915230-14-7Relevant academic research and scientific papers
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
supporting information, 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.
Aurora Kinase Modulators and Method of Use
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, (2014/11/27)
The present invention relates to chemical compounds having a general formula I wherein A1-8, D′, L1, L2, R1, R6-8 and n are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of such kinases. For example, the compounds are capable of modulating Aurora kinase thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of Aurora kinase.
PHENYL-3-{ (3- (1H- PYRROL- 2 -YL) - [1 , 2 , 4] 0XADIAZ0L-5-YL] PIPERIDIN-1-YL}-METHANONE DERIVATIVES AND RELATED COMPOUNDS AS POSITIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
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Page/Page column 71, (2008/06/13)
The present invention provides new compounds of formula (I) as positive allosteric modulators of metabotropic receptors - subtype 5 ("mGluR5") which are useful for the treatment or prevention of central nervous system disorders such as for example, cognitive decline, both positive and negative symptoms in schizophrenia as well as other central or peripheral nervous system disorders in which the mGluR5 subtype of glutamate metabotropic receptor is involved. The invention is also directed to pharmaceutical compounds and compositions in the prevention or treatment of such diseases in which mGluKi is involved. W represents (C4-C7)cycloalkyl, (C3-C7)heterocycloalkyl , (C3-C7)heterocycloalkyl-(C1-C3)alkyl or (C3-C7)heterocycloalkenyl ring; represents a (C5-C7)heteroeycloalkyl, (C5-C7)heterocycloalkeiiyl ring or a heteroaryl group of formula (a), (b), (c), (d), (e), (f), (g), (i). Q denotes a cycloalkyl, an aryl or heteroaryl group of formula (j), (k), (l), (m), (n). A is azo -N=N-, ethyl, ethenyl, ethynyl, -NR8C(=O)-, -NR8C(=O)-O-, -NR8C(=O)-NR9, NR8S(=O)2-, -C(=O)NR8-, -O-C(=O)NR8-, -S-, -S(=O)-, -S(=O)2-, -S(C=O)2NR8-, -C(=0)-0-, -0-C(=0)-, -C(=NR8)NR9-, C(C=NOR8)NR9- , -NR8C(=NOR9)-, =N-0-, -0-N=CH- or a group aryl or heteroaryl of formula, (o), (p), (q), (r), (s), (t), (u), (v), (w), (x). The other substituents are defined in the claims.
