期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 60, 期 9, 页码 3552-3579出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.6b01807
关键词
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There is a continued desire in biomedical research to reduce the number and duration of design cycles required to optimize lead compounds into high-quality chemical probes or safe and efficacious drug candidates. The insightful application of impactful molecular design elements is one approach toward achieving this goal. The replacement of a CH group with a N atom in aromatic and heteroaromatic ring systems can have many important effects on molecular and physicochemical properties and intra- and intermolecular interactions that can translate to improved pharmacological profiles. In this Perspective, the necessary nitrogen atom is shown to be a versatile high-impact design element for multiparameter optimization, wherein >= 10-, 100-, or 1000-fold improvement in a variety of key pharmacological parameters can be realized.
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