15112-75-1Relevant articles and documents
5-Aminothiophene-2,4-dicarboxamide analogues as hepatitis B virus capsid assembly effectors
Tang, Jing,Huber, Andrew D.,Pineda, Dallas L.,Boschert, Kelsey N.,Wolf, Jennifer J.,Kankanala, Jayakanth,Xie, Jiashu,Sarafianos, Stefan G.,Wang, Zhengqiang
supporting information, p. 179 - 192 (2019/01/04)
Chronic hepatitis B virus (HBV) infection represents a major health threat. Current FDA-approved drugs do not cure HBV. Targeting HBV core protein (Cp) provides an attractive approach toward HBV inhibition and possibly infection cure. We have previously identified and characterized a 5-amino-3-methylthiophene-2,4-dicarboxamide (ATDC) compound as a structurally novel hit for capsid assembly effectors (CAEs). We report herein hit validation through studies on absorption, distribution, metabolism and excretion (ADME) properties and pharmacokinetics (PK), and hit optimization via analogue synthesis aiming to probe the structure-activity relationship (SAR) and structure-property relationship (SPR). In the end, these medicinal chemistry efforts led to the identification of multiple analogues strongly binding to Cp, potently inhibiting HBV replication in nanomolar range without cytotoxicity, and exhibiting good oral bioavailability (F). Two of our analogues, 19o (EC50 = 0.11 μM, CC50 > 100 μM, F = 25%) and 19k (EC50 = 0.31 μM, CC50 > 100 μM, F = 46%), displayed overall lead profiles superior to reported CAEs 7–10 used in our studies.
Synthesis of resveratrol acrylamides derivatives and biological evaluation of their anti-proliferative effect on cancer cell lines
Ruan, Ban-Feng,Wang, Si-Qi,Ge, Xiao-Lin,Yao, Ri-Sheng
, p. 2 - 9 (2014/01/06)
A new series of resveratrol acrylamides amine derivatives was designed, synthesized, and evaluated for their anti-proliferative activity against three cancer cell lines including human chronic myelocytic leukemia cell K562, human hepatoma HuH-7 and human lung carcinoma A549. Most of the compounds showed superior activity against three cell lines when compared to parent resveratrol. C13 had the best anti-tumor activity against the HuH-7 cell line and its IC 50 was 4.5 μmol/L; C16 had the best anti-tumor activity against the K562 cell line and its IC50 was 2.9 μmol/L; C18 had the best anti-tumor activity against the A549 cell line and its IC50 was 3.8 μmol/L. It could be seen that the activity of the aromatic amine derivatives was better than the fatty amine derivatives by analyzing the experimental data.
PYRIMIDO [4,5-B]QUINOLINE-4,5 (3H,10H)-DIONES AS NONSENSE MUTATION SUPPRESSORS
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Page/Page column 57, (2014/07/07)
The invention relates to compound of the formula (I); or a salt thereof, wherein the substituents are as defined in the specification; to its preparation, to its use as medicament and to medicaments comprising it.
