109-54-6Relevant articles and documents
Quinolinonyl Non-Diketo Acid Derivatives as Inhibitors of HIV-1 Ribonuclease H and Polymerase Functions of Reverse Transcriptase
Messore, Antonella,Corona, Angela,Madia, Valentina Noemi,Saccoliti, Francesco,Tudino, Valeria,De Leo, Alessandro,Ialongo, Davide,Scipione, Luigi,De Vita, Daniela,Amendola, Giorgio,Novellino, Ettore,Cosconati, Sandro,Métifiot, Mathieu,Andreola, Marie-Line,Esposito, Francesca,Grandi, Nicole,Tramontano, Enzo,Costi, Roberta,Di Santo, Roberto
, p. 8579 - 8598 (2021/06/30)
Novel anti-HIV agents are still needed to overcome resistance issues, in particular inhibitors acting against novel viral targets. The ribonuclease H (RNase H) function of the reverse transcriptase (RT) represents a validated and promising target, and no inhibitor has reached the clinical pipeline yet. Here, we present rationally designed non-diketo acid selective RNase H inhibitors (RHIs) based on the quinolinone scaffold starting from former dual integrase (IN)/RNase H quinolinonyl diketo acids. Several derivatives were synthesized and tested against RNase H and viral replication and found active at micromolar concentrations. Docking studies within the RNase H catalytic site, coupled with site-directed mutagenesis, and Mg2+titration experiments demonstrated that our compounds coordinate the Mg2+cofactor and interact with amino acids of the RNase H domain that are highly conserved among na?ve and treatment-experienced patients. In general, the new inhibitors influenced also the polymerase activity of RT but were selective against RNase H vs the IN enzyme.
Discovery of novel TNNI3K inhibitor suppresses pyroptosis and apoptosis in murine myocardial infarction injury
Bi, Zhiang,Chai, Jinlong,He, Gu,Pang, Haiying,Wang, Ning,Wang, Xiaoyun,Wu, Wenbin,Zhang, Yuehua
supporting information, (2020/04/27)
Myocardial infarction (MI) injury is a highly lethal syndrome that has, until recently, suffered from a lack of clinically efficient targeted therapeutics. The cardiac troponin I interacting kinase (TNNI3K) exacerbates ischemia-reperfusion (IR) injury via oxidative stress, thereby promoting cardiomyocyte death. In this current study, we designed and synthesized 35 novel TNNI3K inhibitors with a pyrido[4,5]thieno[2,3-d] pyrimidine scaffold. In vitro results indicated that some of the inhibitors exhibited sub-micromolar TNNI3K inhibitory capacity and good kinase selectivity, as well as cytoprotective activity, in an oxygen-glucose deprivation (OGD) injury cardiomyocyte model. Furthermore, investigation of the mechanism of the representative derivative compound 6o suggested it suppresses pyroptosis and apoptosis in cardiomyocytes by interfering with p38MAPK activation, which was further confirmed in a murine myocardial infarction injury model. In vivo results indicate that compound 6o can markedly reduce myocardial infarction size and alleviate cardiac tissue damage in rats. In brief, our results provide the basis for further development of novel TNNI3K inhibitors for targeted MI therapy.
Preparation method of N-dimethylaminopropyl(meth)acrylamide
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Paragraph 0046-0047, (2019/12/02)
The invention discloses a preparation method of N-dimethylaminopropyl(meth)acrylamide. The preparation method comprises the following steps: firstly, carrying out alcohol derivatization on 3-dimethylamino-1-propanol; reacting the derivatization product with (meth)acrylamide in the presence of an organic solvent and an alkali to obtain the N-dimethylaminopropyl(meth)acrylamide. Compared with a conventional preparation method adopted in the market, the preparation method disclosed by the invention has the advantages that the reaction conditions are mild, the operation is simple and convenient, the control is easy, the preparation cost is relatively low, and the commercial value is relatively high.