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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

Analogues of 1-(arylmethylidyne)-1,2,3,4-tetrahydro-1λ5-quinoline with PDE4B inhibitory activity
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Figure 7: Analogues of 1-(arylmethylidyne)-1,2,3,4-tetrahydro-1λ5-quinoline with PDE4B inhibitory activity

Mentions: In relation to the development of selective PDE4B inhibitors, a series of novel 1-(arylmethylidyne)-1,2,3,4-tetrahydro-1λ5-quinolines 16a–f (Figure 7), structurally related, respectively, to nimesulide and their 2-oxo analogues and 17a–f (Figure 7), have been designed and synthesized using Sonogashira coupling as a key step [43]. Synthesized compounds were evaluated in vitro for their PDE4B inhibitory activity at 30 µM. Compounds 16c and 17d, having 3-nitrophenyl and 2-chlorophenyl substituents, respectively, on the alkynyl chain attached to the nitrogen of the tetrahydroquinoline ring showed significant PDE4B inhibition (41.64 and 54.37%, respectively). Authors also presented in silico docking study results and interestingly, derivative 17c showed both electrostatic and hydrophobic interactions with the PDE4B enzyme.


Selective Phosphodiesterase 4B Inhibitors: A Review.

Azam MA, Tripuraneni NS - Sci Pharm (2014)

Analogues of 1-(arylmethylidyne)-1,2,3,4-tetrahydro-1λ5-quinoline with PDE4B inhibitory activity
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Analogues of 1-(arylmethylidyne)-1,2,3,4-tetrahydro-1λ5-quinoline with PDE4B inhibitory activity
Mentions: In relation to the development of selective PDE4B inhibitors, a series of novel 1-(arylmethylidyne)-1,2,3,4-tetrahydro-1λ5-quinolines 16a–f (Figure 7), structurally related, respectively, to nimesulide and their 2-oxo analogues and 17a–f (Figure 7), have been designed and synthesized using Sonogashira coupling as a key step [43]. Synthesized compounds were evaluated in vitro for their PDE4B inhibitory activity at 30 µM. Compounds 16c and 17d, having 3-nitrophenyl and 2-chlorophenyl substituents, respectively, on the alkynyl chain attached to the nitrogen of the tetrahydroquinoline ring showed significant PDE4B inhibition (41.64 and 54.37%, respectively). Authors also presented in silico docking study results and interestingly, derivative 17c showed both electrostatic and hydrophobic interactions with the PDE4B enzyme.

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