2021
DOI: 10.1016/j.ejmech.2021.113174
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Discovery and development of novel pyrimidine and pyrazolo/thieno-fused pyrimidine derivatives as potent and orally active inducible nitric oxide synthase dimerization inhibitor with efficacy for arthritis

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Cited by 16 publications
(8 citation statements)
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“…The iNOS dimerization inhibitor 22o showed a promising protective effect on the cartilage both in vitro and in vivo in the present study. In our previous study, compound 22o was found to have good drug-like properties and a high oral bioavailability; additionally, the acute toxicity and subacute toxicity tests revealed the safety of the compound in vivo (Chen et al, 2021). Further long-term toxicity tests are being conducted to provide a basis for subsequent clinical trials.…”
Section: Discussionmentioning
confidence: 97%
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“…The iNOS dimerization inhibitor 22o showed a promising protective effect on the cartilage both in vitro and in vivo in the present study. In our previous study, compound 22o was found to have good drug-like properties and a high oral bioavailability; additionally, the acute toxicity and subacute toxicity tests revealed the safety of the compound in vivo (Chen et al, 2021). Further long-term toxicity tests are being conducted to provide a basis for subsequent clinical trials.…”
Section: Discussionmentioning
confidence: 97%
“…However, the current therapeutic drugs used for OA can only alleviate the symptoms; no satisfactory DMOADs are available to date. In our previous study, we demonstrated the therapeutic effect of compound 22o on Freund's adjuvant-induced rheumatoid arthritis (Chen et al, 2021), but its effect on OA remains unclear. Therefore, this study aimed to evaluate the antiinflammatory and protective effect of the compound 22o on chondrocytes and the articular cartilage, respectively, in rats with OA.…”
Section: Discussionmentioning
confidence: 98%
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“…Significantly, phthalazine-trione derivatives are well-known heterocycles used in the pharmaceutical and biological fields including vaso-relaxants, 190 antifungal, 191 antimicrobial, 192 anti-cancer, 193 and anti-inflammatory agents. 194 Besides, benzo[4,5]imidazo[1,2- a ]pyrimidines are biologically related fused pyrimidine derivatives, which demonstrate highlighted therapeutic and biological characteristics such as antimicrobial, 195 anti-inflammatory, 196 protein kinase inhibitor, 197 and anticancer. 198 …”
Section: Application Of Micro and Nanoscale Magnetic Catalytic System...mentioning
confidence: 99%
“…Molecular fluorescent probes have attracted much attention due to their high sensitivity and high selectivity, enabling accurate identification of target analytes and noninvasive real-time observation in vivo . Reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels increase during the progression of RA disease. Several fluorescent probes for the detection of reactive oxygen and nitrogen species have been reported for the diagnosis and monitoring of arthritis. , In physiological disorders, activated macrophages produce high levels of nitric oxide (NO), which can upregulate osteoclasts, destroy cartilage, and recruit other immune cells to cause inflammation, and thus NO is often thought to be involved in joint damage. Therefore, the detection of NO is of great significance for the early diagnosis of RA. , The reported NO probes are mainly composed of o -phenylenediamine and aromatic secondary amines, which specifically react with NO to produce fluorescent signals. Among them, probes with o -phenylenediamine structure are typically based on photoinduced electron transfer (PET) that undergo enhanced fluorescence in the presence of NO. Compared with to the single-channel imaging mode of the “turn-on” type probes, the ratio-metric fluorescent probes based on the intramolecular charge transfer (ICT) effect are preferred for NO imaging with high-resolution and self-calibration, which can be quantitatively detected by the ratio and effectively reduce the background signal interference to realize accurate spatial-temporal detection of NO. However, ICT-based small molecule NIR fluorescent probes with o -phenylenediamine have not been reported.…”
Section: Introductionmentioning
confidence: 99%