Rationally Designing Safer Anilines: The Challenging Case of 4-Aminobiphenyls

详细信息    查看全文

• 作者：Alan M. Birch ; Sam Groombridge ; Robert Law ; Andrew G. Leach ; Christine D. Mee ; Carolin Schramm
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：April 26, 2012
• 年：2012
• 卷：55
• 期：8
• 页码：3923-3933
• 全文大小：660K
• 年卷期：v.55,no.8(April 26, 2012)
• ISSN：1520-4804

文摘

We describe how we have been able to design 4-aminobiphenyls that are nonmutagenic (inactive in the Ames test). No such 4-aminobiphenyls were known to us, but insights provided by quantum mechanical calculations have permitted us to design and synthesize some examples. Importantly, the quantum mechanical calculations could be combined with predictions of other properties of the compounds that contained the 4-aminobiphenyls so that these remained druglike. Having found compounds that are not active, the calculations can provide insight into which factors (electronic and conformational in this case) are important. The calculations provided SAR-like information that was able guide the design of further examples of 4-aminobiphenyls that are not active in the Ames test.