131061-65-9Relevant academic research and scientific papers
Novel butanehydrazide derivatives of purine-2,6-dione as dual PDE4/7 inhibitors with potential anti-inflammatory activity: Design, synthesis and biological evaluation
Ch?oń-Rzepa, Gra?yna,Jankowska, Agnieszka,?lusarczyk, Marietta,?wierczek, Artur,Pociecha, Krzysztof,Wyska, El?bieta,Bucki, Adam,Gawalska, Alicja,Ko?aczkowski, Marcin,Paw?owski, Maciej
, p. 381 - 394 (2018)
A novel butanehydrazide derivatives of purine-2,6-dione designed using a ligand-based approach were synthesized and their in vitro activity against both PDE4B and PDE7A isoenzymes was assessed. The 7,8-disubstituted purine-2,6-dione derivatives 31, 34, 37, and 40 appeared to be the most potent PDE4/7 inhibitors with IC50 values in the range of that of the reference rolipram and BRL-50481, respectively. Moreover, docking studies explained the importance of N-(2,3,4-trihydroxybenzylidene)butanehydrazide substituent in position 7 of purine-2,6-dione core for dual PDE4/7 inhibitory properties. The inhibition of both the cAMP-specific PDE isoenzymes resulted in a strong anti-TNF-α effect. Compounds 31, 34, and 37 in the in vivo study in rats with LPS-induced endotoxemia decreased the maximum concentration of this proinflammatory cytokine by 53, 84 and 88%, respectively.
Synthesis and in vitro evaluation of anti-inflammatory, antioxidant, and anti-fibrotic effects of new 8-aminopurine-2,6-dione-based phosphodiesterase inhibitors as promising anti-asthmatic agents
Wójcik-Pszczo?a, Katarzyna,Jankowska, Agnieszka,?lusarczyk, Marietta,Jakie?a, Bogdan,Plutecka, Hanna,Pociecha, Krzysztof,?wierczek, Artur,Popió?, Justyna,Koczurkiewicz-Adamczyk, Paulina,Wyska, El?bieta,P?kala, El?bieta,Gosens, Reinoud,Ch?oń-Rzepa, Gra?yna
, (2021/11/11)
Phosphodiesterase (PDE) inhibitors are currently an extensively studied group of compounds that can bring many benefits in the treatment of various inflammatory and fibrotic diseases, including asthma. Herein, we describe a series of novel N’-phenyl- or N’-benzylbutanamide and N’-arylidenebutanehydrazide derivatives of 8-aminopurine-2,6-dione (27–43) and characterized them as prominent pan-PDE inhibitors. Most of the compounds exhibited antioxidant and anti-inflammatory activity in lipopolysaccharide (LPS)-induced murine macrophages RAW264.7. The most active compounds (32–35 and 38) were evaluated in human bronchial epithelial cells (HBECs) derived from asthmatics. To better map the bronchial microenvironment in asthma, HBECs after exposure to selected 8-aminopurine-2,6-dione derivatives were incubated in the presence of two proinflammatory and/or profibrotic factors: transforming growth factor type β (TGF-β) and interleukin 13 (IL-13). Compounds 32–35 and 38 significantly reduced both IL-13- and TGF-β-induced expression of proinflammatory and profibrotic mediators, respectively. Detailed analysis of their inhibition preferences for selected PDEs showed high affinity for isoenzymes important in the pathogenesis of asthma, including PDE1, PDE3, PDE4, PDE7, and PDE8. The presented data confirm that structural modifications within the 7 and 8 positions of the purine-2,6-dione core result in obtaining preferable pan-PDE inhibitors which in turn exert an excellent anti-inflammatory and anti-fibrotic effect in the bronchial epithelial cells derived from asthmatic patients. This dual-acting pan-PDE inhibitors constitute interesting and promising lead structures for further anti-asthmatic agent discovery.
Synthesis, crystal and molecular structure of 1,3-dimethyl-10-benzyl-2,4,9-trioxo-1,3,6,7,8,10-hexahydro-1,3-diazepino-purine
Karolak-Wojciechowska, Janina,Pawlowski, Maciej
, p. 477 - 482 (2007/10/02)
The crystal and molecular structure of the title compound, obtained as a result of intramolecular cyclization of 4-(8-benzylaminotheophylline-7-yl)-butanoic acid, has been determined by X-ray diffraction.Two rings, (comprising the theophylline skeleton) a
