Pyrano-[2,3b]-pyridines as potassium channel antagonists
摘要:
The design and synthesis of a series of highly functionalized pyrano-[2,3b]-pyridines is described. These compounds were assayed for their ability to block the I-Kur channel encoded by the gene hKV1.5 in patch-clamped L-929 cells. Six of the compounds in this series showed sub-micromolar activity, the most potent being 4-(4-ethyl-benzenesulfonylamino)-3-hydroxy-2,2-dimethyl-3,4dihydro-2H-pyrano[2,3b]-pyridine-6-carboxylic acid ethyl-phenyl-amide with an IC50 of 378 nM. (C) 2008 Elsevier Ltd. All rights reserved.
The present invention relates to novel lipopeptide compounds. The invention also relates to pharmaceutical compositions of these compounds and methods of using these compounds as antibacterial compounds. The invention also relates to methods of producing these novel lipopeptide compounds and intermediates used in producing these compounds.
The invention provides novel compounds having the general formula:
and tautomers and pharmaceutically acceptable salts thereof, wherein A
1
, A
2
, A
3
, A
4
, R
1
, R
4
, R
5
, R
6
, R
7
and R
8
are as defined herein, compositions including the compounds and methods of using the compounds.
US7408025B2
申请人:——
公开号:US7408025B2
公开(公告)日:2008-08-05
Pyrano-[2,3b]-pyridines as potassium channel antagonists
作者:Heather J. Finlay、John Lloyd、Michael Nyman、Mary Lee Conder、Tonya West、Paul Levesque、Karnail Atwal
DOI:10.1016/j.bmcl.2008.03.026
日期:2008.4
The design and synthesis of a series of highly functionalized pyrano-[2,3b]-pyridines is described. These compounds were assayed for their ability to block the I-Kur channel encoded by the gene hKV1.5 in patch-clamped L-929 cells. Six of the compounds in this series showed sub-micromolar activity, the most potent being 4-(4-ethyl-benzenesulfonylamino)-3-hydroxy-2,2-dimethyl-3,4dihydro-2H-pyrano[2,3b]-pyridine-6-carboxylic acid ethyl-phenyl-amide with an IC50 of 378 nM. (C) 2008 Elsevier Ltd. All rights reserved.