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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 hexahydrophthalazinone that have shown promising PDE4B2 inhibitory activity
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Figure 10: Analogues of hexahydrophthalazinone that have shown promising PDE4B2 inhibitory activity

Mentions: Inspired by the development of multifunctional drugs, a new series of phthalazine analogues 21 and 22a–d (Figure 10) is described [48] for the treatment of both asthma and COPD, which could target the β2-adrenoceptor and PDE4B2. Synthesized compounds 21 and 22a–d exhibited PDE4B2 IC50 values of 0.520, 0.280, 0.278, 0.257, and 0.251 µM, respectively. Authors disclosed that the hexyl chain linking the hexahydrophthalazinone and N-[5-(2-aminoethyl)-2-hydroxyphenyl]formamide moieties (22d) is optimum for PDE4B2 inhibition. The synthesized compounds were also tested for guinea pig tracheal chain relaxation. Derivative (R)-(22b) showed significant relaxant effects on histamine-induced guinea pig tracheal chain contractions (pEC50 9.3) compared to the reference drug isoprenaline (pEC50 7.5).


Selective Phosphodiesterase 4B Inhibitors: A Review.

Azam MA, Tripuraneni NS - Sci Pharm (2014)

Analogues of hexahydrophthalazinone that have shown promising PDE4B2 inhibitory activity
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 10: Analogues of hexahydrophthalazinone that have shown promising PDE4B2 inhibitory activity
Mentions: Inspired by the development of multifunctional drugs, a new series of phthalazine analogues 21 and 22a–d (Figure 10) is described [48] for the treatment of both asthma and COPD, which could target the β2-adrenoceptor and PDE4B2. Synthesized compounds 21 and 22a–d exhibited PDE4B2 IC50 values of 0.520, 0.280, 0.278, 0.257, and 0.251 µM, respectively. Authors disclosed that the hexyl chain linking the hexahydrophthalazinone and N-[5-(2-aminoethyl)-2-hydroxyphenyl]formamide moieties (22d) is optimum for PDE4B2 inhibition. The synthesized compounds were also tested for guinea pig tracheal chain relaxation. Derivative (R)-(22b) showed significant relaxant effects on histamine-induced guinea pig tracheal chain contractions (pEC50 9.3) compared to the reference drug isoprenaline (pEC50 7.5).

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