1571215-33-2Relevant academic research and scientific papers
Discovery of hepatitis B virus capsid assembly inhibitors leading to a heteroaryldihydropyrimidine based clinical candidate (GLS4)
Ren, Qingyun,Liu, Xinchang,Luo, Zhonghua,Li, Jing,Wang, Chaolei,Goldmann, Siegfried,Zhang, Jiancun,Zhang, Yingjun
, p. 1042 - 1056 (2017)
Inhibition of hepatitis B virus (HBV) capsid assembly is a novel strategy for the development of chronic hepatitis B (CHB) therapeutics. Herein we described our lead optimization studies including the synthesis, molecular docking studies and structure-activity relationship (SAR) studies of a series of novel heteroaryldihydropyrimidine (HAP) inhibitors of HBV capsid assembly inhibitors, and the discovery of a potent inhibitor of HBV capsid assembly of GLS4 (ethyl 4-[2-bromo-4-fluorophenyl]-6-[morpholino-methyl]-2-[2-thiazolyl]-1,4-dihydro-pyrimidine-5-carboxylate) which is now in clinical phase 2. GLS4 demonstrated potent inhibitory activities in HBV HepG2.2.15 cell assay with an EC50value of 1 nM, and it also exhibited high potency against various drug-resistant HBV viral strains with EC50values in the range of 10–20 nM, more potent than the typical HBV polymerase inhibitors such as lamivudine, telbivudine, and entecavir. Pharmacokinetic profiles of GLS4 were favorable and safety evaluation including acute toxicity and repeated toxicity study indicated that GLS4 was safe enough to support clinical experiments in human.
Dihydropyrimidine compounds and their use in medicine
-
Paragraph 0680; 0681, (2018/04/20)
The invention relates to dihydropyrimidine compounds and application thereof in medicines, particularly application in medicines for treating and preventing hepatitis B. Particularly, the invention relates to compounds disclosed as general formula (I) or (Ia), or enantiomers, diastereoisomers, tautomerides, hydrates, solvates or pharmaceutically acceptable salts thereof, wherein the variables are defined in the specification. The invention also relates to application of the compounds disclosed as general formula (I) or (Ia), or enantiomers, diastereoisomers, tautomerides, hydrates, solvates or pharmaceutically acceptable salts thereof, especially application in medicines for treating and preventing hepatitis B.
Heteroaryl substituted dihydro pyrimidine compounds and their use in medicine
-
Paragraph 0535-0538, (2017/08/14)
The invention relates to heteroaryl-substituted dihydropyrimidine compounds and application thereof in medicines, particularly application in medicines for treating and preventing hepatitis B. Particularly, the invention relates to compounds disclosed as general formula (I) or (Ia), or enantiomers, diastereoisomers, hydrates, solvates or pharmaceutically acceptable salts thereof, wherein the variables are defined in the specification. The invention also relates to application of the compounds disclosed as general formula (I) or (Ia), or enantiomers, diastereoisomers, hydrates, solvates or pharmaceutically acceptable salts thereof, especially application in medicines for treating and preventing hepatitis B.
DIHYDROPYRIMIDINE COMPOUNDS AND THEIR APPLICATION IN PHARMACEUTICALS
-
Paragraph 0914 - 0916, (2015/06/10)
Provided herein are dihydropyrimidine compounds and their pharmaceutical applications, especially for use in treating and preventing HBV diseases. Specifically, provided herein are compounds having Formula (I) or (Ia), or an enantiomer, a diastereoisomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, wherein the variables of the formulas are as defined in the specification. Also provided herein is the use of the compounds having Formula (I) or (Ia), or an enantiomer, a diastereoisomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof for treating and preventing HBV diseases.
