1206113-96-3Relevant academic research and scientific papers
Design, synthesis, and pharmacological evaluation of N-acylhydrazones and novel conformationally constrained compounds as selective and potent orally active phosphodiesterase-4 inhibitors
Kümmerle, Arthur E.,Schmitt, Martine,Cardozo, Suzana V. S.,Lugnier, Claire,Villa, Pascal,Lopes, Alexandra B.,Romeiro, Nelilma C.,Justiniano, Hélène,Martins, Marco A.,Fraga, Carlos A. M.,Bourguignon, Jean-Jacques,Barreiro, Eliezer J.
, p. 7525 - 7545 (2012/11/06)
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.
