Structure–activity relationship and liver microsome stability studies of pyrrole necroptosis inhibitors
| dc.contributor.author | Teng, Xin | |
| dc.contributor.author | Keys, Heather | |
| dc.contributor.author | Yuan, Junying | |
| dc.contributor.author | Degterev, Alexei | |
| dc.contributor.author | Cuny, Gregory D. | |
| dc.date.accessioned | 2020-03-10T17:32:24Z | |
| dc.date.available | 2020-03-10T17:32:24Z | |
| dc.date.issued | 2009-06 | |
| dc.description.abstract | Necroptosis is a regulated caspase-independent cell death pathway resulting in morphology reminiscent of passive non-regulated necrosis. Several diverse structure classes of necroptosis inhibitors have been reported to date, including a series of [1,2,3]thiadiazole benzylamide derivatives. However, initial evaluation of mouse liver microsome stability indicated that this series of compounds was rapidly degraded. A structure–activity relationship (SAR) study of the [1,2,3]thiadiazole benzylamide series revealed that increased mouse liver microsome stability and increased necroptosis inhibitory activity could be accomplished by replacement of the 4-cyclopropyl-[1,2,3]thiadiazole with a 5-cyano-1-methylpyrrole. In addition, the SAR and the cellular activity profiles, utilizing different cell types and necroptosis-inducing stimuli, of representative [1,2,3]thiadiazole and pyrrole derivatives were very similar suggesting that the two compound series inhibit necroptosis in the same manner. | |
| dc.identifier.citation | Copyright 2008 Bioorganic and Medicinal Chemistry Letters. This is is a post-print version of a published paper that is available at: https://www.sciencedirect.com/science/article/pii/S0960894X08004484.Recommended citation: Teng, Xin, Heather Keys, Junying Yuan, Alexei Degterev, and Gregory D. Cuny. "Structure–activity relationship and liver microsome stability studies of pyrrole necroptosis inhibitors." Bioorganic & medicinal chemistry letters 18, no. 11 (2008): 3219-3223. doi: 10.1016/j.bmcl.2008.04.048. This item has been deposited in accordance with publisher copyright and licensing terms and with the author's permission. | |
| dc.identifier.uri | https://hdl.handle.net/10657/5980 | |
| dc.language.iso | en_US | |
| dc.publisher | Bioorganic and Medicinal Chemistry Letters | |
| dc.subject | Cell death | |
| dc.subject | Necrosis | |
| dc.subject | Necroptosis | |
| dc.subject | Microsome stability | |
| dc.subject | Caspase-independent | |
| dc.subject | Pyrroles | |
| dc.subject | SAR | |
| dc.title | Structure–activity relationship and liver microsome stability studies of pyrrole necroptosis inhibitors | |
| dc.type | Article |