24小时热门版块排行榜

返回列表

1949stone

荣誉版主 (知名作家)

海纳百川

应助: 95 (初中生)
贵宾: 2.38
金币: 2602.9
散金: 3394
红花: 177
沙发: 8
帖子: 9825
在线: 2692.8小时
虫号: 765987
注册: 2009-05-08
性别: GG
专业: 药物分析
管辖: 分子生物

[交流] Bioisosteres in Medicinal Chemistry 已有3人参与

Bioisosteric replacement of substituents, ring atoms, linkers, and other groups aims
to generate chemical substitutes with related biological properties, in the hope that
the new analogues may have somewhat better properties. Such replacements are the
toolbox of medicinal chemists to optimize their lead structures with respect to
lipophilicity, solubility, activity, selectivity, absorption, metabolism, and lack of toxic
and other side effects. Whenever an analogue with some improved properties is
observed, the new compound is taken as the starting point for further modiﬁcation.
In this evolutionary procedure, either a preclinical or a clinical candidate results or
the project has to be terminated, without success. Whereas the whole process quite
often follows a trial and error procedure, certain empirical rules developed in
medicinal chemistry. Very simple ones are, for example, the replacement of a
hydrogen atom in the para-position of a benzene ring, to avoid rapid metabolic
degradation, or, on the other hand, the introduction of an aromatic methyl group
instead of a chlorine atom, to avoid too long biological half-life. More sophisticated
rules exist for modiﬁcation of the ligands of certain targets, for example, proteases or
kinases.
The organization of this book follows a logical sequence, starting with Part One on
the principles of bioisosterism, including an introductory chapter, and chapters on
classical bioisosteres in medicinal chemistry and the logical but often surprising
consequences of bioisosteric replacement. Part Two presents a database on bioisosteres
and bioanalogues and discusses the search for bioisosteres, using the Cambridge
Structure Database of 3D structures of small molecules, as well as the mining
of bioisosteric pairs. Part Three presents methods to identify bioisosteres under the
aspect of physicochemical properties, molecular topology, molecular shape, and
protein 3D structures. Part Four describes a computer program for drug design,
using medicinal chemistry rules, discusses the bioisosteric modiﬁcation of a receptor
antagonist, and ends with a concluding chapter on perspectives from medicinal
chemistry.
Whereas some reviews on bioisosteres are found in the literature, as well as
chapters in medicinal chemistry books, no dedicated monograph on bioisosteres has
been published so far. Thus, we are very grateful to Nathan Brown for editing such a
book, which will help novices in the ﬁeld as well as experienced scientists to manage
lead structure optimization in an even more rational manner. In addition, we are
very much indebted to Frank Weinreich and Heike Nöthe, both at Wiley-VCH. Their
support and ongoing engagement, not only for this book but also for the whole series
‘‘Methods and Principles in Medicinal Chemistry,’’ adds to the success of this
excellent collection of monographs on various topics, all related to drug research.

回复此楼