Synthesis and optimization of 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one based inhibitors of human neutrophil elastase.

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.

journal_name

Bioorg Med Chem Lett

authors

Shreder KR,Cajica J,Du L,Fraser A,Hu Y,Kohno Y,Lin EC,Liu SJ,Okerberg E,Pham L,Wu J,Kozarich JW

doi

10.1016/j.bmcl.2009.06.053

subject

Has Abstract

pub_date

2009-08-15 00:00:00

pages

4743-6

issue

16

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)00886-5

journal_volume

19

pub_type

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