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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

Novel series of imidazophenoxazine-4-sulfonamides that have shown promising PDE4B inhibitory activity
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Figure 19: Novel series of imidazophenoxazine-4-sulfonamides that have shown promising PDE4B inhibitory activity

Mentions: A number of novel imidazophenoxazine-4-sulfonamides 41a-c (Figure 19) have been designed as potential inhibitors of PDE4. Designed compounds were synthesized in a multi-step reaction process involving the construction of a 1-nitro-10H-phenoxazine ring and then fusion with an imidazole ring as the key steps [58]. Some of these compounds showed promising in vitro PDE4B and D inhibition when tested. Compounds bearing 2-hydroxyphenyl (41a), 2-bromophenyl (41b), and 5-bromo-2-fluorophenyl (41c) exhibited dose-dependent inhibition of PDE4B with IC50 values of 3.31 ± 0.62, 1.23 ± 0.18, and 0.53 ± 0.18 µM, respectively. The interaction of compound 41a with the PDE4B was mainly contributed by H-bonding between the amino group of 41a with His-278,H-bonding between the hydroxyl group of 41a and Asp392, and two π–π stacking interactions between the benzimidazole moiety and His234. Similarly, the interaction of compound 41b with the PDE4B was contributed by H-bonding between the NH2-group of 41b and Thr345, as well as Asp392, π–π stacking interactions between the central 1,4-oxazine ring and Tyr233, and π–π stacking interactions between the phenyl group of 41b and Phe446. In compound 41c, H-bonding between the amino group and Asp275 and π–π stacking interactions between the aromatic ring system and Tyr233, His234, and Phe446 residues of PDE4B was observed.


Selective Phosphodiesterase 4B Inhibitors: A Review.

Azam MA, Tripuraneni NS - Sci Pharm (2014)

Novel series of imidazophenoxazine-4-sulfonamides that have shown promising PDE4B inhibitory activity
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 19: Novel series of imidazophenoxazine-4-sulfonamides that have shown promising PDE4B inhibitory activity
Mentions: A number of novel imidazophenoxazine-4-sulfonamides 41a-c (Figure 19) have been designed as potential inhibitors of PDE4. Designed compounds were synthesized in a multi-step reaction process involving the construction of a 1-nitro-10H-phenoxazine ring and then fusion with an imidazole ring as the key steps [58]. Some of these compounds showed promising in vitro PDE4B and D inhibition when tested. Compounds bearing 2-hydroxyphenyl (41a), 2-bromophenyl (41b), and 5-bromo-2-fluorophenyl (41c) exhibited dose-dependent inhibition of PDE4B with IC50 values of 3.31 ± 0.62, 1.23 ± 0.18, and 0.53 ± 0.18 µM, respectively. The interaction of compound 41a with the PDE4B was mainly contributed by H-bonding between the amino group of 41a with His-278,H-bonding between the hydroxyl group of 41a and Asp392, and two π–π stacking interactions between the benzimidazole moiety and His234. Similarly, the interaction of compound 41b with the PDE4B was contributed by H-bonding between the NH2-group of 41b and Thr345, as well as Asp392, π–π stacking interactions between the central 1,4-oxazine ring and Tyr233, and π–π stacking interactions between the phenyl group of 41b and Phe446. In compound 41c, H-bonding between the amino group and Asp275 and π–π stacking interactions between the aromatic ring system and Tyr233, His234, and Phe446 residues of PDE4B was observed.

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