27115-49-7Relevant academic research and scientific papers
Synthesis and evaluation of new phenyl acrylamide derivatives as potent non-nucleoside anti-HBV agents
Gu, Xiaoke,Zhang, Yinpeng,Zou, Yueting,Li, Xin,Guan, Mingyu,Zhou, Qingqing,Qiu, Jingying
, (2020/12/09)
As a continuation of our previous work, a series of new phenyl acrylamide derivatives (4Aa-g, 4Ba-t, 5 and 6a-c) were designed and synthesized as non-nucleoside anti-HBV agents. Among them, compound 4Bs could potently inhibit HBV DNA replication in wild-type and lamivudine (3TC)/entecavir resistant HBV mutant strains with IC50 values of 0.19 and 0.18 μM, respectively. Notably, the selective index value of 4Bs was above 526, indicating the favorable safety profile. Interestingly, unlike nucleoside analogue 3TC, 4Bs could significantly inhibit 3.5 kb pgRNA expression. Molecular docking study revealed that 4Bs could fit well into the dimer-dimer interface of HBV core protein by hydrophobic, π–π and H-bond interactions. Considering the potent anti-HBV activity, low toxicity and diverse anti-HBV mechanism from that of nucleoside anti-HBV agent 3TC, compound 4Bs might be a promising lead to develop novel non-nucleoside anti-HBV therapeutic agents, and warranted further investigation.
Improvement of Oral Bioavailability of Pyrazolo-Pyridone Inhibitors of the Interaction of DCN1/2 and UBE2M
Kim, Ho Shin,Hammill, Jared T.,Scott, Daniel C.,Chen, Yizhe,Rice, Amy L.,Pistel, William,Singh, Bhuvanesh,Schulman, Brenda A.,Guy, R. Kiplin
supporting information, p. 5850 - 5862 (2021/05/29)
The cullin-RING ubiquitin ligases (CRLs) are ubiquitin E3 enzymes that play a key role in controlling proteasomal degradation and are activated by neddylation. We previously reported inhibitors that target CRL activation by disrupting the interaction of defective in cullin neddylation 1 (DCN1), a CRL neddylation co-E3, and UBE2M, a neddylation E2. Our first-generation inhibitors possessed poor oral bioavailability and fairly rapid clearance that hindered the study of acute inhibition of DCN-controlled CRL activity in vivo. Herein, we report studies to improve the pharmacokinetic performance of the pyrazolo-pyridone inhibitors. The current best inhibitor, 40, inhibits the interaction of DCN1 and UBE2M, blocks NEDD8 transfer in biochemical assays, thermally stabilizes cellular DCN1, and inhibits anchorage-independent growth in a DCN1 amplified squamous cell carcinoma cell line. Additionally, we demonstrate that a single oral 50 mg/kg dose sustains plasma exposures above the biochemical IC90 for 24 h in mice.
METHODS AND COMPOSITIONS OF INHIBITING DCN1-UBC12 INTERACTION
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Paragraph 00475, (2017/04/11)
In one aspect, the invention relates to substituted l-phenyl-3-(piperidin-4-yl)urea analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the DCN1-UBC12 interaction inhibitors of DCN1 -mediated cullin-RING ligase activity, methods of making same, pharmaceutical compositions comprising same, methods of treating disorders using the disclosed compounds and compositions, methods of treating disorders associated with a DCN1-UBC12 interaction dysfunction, methods of treating disorders associated with a DCN1-mediated cullin-RING ligase activity dysfunction, methods of male contraception comprising the disclosed compounds and compositions, and kits comprising the disclosed compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
Synthesis and Quantitative Structure-activity Relationships Study for Arylpropenamide Derivatives as Inhibitors of Hepatitis B Virus Replication
Min, Ma,Xingjun, Jiang,Xueding, Wang,Hao, Zou,Weiqing, Yang,Yuanyuan, Zhang,Changrong, Peng,Zicheng, Li,Jing, Yang,Quan, Du,Menglin, Ma
, p. 451 - 459 (2016/10/19)
A series of new arylpropenamide derivatives containing different aryl groups were synthesized, characterized, and evaluated for their anti-hepatitis B virus (HBV) activities. A new high accuracy QSAR model of arylpropenamide was constructed based on a more completely activities data and calculation parameter. The 2D-QSAR equations, by using DFT and multiple linear regression analysis methods, revealed that higher value of thermal energy (TE) and lower entropy (S?) increase the anti-HBV activities of the arylpropenamide molecules. Predictive 3D-QSAR models were established by SYBYL multifit molecular alignment rule. The optimum models were all statistically significant with cross-validated and conventional coefficients, indicating that they were reliable enough for activity prediction.
A convenient method for synthesis of 5-chloro-2-aryloxazole-4-carbaldehyde with vilsmeier reagent
Jin, Can,Chen, Jun,Su, Weike
experimental part, p. 153 - 161 (2011/04/21)
A convenient method for synthesis of 5-chloro-2-aryloxazole-4-carbaldehyde 3 in moderate to good yields had been developed via the Vilsmeier reaction of readily available N-arylglycine 2 at 100 °C, provided a novel route for the construction of nitrogen heterocycles. A series of these compounds were synthesized by this method and optimization of conditions was performed. The Japan Institute of Heterocyclic Chemistry.
A Chromogen Produced in the Reaction of Glycine Derivatives with Acetic Anhydride and Pyridine
Hirota, Kazuhiro,Ikeda, Mikiko
, p. 3100 - 3104 (2007/10/02)
The yellow chromogen produced in the assay of glutathione or glycocholic acid by their reactions with acetic anhydride and pyridine was found to be a conjugated compound containing pyridylidene and 2-oxazoline rings.The structure was confirmed by hydrolysis of the chromogen to 4-aminomethylpyridine.The same chromogen was formed with benzoylpeptides having C-terminal glycine.Keywords - chromogen; Glutathione; glycocholic acid; spectrophotometry; 2-oxazoline; pyridylidene
