303066-82-2Relevant academic research and scientific papers
SUBSTITUTED BICYCLIC HETEROCYCLIC COMPOUNDS AS NADPH OXIDASE INHIBITORS
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Page/Page column 123, (2018/12/03)
The present application relates to substituted fused heteroaryl and heterocyclic compounds, useful as nicotinamide adenine dinucleotide phosphate oxidase inhibitors (NADPH oxidase inhibitors), processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment or prevention of various diseases, conditions and/or disorders mediated by NADPH oxidase. (Formula I)
Synthesis and evaluation of polycyclic pyrazolo[3,4-d]pyrimidines as PDE1 and PDE5 cGMP phosphodiesterase inhibitors
Xia, Yan,Chackalamannil, Samuel,Czarniecki, Michael,Tsai, Hsingan,Vaccaro, Henry,Cleven, Renee,Cook, John,Fawzi, Ahmad,Watkins, Robert,Zhang, Hongtao
, p. 4372 - 4377 (2007/10/03)
Polycyclic pyrazolo[3,4-d]pyrimidines (represented by 3 and 4) were synthesized as analogues of the recently reported polycyclic guanine phosphodiesterase (PDE) inhibitors. From the structure-activity relationship (SAR) development of a series of compounds, it was discovered that C-3 benzyl and N-2 methyl disubstitution on the pyrazole ring gave the best combination of potency and selectivity for PDE1 and PDE5 cGMP PDEs as represented by compound 4c: PDE1, IC50 = 60 nM; PDE3, IC50 = 55 000 nM; PDE5, IC50 = 75 nM. These compounds were also evaluated in vivo and found to be good orally active antihypertensives in laboratory animal models. Finally, comparisons were made of the in vitro and in vivo profiles of the pyrazolo- [3,4-d]pyrimidine compound 4c with those of two representative guanine compounds.
