; L Seliger; A Watson; J E Macor

doi:10.1016/s0960-894x(01)00466-8

The discovery of novel, potent and selective PDE5 inhibitors

Bioorg Med Chem Lett. 2001 Sep 17;11(18):2461-4. doi: 10.1016/s0960-894x(01)00466-8.

Authors

Y Bi¹, P Stoy, L Adam, B He, J Krupinski, D Normandin, R Pongrac, L Seliger, A Watson, J E Macor

Affiliation

¹ Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA. yingzhi.bi@bms.com

PMID: 11549447
DOI: 10.1016/s0960-894x(01)00466-8

Abstract

The design and synthesis of a novel scaffold for potent and selective PDE5 inhibitors are described. Compound 3a was more potent (PDE5 IC50=0.31 nM) and selective (>10,000-fold vs PDE1 and 160-fold selective vs PDE6) PDE5 inhibitor than sildenafil.

MeSH terms

3',5'-Cyclic-GMP Phosphodiesterases
Cyclic Nucleotide Phosphodiesterases, Type 5
Cyclic Nucleotide Phosphodiesterases, Type 6
Drug Design
Drug Evaluation, Preclinical
Inhibitory Concentration 50
Phosphodiesterase Inhibitors / chemistry*
Phosphodiesterase Inhibitors / pharmacology*
Phosphoric Diester Hydrolases / drug effects*
Piperazines / pharmacology
Purines
Sildenafil Citrate
Structure-Activity Relationship
Sulfones

Substances

Phosphodiesterase Inhibitors
Piperazines
Purines
Sulfones
Sildenafil Citrate
Phosphoric Diester Hydrolases
3',5'-Cyclic-GMP Phosphodiesterases
Cyclic Nucleotide Phosphodiesterases, Type 5
Cyclic Nucleotide Phosphodiesterases, Type 6