Synthesis and optimization of 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one based inhibitors of human neutrophil elastase. Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] Journal article | | Title | Synthesis and optimization of 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one based inhibitors of human neutrophil elastase. | | Author(s) | Shreder KR, Cajica J, Du L, Fraser A, Hu Y, Kohno Y, Lin EC, Liu SJ, Okerberg E, Pham L, Wu J, Kozarich JW | | Institution | ActivX Biosciences, Inc., 11025 N. Torrey Pines Road, La Jolla, CA 92037, USA. | | Source | Bioorg Med Chem Lett 2009 Jun 17. | | Abstract | The hit-to-lead optimization of the HNE inhibitor 5-methyl-2-(2-phenoxy-pyridin-3-yl)-benzo[d][1,3]oxazin-4-one is described. A structure-activity relationship study that focused on the 5 and 7 benzoxazinone positions yielded the optimized 5-ethyl-7-methoxy-benzo[d][1,3]oxazin-4-one core structure. 2-[2-(4-Methyl-piperazin-1-yl)-pyridin-3-yl] derivatives of this core were shown to yield HNE inhibitors of similar potency with significantly different stabilities in rat plasma. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19577470 |
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