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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 1,4-dihydropyridine analogues that have Ca2+ channel blocking and
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Figure 25: Structure of 1,4-dihydropyridine analogues that have Ca2+ channel blocking and

Mentions: In another study, a novel series of 1,4-dihydropyridine-based PDE4B inhibitors were synthesized [77] and evaluated for their in vitro Ca2+ channel blocking and PDE4B inhibitory activities. Compounds 50a-g (Figure 25) exhibited >80% inhibition of PDE4B. Among the synthesized inhibitors, 50d, having an indaloyl moiety, exhibited significant selectivity towards PDE4B with a docking score of −8.1 kcal/mol. The in silico docking result of compound 50d supported the reason for the selectivity, where the indole moiety exists in two different orientations in PDE4D, and in both cases, it makes a stronger hydrogen bond with Glu396 or Glu505 residues of PDE4D, while its orientation in PDE4B is completely different than that in PDE4D. The dimethoxy group of 50d interacted with the metal atoms in PDE4B, while the indole moiety was shown to be H-bonded with the Ser442 backbone.


Selective Phosphodiesterase 4B Inhibitors: A Review.

Azam MA, Tripuraneni NS - Sci Pharm (2014)

Structure of 1,4-dihydropyridine analogues that have Ca2+ channel blocking and
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 25: Structure of 1,4-dihydropyridine analogues that have Ca2+ channel blocking and
Mentions: In another study, a novel series of 1,4-dihydropyridine-based PDE4B inhibitors were synthesized [77] and evaluated for their in vitro Ca2+ channel blocking and PDE4B inhibitory activities. Compounds 50a-g (Figure 25) exhibited >80% inhibition of PDE4B. Among the synthesized inhibitors, 50d, having an indaloyl moiety, exhibited significant selectivity towards PDE4B with a docking score of −8.1 kcal/mol. The in silico docking result of compound 50d supported the reason for the selectivity, where the indole moiety exists in two different orientations in PDE4D, and in both cases, it makes a stronger hydrogen bond with Glu396 or Glu505 residues of PDE4D, while its orientation in PDE4B is completely different than that in PDE4D. The dimethoxy group of 50d interacted with the metal atoms in PDE4B, while the indole moiety was shown to be H-bonded with the Ser442 backbone.

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