298709-35-0Relevant academic research and scientific papers
Synthesis and antiviral evaluation of novel heteroarylpyrimidines analogs as HBV capsid effectors
Boucle, Sebastien,Lu, Xiao,Bassit, Leda,Ozturk, Tugba,Russell, Olivia Ollinger,Amblard, Franck,Coats, Steven J.,Schinazi, Raymond F.
, p. 904 - 910 (2017/02/10)
New modifications to the scaffold of previously reported HBV capsid assembly effectors such as BAY 41-4109, HAP-12 and GLS4 were explored. The anti-HBV activity in the HepAD38 system, and cytotoxicity profiles of each of the new compounds has been assessed. Among them, five new iodo- and bromo-heteroarylpyrimidines analogs displayed anti-HBV activity in the low micromolar range.
Design and synthesis of orally bioavailable 4-methyl heteroaryldihydropyrimidine based hepatitis B virus (HBV) capsid inhibitors
Qiu, Zongxing,Lin, Xianfeng,Zhou, Mingwei,Liu, Yongfu,Zhu, Wei,Chen, Wenming,Zhang, Weixing,Guo, Lei,Liu, Haixia,Wu, Guolong,Huang, Mengwei,Jiang, Min,Xu, Zhiheng,Zhou, Zheng,Qin, Ning,Ren, Shuang,Qiu, Hongxia,Zhong, Sheng,Zhang, Yuxia,Zhang, Yi,Wu, Xiaoyue,Shi, Liping,Shen, Fang,Mao, Yi,Zhou, Xue,Yang, Wengang,Wu, Jim Z.,Yang, Guang,Mayweg, Alexander V.,Shen, Hong C.,Tang, Guozhi
, p. 7651 - 7666 (2016/09/04)
Targeting the capsid protein of hepatitis B virus (HBV) and thus interrupting normal capsid formation have been an attractive approach to block the replication of HBV viruses. We carried out multidimensional structural optimizations based on the heteroaryldihydropyrimidine (HAP) analogue Bay41-4109 (1) and identified a novel series of HBV capsid inhibitors that demonstrated promising cellular selectivity indexes, metabolic stabilities, and in vitro safety profiles. Herein we disclose the design, synthesis, structureactivity relationship (SAR), cocrystal structure in complex with HBV capsid proteins and in vivo pharmacological study of the 4-methyl HAP analogues. In particular, the (2S,4S)-4,4-difluoroproline substituted analogue 34a demonstrated high oral bioavailability and liver exposure and achieved over 2 log viral load reduction in a hydrodynamic injected (HDI) HBV mouse model.
Discovery of novel cyanodihydropyridines as potent mineralocorticoid receptor antagonists
Arhancet, Graciela B.,Woodard, Scott S.,Iyanar, Kaliappan,Case, Brenda L.,Woerndle, Rhonda,Dietz, Jessica D.,Garland, Danny J.,Collins, Joe T.,Payne, Maria A.,Blinn, James R.,Pomposiello, Silvia I.,Hu, Xiao,Heron, Marcia I.,Huang, Horng-Chih,Lee, Len F.
experimental part, p. 5970 - 5978 (2010/11/02)
A new 1,4-dihydropyridine 5a, containing a cyano group at the C3 position, was recently reported to possess excellent mineralocorticoid receptor (MR) antagonist in vitro potency and no calcium channel-blocker (CCB) activity. In the present study, we report the structure-activity relationships of this novel series of cyano ester dihydropyridines that resulted in R6 substituted analogues with improved metabolic stability while maintaining excellent MR antagonist activity and selectivity against other nuclear receptors. Further structure optimization with the introduction of five-membered ring heterocycles at R6 resulted in compounds with excellent MR antagonist potency and a suitable pharmacokinetic profile. In vivo studies of a promising tool compound in the Dahl salt-sensitive rat model of hypertension showed similar blood pressure (BP) reduction as the steroidal MR antagonist eplerenone, providing proof-of-concept (POC) for a nonsteroidal, orally efficacious MR antagonist.
Medicaments against viral diseases
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Page 9, (2010/02/05)
Novel dihydropyrimidines and combinations thereof with other antiviral agents, suitable for combating HBV infections.
