Lead compound optimization strategy (4)--improving blood-brain barrier permeability through structural modification.
- Author:
Yu HONG
;
Yu ZHOU
;
Jiang WANG
;
Hong LIU
- Publication Type:Journal Article
- MeSH:
ATP-Binding Cassette, Sub-Family B, Member 1;
metabolism;
Biological Transport;
Blood-Brain Barrier;
Central Nervous System;
drug effects;
Central Nervous System Agents;
pharmacokinetics;
Drug Design;
Humans;
Permeability;
Xenobiotics;
adverse effects
- From:
Acta Pharmaceutica Sinica
2014;49(6):789-799
- CountryChina
- Language:Chinese
-
Abstract:
Blood-brain barrier is a natural protection for human body. It protects central nervous system from the interruption and damage of xenobiotics. However, it prevents potential drugs aimed at central nervous system, thus becomes an obstruction for the development of central nervous system drugs. The recent development of blood-brain barrier permeability research and several lead optimization strategies to improve blood-brain barrier permeability are reviewed. These structure optimization methods include increasing lipophilicity, reducing hydrogen bond doners, simplifying molecule, increasing rigidity, lowering polar surface area, avoiding acid group, prodrug strategy, modifying into active transporter's substrates, as well as avoiding P-glycoprotein recognized structures.
