PDE4 Inhibitors: Profiling Hits through the Multitude of Structural Classes

被引：14

作者：

Jin, Jian ^{[1
]}

Mazzacuva, Francesca ^{[2
]}

Crocetti, Letizia ^{[3
]}

Giovannoni, Maria Paola ^{[3
]}

Cilibrizzi, Agostino ^{[1
,4
]}

机构：

[1] Kings Coll London, Inst Pharmaceut Sci, Stamford St, London SE1 9NH, England

[2] Univ East London, Sch Hlth Sport & Biosci, London E15 4LZ, England

[3] Univ Florence, Neurofarba Dept, Pharmaceut & Nutraceut Sect, Via Ugo Schiff 6, I-50019 Florence, Italy

[4] Univ Bath, Ctr Therapeut Innovat, Bath BA2 7AY, England

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 14期

关键词：

phosphodiesterases; 4; PDE4; inhibitors; structural analysis; selectivity; respiratory diseases; dual activity; SELECTIVE PHOSPHODIESTERASE-4 INHIBITOR; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; PYRIDAZINONE DERIVATIVES; BIOLOGICAL EVALUATION; IV INHIBITORS; DISCOVERY; DESIGN; PHARMACOLOGY; EXPRESSION; BINDING;

D O I：

10.3390/ijms241411518

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cyclic nucleotide phosphodiesterases 4 (PDE4) are a family of enzymes which specifically promote the hydrolysis and degradation of cAMP. The inhibition of PDE4 enzymes has been widely investigated as a possible alternative strategy for the treatment of a variety of respiratory diseases, including chronic obstructive pulmonary disease and asthma, as well as psoriasis and other autoimmune disorders. In this context, the identification of new molecules as PDE4 inhibitors continues to be an active field of investigation within drug discovery. This review summarizes the medicinal chemistry journey in the design and development of effective PDE4 inhibitors, analyzed through chemical classes and taking into consideration structural aspects and binding properties, as well as inhibitory efficacy, PDE4 selectivity and the potential as therapeutic agents.

引用

页数：20

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