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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

Structure of the 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine analogue that has shown highly selective PDE4B inhibition
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Figure 22: Structure of the 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine analogue that has shown highly selective PDE4B inhibition

Mentions: In search of highly selective PDE4B inhibitors, a novel series of 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidines were synthesized and evaluated for their PDE4B subtype selectivity using human PDE4B2 and PDE4D2 full-length enzymes [61]. The molecules were optimized by varying the substituents on the pyrimidine ring and the phenyl ring present over the side chain. The in vitro screening of the synthesized compounds resulted in the identification of 2-(3-chloro-4-methoxyphenyl)-5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine (47) (Figure 22) as a highly selective PDE4B inhibitor, which showed PDE4B inhibitory activity with an IC50 value of 3.0 nM and 433-fold PDE4B selectivity over PDE4D.


Selective Phosphodiesterase 4B Inhibitors: A Review.

Azam MA, Tripuraneni NS - Sci Pharm (2014)

Structure of the 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine analogue that has shown highly selective PDE4B inhibition
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 22: Structure of the 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine analogue that has shown highly selective PDE4B inhibition
Mentions: In search of highly selective PDE4B inhibitors, a novel series of 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidines were synthesized and evaluated for their PDE4B subtype selectivity using human PDE4B2 and PDE4D2 full-length enzymes [61]. The molecules were optimized by varying the substituents on the pyrimidine ring and the phenyl ring present over the side chain. The in vitro screening of the synthesized compounds resulted in the identification of 2-(3-chloro-4-methoxyphenyl)-5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine (47) (Figure 22) as a highly selective PDE4B inhibitor, which showed PDE4B inhibitory activity with an IC50 value of 3.0 nM and 433-fold PDE4B selectivity over PDE4D.

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