Medicinal chemistry of hERG optimizations: Highlights and hang-ups

被引:363
作者
Jamieson, Craig [1 ]
Moir, Elizabeth M. [1 ]
Rankovic, Zoran [1 ]
Wishart, Grant [1 ]
机构
[1] Organon Res Labs Ltd, Med Chem, Newhouse ML1 5SH, Lanark, Scotland
关键词
D O I
10.1021/jm060379l
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
[No abstract available]
引用
收藏
页码:5029 / 5046
页数:18
相关论文
共 71 条
[1]   MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia [J].
Abbott, GW ;
Sesti, F ;
Splawski, I ;
Buck, ME ;
Lehmann, WH ;
Timothy, KW ;
Keating, MT ;
Goldstein, SAN .
CELL, 1999, 97 (02) :175-187
[2]   Tetrahydronaphthalene-derived amino alcohols and amino ketones as potent and selective inhibitors of the delayed rectifier potassium current IKs [J].
Ahmad, S ;
Doweyko, L ;
Ashfaq, A ;
Ferrara, FN ;
Bisaha, SN ;
Schmidt, JB ;
DiMarco, J ;
Conder, ML ;
Jenkins-West, T ;
Normandin, DE ;
Russell, AD ;
Smith, MA ;
Levesque, PC ;
Lodge, NJ ;
Lloyd, J ;
Stein, PD ;
Atwal, KS .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (01) :99-102
[3]   Prediction of herg K+ blocking potency:: Application of structural knowledge [J].
Aptula, AO ;
Cronin, MTD .
SAR AND QSAR IN ENVIRONMENTAL RESEARCH, 2004, 15 (5-6) :399-411
[4]   A model for identifying HERG K+ channel blockers [J].
Aronov, AM ;
Goldman, BB .
BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (09) :2307-2315
[5]   Predictive in silico modeling for hERG channelblockers [J].
Aronov, MM .
DRUG DISCOVERY TODAY, 2005, 10 (02) :149-155
[6]   HERG binding specificity and binding site structure: evidence from a fragment-based evolutionary computing SAR study [J].
Bains, W ;
Basman, A ;
White, C .
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, 2004, 86 (02) :205-233
[7]   3-aminopyrrolidinone farnesyltransferase inhibitors: Design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency [J].
Bell, IM ;
Gallicchio, SN ;
Abrams, M ;
Beese, LS ;
Beshore, DC ;
Bhimnathwala, H ;
Bogusky, MJ ;
Buser, CA ;
Culberson, JC ;
Davide, J ;
Ellis-Hutchings, M ;
Fernandes, C ;
Gibbs, JB ;
Graham, SL ;
Hamilton, KA ;
Hartman, GD ;
Heimbrook, DC ;
Homnick, CF ;
Huber, HE ;
Huff, JR ;
Kassahun, K ;
Koblan, KS ;
Kohl, NE ;
Lobell, RB ;
Lynch, JJ ;
Robinson, R ;
Rodrigues, AD ;
Taylor, JS ;
Walsh, ES ;
Williams, TM ;
Zartman, CB .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (12) :2388-2409
[8]   Design and biological activity of (S)-4-(5-{[1-(3-chlorobenzyl)-2-oxopyrrolidin-3-ylamino]methyl}imidazol-1-ylmethyl)benzonitrile, a 3-aminopyrrolidinone farnesyltransferase inhibitor with excellent cell potency [J].
Bell, IM ;
Gallicchio, SN ;
Abrams, M ;
Beshore, DC ;
Buser, CA ;
Culberson, JC ;
Davide, J ;
Ellis-Hutchings, M ;
Fernandes, C ;
Gibbs, JB ;
Graham, SL ;
Hartman, GD ;
Heimbrook, DC ;
Homnick, CF ;
Huff, JR ;
Kassahun, K ;
Koblan, KS ;
Kohl, NE ;
Lobell, RB ;
Lynch, JJ ;
Miller, PA ;
Omer, CA ;
Rodrigues, AD ;
Walsh, ES ;
Williams, TM .
JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (18) :2933-2949
[9]   Potent N-(1,3-thiazol-2-yl)pyridin-2-amine vascular endothelial growth factor receptor tyrosine kinase inhibitors with excellent pharmacokinetics and low affinity for the hERG ion channel [J].
Bilodeau, MT ;
Balitza, AE ;
Koester, TJ ;
Manley, PJ ;
Rodman, LD ;
Buser-Doepner, C ;
Coll, KE ;
Fernandes, C ;
Gibbs, JB ;
Heimbrook, DC ;
Huckel, WR ;
Kohl, N ;
Lynch, JJ ;
Mao, XZ ;
McFall, RC ;
McLoughlin, D ;
Miller-Stein, CM ;
Rickert, KW ;
Sepp-Lorenzino, L ;
Shipman, JM ;
Subramanian, R ;
Thomas, KA ;
Wong, BK ;
Yu, S ;
Hartman, GD .
JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (25) :6363-6372
[10]  
*BIOB CORP, CLOGP VERS 4 10