406728-81-2Relevant academic research and scientific papers
Identification of indole scaffold-based dual inhibitors of NOD1 and NOD2
Ke?ek Ple?ec, Kaja,Urban?i?, Dunja,Gobec, Martina,Peko?ak, Aleksandra,Toma?i?, Tihomir,Anderluh, Marko,Mlinari?-Ra??an, Irena,Jakopin, ?iga
, p. 5221 - 5234 (2016/10/24)
NOD1 and NOD2 are important members of the pattern recognition receptor family and play a crucial role within the context of innate immunity. However, overactivation of NODs, especially of NOD1, has also been implicated in a number of diseases. Surprisingly, NOD1 remains a virtually unexploited target in this respect. To gain additional insight into the structure–activity relationships of NOD1 inhibitors, a series of novel analogs has been designed and synthesized and then screened for their NOD1-inhibitory activity. Selected compounds were also investigated for their NOD2-inhibitory activity. Two compounds 4 and 15, were identified as potent mixed inhibitors of NOD1 and NOD2, displaying a balanced inhibitory activity on both targets in the low micromolar range. The results obtained have enabled a deeper understanding of the structural requirements for NOD1 and NOD2 inhibition.
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.
ARBOVIRUS INHIBITORS AND USES THEREOF
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, (2012/10/08)
The present invention relates to chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides compounds as inhibitors of arboviruses.
Aromatic derivatives with HIV integrase inhibitory properties
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, (2008/06/13)
A compound of formula I′ and pharmaceutically acceptable derivatives thereof including, for example, where applicable or appropriate pharmaceutically acceptable salts thereof. Ar and Ar′ are aromatic or aryl type groups. The compounds have HIV integrase inhibitory properties. Ar, Ar′ and W may be as defined in the specification.
Syntheses and biological evaluation of indole-2 and 3-carboxamides: New selective cyclooxygenase-2 inhibitors
Oelgen, Suereyya,Guener,Fabregat,Crespo,Nebioglu
, p. 238 - 242 (2007/10/03)
A series of indol-2 and 3-carboxamides were prepared and evaluated for their ability to inhibit cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1). Substitution on indol nitrogen with benzyl and p-fluorobenzyl group of indole-2 carboxamides 8, 10, 11 provides fairly active COX-2 enzyme inhibitors.
