Medicinal chemical properties of successful central nervous system drugs

被引：1121
作者：
Pajouhesh H. [1 ,3 ]
Lenz G.R. [2 ]
机构：
[1] Department of Medicinal Chemistry, Neuromed Technologies Inc., Vancouver
[2] GRLEN R and D Associates, Andover
[3] Neuromed Technologies Inc., 301-2389 Health Sciences Mall, Vancouver
来源：
NeuroRX | 2005年 / 2卷 / 4期
关键词：
ADME; (absorption; distribution; metabolism; and excretion); Blood-brain barrier (BBB); CNS drug; Pharmacokinetic properties; Physicochemical properties; QSAR;
D O I：
10.1602/neurorx.2.4.541
中图分类号：
学科分类号：
摘要：
Fundamental physiochemical features of CNS drugs are related to their ability to penetrate the blood-brain barrier affinity and exhibit CNS activity. Factors relevant to the success of CNS drugs are reviewed. CNS drugs show values of molecular weight, lipophilicity, and hydrogen bond donor and acceptor that in general have a smaller range than general therapeutics. Pharmacokinetic properties can be manipulated by the medicinal chemist to a significant extent. The solubility, permeability, metabolic stability, protein binding, and human ether-ago-go-related gene inhibition of CNS compounds need to be optimized simultaneously with potency, selectivity, and other biological parameters. The balance between optimizing the physiochemical and pharmacokinetic properties to make the best compromises in properties is critical for designing new drugs likely to penetrate the blood brain barrier and affect relevant biological systems. This review is intended as a guide to designing CNS therapeutic agents with better drug-like properties. © The American Society for Experimental NeuroTherapeutics, Inc.
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页码：541 / 553
页数：12
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