PMID- 16388517
OWN - NLM
STAT- MEDLINE
DCOM- 20061215
LR  - 20071115
IS  - 0198-6325 (Print)
IS  - 0198-6325 (Linking)
VI  - 26
IP  - 3
DP  - 2006 May
TI  - Phosphodiesterase 5 (PDE 5) inhibitors for the treatment of male erectile 
      disorder: attaining selectivity versus PDE6.
PG  - 369-95
AB  - The role of phosphodiesterase type 5 (PDE5) in the mechanism of male erection has 
      been well understood, and several drugs inhibiting this enzyme are being used for 
      the treatment of erectile dysfunction (ED). Discovery of inhibitors with improved 
      selectivity versus other PDE isozymes could lead to drugs with improved safety 
      profile. Achievement of selectivity versus PDE6, co-inhibition of which results 
      in disturbances of color perception, remains the most challenging aspect of 
      current drug discovery programs. The present review describes several case 
      studies, where significant (>100 fold) selectivity versus PDE6 has been attained 
      via investigation of structure-activity relationships (SAR). Special attention is 
      given to the chemical routes leading to novel chemotypes and allowing efficient 
      exploration of their SAR's. Strategies for attaining inhibitor selectivity 
      discussed below may be applicable for other drug discovery programs.
CI  - Copyright 2005 Wiley Periodicals, Inc.
FAU - Pissarnitski, Dmitri
AU  - Pissarnitski D
AD  - Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. 
      Dmitri.Pissarnitski@spcorp.com
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Med Res Rev
JT  - Medicinal research reviews
JID - 8103150
RN  - 0 (Enzyme Inhibitors)
RN  - EC 3.1.4.- (Phosphoric Diester Hydrolases)
RN  - EC 3.1.4.35 (3',5'-Cyclic-GMP Phosphodiesterases)
RN  - EC 3.1.4.35 (Cyclic Nucleotide Phosphodiesterases, Type 5)
RN  - EC 3.1.4.35 (Cyclic Nucleotide Phosphodiesterases, Type 6)
RN  - EC 3.1.4.35 (PDE5A protein, human)
RN  - EC 3.1.4.35 (PDE6B protein, human)
SB  - IM
MH  - 3',5'-Cyclic-GMP Phosphodiesterases/*antagonists & inhibitors/metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 5
MH  - Cyclic Nucleotide Phosphodiesterases, Type 6
MH  - Enzyme Inhibitors/*pharmacology/*therapeutic use
MH  - Erectile Dysfunction/*drug therapy
MH  - Humans
MH  - Male
MH  - Models, Molecular
MH  - Phosphoric Diester Hydrolases/*metabolism
MH  - Sensitivity and Specificity
RF  - 100
EDAT- 2006/01/03 09:00
MHDA- 2006/12/16 09:00
CRDT- 2006/01/03 09:00
PHST- 2006/01/03 09:00 [pubmed]
PHST- 2006/12/16 09:00 [medline]
PHST- 2006/01/03 09:00 [entrez]
AID - 10.1002/med.20053 [doi]
PST - ppublish
SO  - Med Res Rev. 2006 May;26(3):369-95. doi: 10.1002/med.20053.