76477-26-4Relevant articles and documents
Identification of potent and selective hydantoin inhibitors of aggrecanase-1 and aggrecanase-2 that are efficacious in both chemical and surgical models of osteoarthritis
Durham, Timothy B.,Klimkowski, Valentine J.,Rito, Christopher J.,Marimuthu, Jothirajah,Toth, James L.,Liu, Chin,Durbin, Jim D.,Stout, Stephanie L.,Adams, Lisa,Swearingen, Craig,Lin, Chaohua,Chambers, Mark G.,Thirunavukkarasu, Kannan,Wiley, Michael R.
, p. 10476 - 10485 (2014)
A disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and ADAMTS-5 are zinc metalloproteases commonly referred to as aggrecanase-1 and aggrecanase-2, respectively. These enzymes are involved in the degradation of aggrecan, a key component of cartilage. Inhibitors of these enzymes could be potential osteoarthritis (OA) therapies. A series of hydantoin inhibitors of ADAMTS-4 and ADAMTS-5 were identified from a screening campaign and optimized through structure-based drug design to give hydantoin 13. Hydantoin 13 had excellent selectivity over other zinc metalloproteases such as TACE, MMP2, MMP3, MMP13, and MMP14. The compound also produced efficacy in both a chemically induced and surgical model of OA in rats.
Improving the metabolic stability of antifungal compounds based on a scaffold hopping strategy: Design, synthesis, and structure-activity relationship studies of dihydrooxazole derivatives
Cheng, Maosheng,Su, Xin,Sun, Nannan,Sun, Yin,Tian, Linfeng,Yin, Wenbo,Zhang, Chu,Zhao, Dongmei,Zhao, Liyu,Zhao, Shizhen,Zheng, Yang
, (2021/08/07)
L-amino alcohol derivatives exhibited high antifungal activity, but the metabolic stability of human liver microsomes in vitro was poor, and the half-life of optimal compound 5 was less than 5 min. To improve the metabolic properties of the compounds, the scaffold hopping strategy was adopted and a series of antifungal compounds with a dihydrooxazole scaffold was designed and synthesized. Compounds A33-A38 substituted with 4-phenyl group on dihydrooxazole ring exhibited excellent antifungal activities against C. albicans, C. tropicalis and C. krusei, with MIC values in the range of 0.03–0.25 μg/mL. In addition, the metabolic stability of compounds A33 and A34 in human liver microsomes in vitro was improved significantly, with the half-life greater than 145 min and the half-life of 59.1 min, respectively. Moreover, pharmacokinetic studies in SD rats showed that A33 exhibited favourable pharmacokinetic properties, with a bioavailability of 77.69%, and half-life (intravenous administration) of 9.35 h, indicating that A33 is worthy of further study.
Copper-catalyzed borylative aminomethylation of C-C double and triple bonds withN,O-acetal
Qiu, Xianfan,Xu, Liugen,Wang, Shuxia,Dai, Ying,Feng, Yunqiu,Gong, Chang,Tao, Chuanzhou
, p. 3279 - 3282 (2021/04/07)
A copper-catalyzed borylaminomethylation of multiple carbon-carbon bonds withN,O-acetal and bis(pinacolato)diboron has been disclosed that offers efficient and expedient access to γ-amino boronates. The products contain a valuable amine and boronate, whic
