924643-46-9Relevant academic research and scientific papers
Validation and Characterization of Five Distinct Novel Inhibitors of Human Cytomegalovirus
Kapoor, Arun,Ghosh, Ayan K.,Forman, Michael,Hu, Xin,Ye, Wenjuan,Southall, Noel,Marugan, Juan,Keyes, Robert F.,Smith, Brian C.,Meyers, David J.,Ferrer, Marc,Arav-Boger, Ravit
, p. 3896 - 3907 (2020)
The critical consequences of human cytomegalovirus (HCMV) infection in the transplant population and in congenitally infected infants, the limited treatment options for HCMV, and the rise of resistant mutants toward existing therapies has fueled the search for new anti-HCMV agents. A pp28-luciferase recombinant HCMV was used as a reporter system for high-throughput screening of HCMV inhibitors. Approximately 400"?000 compounds from existing libraries were screened. Subsequent validation assays using resynthesized compounds, several virus strains, and detailed virology assays resulted in the identification of five structurally unique and selective HCMV inhibitors, active at sub to low micromolar concentrations. Further characterization revealed that each compound inhibited a specific stage of HCMV replication. One compound was also active against herpes simplex virus (HSV1 and HSV2), and another compound was active against Epstein-Barr virus (EBV). Drug combination studies revealed that all five compounds were additive with ganciclovir or letermovir. Future studies will focus on optimization of these new anti-HCMV compounds along with mechanistic studies.
COMPOSITIONS FOR INHIBITION OF HERPESVIRUSES
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, (2021/07/31)
The disclosure herein provides compounds of formulas I-V which are useful in the inhibition of viral diseases in a subject. In some embodiments, the compounds of formulas I-V are useful in the inhibition of herpes viruses.
New sulfanilamide derivatives incorporating heterocyclic carboxamide moieties as carbonic anhydrase inhibitors
Angeli, Andrea,Brovarets, Volodymyr,Capasso, Clemente,De Luca, Viviana,Geronikaki, Athina,Kartsev, Victor,Panchishin, Svitlana Y.,Petrou, Anthi,Pinteala, Mariana,Supuran, Claudiu T.,Vydzhak, Roman M.
, (2021/08/31)
Carbonic Anhydrases (CAs) are ubiquitous metalloenzymes involved in several disease conditions. There are 15 human CA (hCA) isoforms and their high homology represents a challenge for the discovery of potential drugs devoid of off-target side effects. For this reason, many synthetic and pharmacologic research efforts are underway to achieve the full pharmacological potential of CA modulators of activity. We report here a novel series of sulfanilamide derivatives containing heterocyclic carboxamide moieties which were evaluated as CA inhibitors against the physiological relevant isoforms hCA I, II, IX, and XII. Some of them showed selectivity toward isoform hCA II and hCA XII. Molecular docking was performed for some of these compounds on isoforms hCA II and XII to understand the possible interaction with the active site amino acid residues, which rationalized the reported inhibitory activity.
Structural Optimizations of Thieno[3,2-b]pyrrole Derivatives for the Development of Metabolically Stable Inhibitors of Chikungunya Virus
Ching, Kuan-Chieh,Tran, Thi Ngoc Quy,Amrun, Siti Naqiah,Kam, Yiu-Wing,Ng, Lisa F. P.,Chai, Christina L. L.
supporting information, p. 3165 - 3186 (2017/04/21)
Chikungunya virus (CHIKV) is a re-emerging vector-borne alphavirus, and there is no approved effective antiviral treatment currently available for CHIKV. We previously reported the discovery of thieno[3,2-b]pyrrole 1b that displayed good antiviral activit
Novel inhibitors of neurotropic alphavirus replication that improve host survival in a mouse model of acute viral encephalitis
Sindac, Janice A.,Yestrepsky, Bryan D.,Barraza, Scott J.,Bolduc, Kyle L.,Blakely, Pennelope K.,Keep, Richard F.,Irani, David N.,Miller, David J.,Larsen, Scott D.
, p. 3535 - 3545 (2012/06/17)
Arboviral encephalitis is a potentially devastating human disease with no approved therapies that target virus replication. We previously discovered a novel class of thieno[3,2-b]pyrrole-based inhibitors active against neurotropic alphaviruses such as western equine encephalitis virus (WEEV) in cultured cells. In this report, we describe initial development of these novel antiviral compounds, including bioisosteric replacement of the 4H-thieno[3,2-b]pyrrole core with indole to improve metabolic stability and the introduction of chirality to assess target enantioselectivity. Selected modifications enhanced antiviral activity while maintaining low cytotoxicity, increased stability to microsomal metabolism, and also revealed striking enantiospecific activity in cultured cells. Furthermore, we demonstrate improved outcomes (both symptoms and survival) following treatment with indole analogue 9h (CCG-203926) in an in vivo mouse model of alphaviral encephalitis that closely correlate with the enantiospecific in vitro antiviral activity. These results represent a substantial advancement in the early preclinical development of a promising class of novel antiviral drugs against virulent neurotropic alphaviruses.
