Potassium channel openers: The case of BK channel activators

被引:18
作者
Nardi, A.
Calderone, V.
Olesen, S. -P.
机构
[1] NeuroSearch AS, Dept Chem, DK-2750 Ballerup, Denmark
[2] Univ Pisa, Dipartimento Psichiat Neurobiol Farmacol & Biotec, I-56126 Pisa, Italy
[3] Univ Copenhagen, Panum Inst, Dept Med Physiol, DK-2200 Copenhagen N, Denmark
[4] Danish Natl Res Fdn, Ctr Cardiac Arrhythmia Res, DK-2200 Copenhagen N, Denmark
[5] NeuroSearch AS, Dept Ion Channel Physiol, DK-2750 Ballerup, Denmark
关键词
potassium channels; BK-channels; Maxi-K channels; drug design; BK channel activator; synthesis;
D O I
10.2174/157018006776743242
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Large-conductance calcium-activated potassium channels, also known as BK or Maxi-K channels, occur in many types of cells, where they play an essential role in the regulation of cell excitability and function. BK channel openers constitute a heterogeneous group of organic compounds being able to activate BK channels and having a wide therapeutic potential for the treatment of different neurological, urological and cardiovascular diseases. This review addresses the novel research on BK channels as drug targets as well as it reports recent developments in the chemistry of BK channel openers and in the chemical structural aspects determining their activity.
引用
收藏
页码:210 / 218
页数:9
相关论文
共 120 条
[41]   Synthesis and structure-activity relationships of 3-aryloxindoles: A new class of calcium-dependent, large conductance potassium (maxi-K) channel openers with neuroprotective properties [J].
Hewawasam, P ;
Erway, M ;
Moon, SL ;
Knipe, J ;
Weiner, H ;
Boissard, CG ;
Post-Munson, DJ ;
Gao, Q ;
Huang, S ;
Gribkoff, VK ;
Meanwell, NA .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (07) :1487-1499
[42]   Discovery of a novel class of BK channel openers: Enantiospecific synthesis and BK channel opening activity of 3-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-3-hydroxy-6-(trifluoromethyl)-2H-indol-2-one [J].
Hewawasam, P ;
Meanwell, NA .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (10) :1255-1260
[43]   The synthesis and characterization of BMS-204352 (MaxiPost™) and related 3-fluorooxindoles as openers of maxi-K potassium channels [J].
Hewawasam, P ;
Gribkoff, VK ;
Pendri, Y ;
Dworetzky, SI ;
Meanwell, NA ;
Martinez, E ;
Boissard, CG ;
Post-Munson, DJ ;
Trojnacki, JT ;
Yeleswaram, K ;
Pajor, LM ;
Knipe, J ;
Gao, Q ;
Perrone, R ;
Starrett, JE .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (07) :1023-1026
[44]   The synthesis and structure-activity relationships of 4-aryl-3-aminoquinolin-2-ones: A new class of calcium-dependent, large conductance, potassium (maxi-K) channel openers targeted for post-stroke neuroprotection [J].
Hewawasam, P ;
Fan, WH ;
Knipe, J ;
Moon, SL ;
Boissard, CG ;
Gribkoff, VK ;
Starrett, JE .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (13) :1779-1783
[45]  
HEWAWASAM P, 1996, Patent No. 5565483
[46]   Effects of the BKCa channel activator, NS1619, on rat cerebral artery smooth muscle [J].
Holland, M ;
Langton, PD ;
Standen, NB ;
Boyle, JP .
BRITISH JOURNAL OF PHARMACOLOGY, 1996, 117 (01) :119-129
[47]  
Hongu M., 2002, PCT Int. Appl, Patent No. [WO2002/083111 A2 1-301, 2002083111]
[48]   Presynaptic Ca2+-activated K+ channels in glutamatergic hippocampal terminals and their role in spike repolarization and regulation of transmitter release [J].
Hu, H ;
Shao, LR ;
Chavoshy, S ;
Gu, N ;
Trieb, M ;
Behrens, R ;
Laake, P ;
Pongs, O ;
Knaus, HG ;
Ottersen, OP ;
Storm, JF .
JOURNAL OF NEUROSCIENCE, 2001, 21 (24) :9585-9597
[49]  
Hu SL, 1997, DRUG DEVELOP RES, V41, P10, DOI 10.1002/(SICI)1098-2299(199705)41:1<10::AID-DDR2>3.0.CO
[50]  
2-V