893643-33-9Relevant articles and documents
In Vitro Pharmacokinetic Optimizations of AM2-S31N Channel Blockers Led to the Discovery of Slow-Binding Inhibitors with Potent Antiviral Activity against Drug-Resistant Influenza A Viruses
Wang, Yuanxiang,Hu, Yanmei,Xu, Shuting,Zhang, Yongtao,Musharrafieh, Rami,Hau, Raymond Kin,Ma, Chunlong,Wang, Jun
, p. 1074 - 1085 (2018/02/17)
Influenza viruses are respiratory pathogens that are responsible for both seasonal influenza epidemics and occasional influenza pandemics. The narrow therapeutic window of oseltamivir, coupled with the emergence of drug resistance, calls for the next-generation of antivirals. With our continuous interest in developing AM2-S31N inhibitors as oral influenza antivirals, we report here the progress of optimizing the in vitro pharmacokinetic (PK) properties of AM2-S31N inhibitors. Several AM2-S31N inhibitors, including compound 10b, were discovered to have potent channel blockage, single to submicromolar antiviral activity, and favorable in vitro PK properties. The antiviral efficacy of compound 10b was also synergistic with oseltamivir carboxylate. Interestingly, binding kinetic studies (Kd, Kon, and Koff) revealed several AM2-S31N inhibitors that have similar Kd values but significantly different Kon and Koff values. Overall, this study identified a potent lead compound (10b) with improved in vitro PK properties that is suitable for the in vivo mouse model studies.
New pyrazole derivatives as CRAC channel modulators
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Paragraph 0101, (2015/03/28)
The present invention relates to compounds of formula (I) which are inhibitors of CRAC channel activity. This invention also relates to pharmaceutical compositions containing them, process for their preparation and their use in therapy.
PYRAZOLE DERIVATIVES AS S1P1 AGONISTS
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Page/Page column 57-58, (2011/12/04)
The present invention relates to a compound of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by sphingosine-1-phosphate receptors (S1P1) agonists.
New pyrazole derivatives
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Paragraph 0259; 0260, (2013/03/26)
The present invention relates to a compound of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by sphingosine-1-phosphate receptors (S1P1) agonists.