Ionization, lipophilicity, and molecular modeling to investigate permeability and other biological properties of amlodipine

被引：30
作者：
Caron, G
Ermondi, G
Damiano, A
Novaroli, L
Tsinman, O
Ruell, JA
Avdeef, A
机构：
[1] Univ Turin, Dipartimento Sci & Technol Farmaco, I-10125 Turin, Italy
[2] pION Inc, Woburn, MA 01801 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2004年 / 12卷 / 23期
关键词：
isotropic lipophilicity; anisotropic lipophilicity; permeability; PAMPA; molecular dynamics simulation; ASA descriptors; intramolecular effects;
D O I：
10.1016/j.bmc.2004.09.004
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
This paper uses a recent approach toward drug discovery, in which in silico tools and experimental data are combined together to study the structural features of amlodipine and their relevance in the peculiar pharmacodynamic and pharmacokinetic profiles of this long acting calcium antagonist. Results reveal for amlodipine two families of conformers (folded and extended) but also demonstrate that protonation is-the predominant factor governing amlodipine intermolecular interactions among which ionic forces play a major role. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码：6107 / 6118
页数：12
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