Discovery of azabenzimidazole derivatives as potent, selective inhibitors of TBK1/IKKε kinases

Wang, Tao; Block, Michael H.; Cowen, Scott D.; Davies, Audrey M.; Devereaux, Erik; Gingipalli, Lakshmaiah; Johannes, Jeffrey W.; Larsen, Nicholas; Su, Qibin; Tucker, J.A.; Whitston, David; Wu, Joy T.; Zhang, Haijun; Zinda, Michael; Chuaqui, Claudio

doi:10.1016/j.bmcl.2012.01.018

Cited by 44 publications

(37 citation statements)

References 13 publications

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“…Patents (2015) 25 (12) continued to explore TBK1 inhibitors [34]. They modified the structure of BX795 and generated the improved compound MRT67307 (Figure 2), which exhibited highly effective and selective TBK1 inhibition [35]. The IC 50 values of MRT67307 were 160 and 19 nM against IKK" and TBK1, respectively, and this compound lacked inhibition of IKKa and IKKb even at 10 µM.…”

Section: Tbk1 Inhibitorsmentioning

confidence: 99%

“…The IC 50 of several compounds in the series reached a concentration of 10 nM [35]. The structures of these compounds are shown in Figure 3.…”

Section: Astrazenecamentioning

confidence: 99%

“…Johannes et al at AstraZeneca developed an additional 35 compounds with 6-aryl-azabenzimidazole derivatives [35]. They focused on screening the 6-substituted azabenzimidazoles against TBK1 and identified a series of potential effective inhibitors, including compound 15 that pairs a C6 aryl group with a C7-nitrogen linkage via the introduction of a thiazole group.…”

Section: Astrazenecamentioning

confidence: 99%

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TBK1 inhibitors: a review of patent literature (2011 – 2014)

Yang

Yin

et al. 2015

Expert Opinion on Therapeutic Patents

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The role of TBK1 in various diseases has prompted the further investigation of significant targets. Although research on TBK1 inhibitors has increased over the last few years, only a few inhibitors of this kinase have been identified. In addition, almost all of the chemical inhibitors are modified from different scaffolds and/or chemotypes of pyrimidine. Specifically, compound BX795 is the representative one, which was first patented as a potent TBK1 inhibitor. Even though some compounds have displayed interesting potential inhibition and selectivity of TBK1 in vitro and in in vivo trials, the development of more efficient and selective TBK1 inhibitors is still required.

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Section: Tbk1 Inhibitorsmentioning

confidence: 99%

“…The IC 50 of several compounds in the series reached a concentration of 10 nM [35]. The structures of these compounds are shown in Figure 3.…”

Section: Astrazenecamentioning

confidence: 99%

Section: Astrazenecamentioning

confidence: 99%

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TBK1 inhibitors: a review of patent literature (2011 – 2014)

Yang

Yin

et al. 2015

Expert Opinion on Therapeutic Patents

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“…optimization [66]. The compound is potent and selective vs. other kinases, and is active in cellular assays.…”

Section: P62mentioning

confidence: 99%

Targeting Selective Autophagy of Insoluble Protein Aggregates

Seneci

2015

Chemical Modulators of Protein Misfolding and Neurodegenerative Disease

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“…Scaffold of compound 1 was known in various documents. [30][31][32] Based on the structure of compound 1, the rational design of a potent Tyk2 inhibitor was performed. To obtain the extended structure of compound 1 available at the active site of Tyk2, we conducted the following series of SAR studies by comparing docking models.…”

mentioning

confidence: 99%