药学学报, 2010, 45(5): 539-547
引用本文:
郭宗儒. 药物分子设计的策略:药理活性与成药性[J]. 药学学报, 2010, 45(5): 539-547.
GUO Zong-Ru. Strategy of molecular drug design: activity and druggability[J]. Acta Pharmaceutica Sinica, 2010, 45(5): 539-547.

药物分子设计的策略:药理活性与成药性
郭宗儒*
(中国医学科学院药物研究所, 北京 100050)
摘要:

化合物的内在活性和成药性是创新药物的两个基本要素, 活性是药物的基础和核心, 成药性是辅佐活性发挥药效的必要条件, 两者互为依存。药物在体内的药剂相、药代动力相和药效相可概括为活性和成药性的展示过程。成药性是药物除活性外的其他所有性质, 包括物理化学性质、生物化学性质、药代动力学性质和毒副作用, 这是在不同层次上表征药物的性质和行为, 但又相互关联与制约。活性与成药性由化学结构所决定, 体现在微观结构与宏观性质的结合上, 寓于分子的结构之中。先导物的优化是对活性、物化、生化、药代和安全性等性质的多维空间的分子操作, 因而具有丰富的药物化学内涵。

关键词:   
Strategy of molecular drug design: activity and druggability
Abstract:

Intrinsic activity and druggability represent two essences of innovative drugs.  Activity is the fundamental and core virtue of a drug, whereas druggability is essential to translate activity to therapeutic    usefulness.  Activity and druggability are interconnected natures residing in molecular structure.  The pharmaceutical, pharmacokinetic and pharmacodynamic phases in vivo can be conceived as an overall exhibition of   activity and druggability.  Druggability actually involves all properties, except for intrinsic activity, of a drug.  It embraces physico-chemical, bio-chemical, pharmacokinetic and toxicological characteristics, which are intertwined properties determining the attributes and behaviors of a drug in different aspects.  Activity and druggability of a drug are endowed in the chemical structure and reflected in the microscopic structure and macroscopic property of a drug molecule.  The lead optimization implicates molecular manipulation in multidimensional space covering activity, physicochemistry, biochemistry, pharmacokinetics and safety, and embodies abundant contents of medicinal chemistry.

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