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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 7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine analogue, an orally active PDE4B-selective inhibitor
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Figure 15: Structure of 7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine analogue, an orally active PDE4B-selective inhibitor

Mentions: In the year 2013, compound 32 (Figure 15) was identified as an orally active PDE4B-selective inhibitor over PDE4D both in humans (80-fold selective) and mice (29-fold selective) [54]. The therapeutic effect of compound 32 was evaluated on lipopolysaccaride (LPS) injection–induced plasma TNF-α elevation and on LPS inhalation-induced pulmonary neutrophilia in mice. The therapeutic index for TNF-α production (TITNF = ID50 in gastric emptying/ID50 in LPS injection-induced plasma TNF-α elevation) of compound 32 was larger than roflumilast (9.0 and 0.2, respectively), whereas the therapeutic index for pulmonary neutrophilia of compound 32 was comparable to roflumilast (1.0 and 0.5, respectively). Authors disclosed that the TITNF of compound 32 was not superior compared to that of roflumilast in spite of its high selectivity for PDE4B over PDE4D in mice.


Selective Phosphodiesterase 4B Inhibitors: A Review.

Azam MA, Tripuraneni NS - Sci Pharm (2014)

Structure of 7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine analogue, an orally active PDE4B-selective inhibitor
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 15: Structure of 7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine analogue, an orally active PDE4B-selective inhibitor
Mentions: In the year 2013, compound 32 (Figure 15) was identified as an orally active PDE4B-selective inhibitor over PDE4D both in humans (80-fold selective) and mice (29-fold selective) [54]. The therapeutic effect of compound 32 was evaluated on lipopolysaccaride (LPS) injection–induced plasma TNF-α elevation and on LPS inhalation-induced pulmonary neutrophilia in mice. The therapeutic index for TNF-α production (TITNF = ID50 in gastric emptying/ID50 in LPS injection-induced plasma TNF-α elevation) of compound 32 was larger than roflumilast (9.0 and 0.2, respectively), whereas the therapeutic index for pulmonary neutrophilia of compound 32 was comparable to roflumilast (1.0 and 0.5, respectively). Authors disclosed that the TITNF of compound 32 was not superior compared to that of roflumilast in spite of its high selectivity for PDE4B over PDE4D in mice.

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