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Selective Phosphodiesterase 4B Inhibitors: A Review.

Azam MA, Tripuraneni NS - Sci Pharm (2014)

Bottom Line: Phosphodiesterase 4B has constituted an interesting target for drug development.In recent years, a number of PDE4B inhibitors have been developed for their use as therapeutic agents.In this review, an up-to-date status of the inhibitors investigated for the inhibition of PDE4B has been given so that this rich source of structural information of presently known PDE4B inhibitors could be helpful in generating a selective and potent inhibitor of PDE4B.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, J. S. S. College of Pharmacy, Ootacamund-643001, Tamil Nadu, India.

ABSTRACT
Phosphodiesterase 4B (PDE4B) is a member of the phosphodiesterase family of proteins that plays a critical role in regulating intracellular levels of cyclic adenosine monophosphate (cAMP) by controlling its rate of degradation. It has been demonstrated that this isoform is involved in the orchestra of events which includes inflammation, schizophrenia, cancers, chronic obstructive pulmonary disease, contractility of the myocardium, and psoriatic arthritis. Phosphodiesterase 4B has constituted an interesting target for drug development. In recent years, a number of PDE4B inhibitors have been developed for their use as therapeutic agents. In this review, an up-to-date status of the inhibitors investigated for the inhibition of PDE4B has been given so that this rich source of structural information of presently known PDE4B inhibitors could be helpful in generating a selective and potent inhibitor of PDE4B.

No MeSH data available.


Related in: MedlinePlus

1,3,4-oxadiazole and 1,2,4-oxadiazole containing 1-ethyl-1H-pyrazolo[3,4-b]-pyridines with PDE4B inhibitory activity
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Figure 14: 1,3,4-oxadiazole and 1,2,4-oxadiazole containing 1-ethyl-1H-pyrazolo[3,4-b]-pyridines with PDE4B inhibitory activity

Mentions: 1,3,4-oxadiazole and 1,2,4-oxadiazole containing 1-ethyl-1H-pyrazolo[3,4-b]pyridines 29a–d and 30a–d (Figure 14) have been explored as potent PDE4B inhibitors [39] (pIC508.0–8.7 and 7.8–9.4, respectively) taking into account the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective PDE4B inhibitors [37]. The structure-activity relationship of fifth 5-position was studied [53] further. Preliminary structure–activity studies were conducted against isolated PDE4B, the predominant PDE4 subtype in inflammatory cells of interest. Results indicated that both oxadiazole isomers were tolerated at fifth position. Different oxadiazole substituents showed significant potency in each series, but unfortunately no structure-activity relationship was established. Further di-substituted and mono-substituted oxazoles 31a and 31b (Figure 14) were also synthesized. The di-substituted oxazole 31a demonstrated sub-nM activity in the isolated enzyme and isolated human peripheral blood mononuclear cells (PBMC) assay and gave at least a 10-fold increase in potency over 1,3,4-oxadiazole 13c and 1,2,4-oxadiazole 29b. Moreover, in compound 31a, the introduction of a second substituent showed an increase in potency in comparison to the mono-substituted oxazole 31b.


Selective Phosphodiesterase 4B Inhibitors: A Review.

Azam MA, Tripuraneni NS - Sci Pharm (2014)

1,3,4-oxadiazole and 1,2,4-oxadiazole containing 1-ethyl-1H-pyrazolo[3,4-b]-pyridines with PDE4B inhibitory activity
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4318138&req=5

Figure 14: 1,3,4-oxadiazole and 1,2,4-oxadiazole containing 1-ethyl-1H-pyrazolo[3,4-b]-pyridines with PDE4B inhibitory activity
Mentions: 1,3,4-oxadiazole and 1,2,4-oxadiazole containing 1-ethyl-1H-pyrazolo[3,4-b]pyridines 29a–d and 30a–d (Figure 14) have been explored as potent PDE4B inhibitors [39] (pIC508.0–8.7 and 7.8–9.4, respectively) taking into account the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective PDE4B inhibitors [37]. The structure-activity relationship of fifth 5-position was studied [53] further. Preliminary structure–activity studies were conducted against isolated PDE4B, the predominant PDE4 subtype in inflammatory cells of interest. Results indicated that both oxadiazole isomers were tolerated at fifth position. Different oxadiazole substituents showed significant potency in each series, but unfortunately no structure-activity relationship was established. Further di-substituted and mono-substituted oxazoles 31a and 31b (Figure 14) were also synthesized. The di-substituted oxazole 31a demonstrated sub-nM activity in the isolated enzyme and isolated human peripheral blood mononuclear cells (PBMC) assay and gave at least a 10-fold increase in potency over 1,3,4-oxadiazole 13c and 1,2,4-oxadiazole 29b. Moreover, in compound 31a, the introduction of a second substituent showed an increase in potency in comparison to the mono-substituted oxazole 31b.

Bottom Line: Phosphodiesterase 4B has constituted an interesting target for drug development.In recent years, a number of PDE4B inhibitors have been developed for their use as therapeutic agents.In this review, an up-to-date status of the inhibitors investigated for the inhibition of PDE4B has been given so that this rich source of structural information of presently known PDE4B inhibitors could be helpful in generating a selective and potent inhibitor of PDE4B.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, J. S. S. College of Pharmacy, Ootacamund-643001, Tamil Nadu, India.

ABSTRACT
Phosphodiesterase 4B (PDE4B) is a member of the phosphodiesterase family of proteins that plays a critical role in regulating intracellular levels of cyclic adenosine monophosphate (cAMP) by controlling its rate of degradation. It has been demonstrated that this isoform is involved in the orchestra of events which includes inflammation, schizophrenia, cancers, chronic obstructive pulmonary disease, contractility of the myocardium, and psoriatic arthritis. Phosphodiesterase 4B has constituted an interesting target for drug development. In recent years, a number of PDE4B inhibitors have been developed for their use as therapeutic agents. In this review, an up-to-date status of the inhibitors investigated for the inhibition of PDE4B has been given so that this rich source of structural information of presently known PDE4B inhibitors could be helpful in generating a selective and potent inhibitor of PDE4B.

No MeSH data available.


Related in: MedlinePlus