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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

Cyano pyridine derivatives with PDE4B inhibitory activity
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Figure 13: Cyano pyridine derivatives with PDE4B inhibitory activity

Mentions: Green synthesis of functionalized cyano pyridines 28a–e (Figure 13) as novel PDE4B inhibitors has been described via the montmorillonite K-10-mediated multi-component reaction in a chemo- and regioselective manner [52]. The synthesized compounds were evaluated for their PDE4B inhibitory potency at 30 µM using rolipram as the standard. The in vitro results revealed that a strong electron donating group such as OCH3 at the para position of the benzene ring in 28a (percentage inhibition 64.10) and 28b (percentage inhibition 65.0) was optimum for the activity compared to other milder electron donating groups such as F or Br (28c–e) (percentage inhibition <45). The di- or tri- substitution on the C-4 benzene ring resulted in the loss of PDE4B inhibitory activity. In silico docking studies showed the binding affinities of compounds 28a and 28c with a docking score of −25.47 and −17.8 kcal/mol, respectively. The cyano group of compound 28c formed H-bonding with HIS234 of the PDE4B isoenzyme. However, it was the OCH3 group in 28a that formed H-bonding with the Glu443 residue of PDE4B. In addition, it also showed an arene-arene interaction with the Phe446 residue.


Selective Phosphodiesterase 4B Inhibitors: A Review.

Azam MA, Tripuraneni NS - Sci Pharm (2014)

Cyano pyridine derivatives with PDE4B inhibitory activity
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 13: Cyano pyridine derivatives with PDE4B inhibitory activity
Mentions: Green synthesis of functionalized cyano pyridines 28a–e (Figure 13) as novel PDE4B inhibitors has been described via the montmorillonite K-10-mediated multi-component reaction in a chemo- and regioselective manner [52]. The synthesized compounds were evaluated for their PDE4B inhibitory potency at 30 µM using rolipram as the standard. The in vitro results revealed that a strong electron donating group such as OCH3 at the para position of the benzene ring in 28a (percentage inhibition 64.10) and 28b (percentage inhibition 65.0) was optimum for the activity compared to other milder electron donating groups such as F or Br (28c–e) (percentage inhibition <45). The di- or tri- substitution on the C-4 benzene ring resulted in the loss of PDE4B inhibitory activity. In silico docking studies showed the binding affinities of compounds 28a and 28c with a docking score of −25.47 and −17.8 kcal/mol, respectively. The cyano group of compound 28c formed H-bonding with HIS234 of the PDE4B isoenzyme. However, it was the OCH3 group in 28a that formed H-bonding with the Glu443 residue of PDE4B. In addition, it also showed an arene-arene interaction with the Phe446 residue.

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