Literature

Abstract

Among a small series of tested N-acylhydrazones (NAHs), the compound 8a was selected as a selective submicromolar phosphodiesterase-4 (PDE4) inhibitor associated with anti-TNF-α properties measured both in vitro and in vivo. The recognition pattern of compound 8a was elucidated through molecular modeling studies based on the knowledge of the 3D-structure of zardaverine, a PDE4 inhibitor resembling the structure of 8a, cocrystallized with the PDE4. Based on further conformational analysis dealing with N-methyl-NAHs, a quinazoline derivative (19) was designed as a conformationally constrained NAH analogue and showed similar in vitro pharmacological profile, compared with 8a. In addition 19 was found active when tested orally in LPS-evoked airway hyperreactivity and fully confirmed the working hypothesis supporting this work.

DOI： 10.1021/jm300514y

Design, Synthesis, and Pharmacological Evaluation ofN-Acylhydrazones and Novel Conformationally Constrained Compounds as Selective and Potent Orally Active Phosphodiesterase-4 Inhibitors

Journal of Medicinal Chemistry 2012.0

Design and synthesis of 4,5,6,7‐tetrahydro‐1 H ‐1,2‐diazepin‐7‐one derivatives as a new series of Phosphodiesterase 4 (PDE4) inhibitors

Bioorganic & Medicinal Chemistry Letters 2017.0

Design, synthesis and biological evaluation of 2,4-disubstituted oxazole derivatives as potential PDE4 inhibitors

Bioorganic & Medicinal Chemistry 2017.0

Design, synthesis and in vitro PDE4 inhibition activity of certain quinazolinone derivatives for treatment of asthma

Medicinal Chemistry Research 2012.0

Design, Synthesis, and Structure−Activity Relationship, Molecular Modeling, and NMR Studies of a Series of Phenyl Alkyl Ketones as Highly Potent and Selective Phosphodiesterase-4 Inhibitors

Journal of Medicinal Chemistry 2008.0

Rational design of conformationally constrained oxazolidinone-fused 1,2,3,4-tetrahydroisoquinoline derivatives as potential PDE4 inhibitors