Biology Reference
In-Depth Information
(R)
(S)
rolipram
roflumilast
vardenafil
sildenafil
tadalafil
papaverine
RS-25344
BAY 73-6691
Fig. 6 Structure of the most common nonselective or family-specific PDE inhibitors. Rolipram,
Roflumilast and RS25344 are PDE4-selective. The two enantiomers of rolipram [(
R
)-(
)-rolipram
(the more potent enantiomer of rolipram) and (
S
)-(
รพ
)-rolipram (the less potent enantiomer of
rolipram)] are indicated as (
R
) and (
S
), respectively. Vardenafil, sildenafil, and tadalafil are PDE5-
selective, although vardenafil and sildenafil are potent inhibitors of PDE6. BAY 73-6691 is selec-
tive for PDE9. Papaverine is nonselective but has high affinity for PDE10
Guided by insights derived fromX-ray crystal structures of various PDE catalytic
sites as well as GAFs and UCR domains, chemists are now systematically exploiting
features that provide for novel drug designs exhibiting greater specificity and
potency. Structural information that is available for many isolated catalytic domains
reveals new insights into specific topographical features of particular catalytic sites.
Much effort is now being devoted to utilization of this new information for
