.png){kind=icon}
返回
Predicting properties and tuning physicochemical in lead optimization:: Amine basicities
.png){kind=icon}
PRE
AI
DOI：10.1002/cmdc.200700059.png)
.png){kind=icon}
原文求助.png){kind=icon}
分享.png){kind=icon}
收藏
摘要
En 中文
This review describes simple and useful concepts for predicting and tuning the pK(a), values of basic amine centers, a crucial step in the optimization of physical and ADME properties of many lead structures in drug-discovery research. The article starts with a case study of tricyclic thrombin inhibitors featuring a tertiary amine center with pK(a) values that con be tuned over a wide range, from the usual value of around 10 to below 2 by (remote) neighboring functionalities commonly encountered in medicinal chemistry. Next, the changes in pK(a) of acyclic and cyclic amines upon substitution by fluorine, oxygen, nitrogen, and sulfur functionalities, as well as carbonyl and corboxyl derivatives are systematically analyzed, leading to the derivation of simple rules for pK(a) prediction. Electronic and stereoelectronic effects in cyclic amines are discussed, and the emerging computational methods for pK(a) predictions are briefly surveyed. The rules for tuning amine basicities should not only be of interest in drug-discovery research, but also to the development of new crop-protection agents, new amine ligands for organometallic complexes, and in particular, to the growing field of amine-based orgonocatalysis.
Keyword:
CHIRAL N,N-DISUBSTITUTED TRIFLUORO-3-AMINO-2-PROPANOLS
FLUORINE SCAN
C-F
MULTIPOLAR INTERACTIONS
THROMBIN INHIBITORS
POTENT INHIBITORS
PK(A) VALUES
DISCOVERY
CHEMISTRY
AI总结
对已上传原文的论文进行重点信息的提取，主要内容包括：简要概述、研究摘要、背景介绍、关键亮点、图文解析、展望与总结。
期刊
IF:
3.4
论文数:
5.1K
被引数:
1.0W
机构
暂无机构信息
引用论文
.png){kind=icon}
分享收藏分享收藏
查看更多内容