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Rationally designing safer anilines: the challenging case of 4-aminobiphenyls.

Authors
  • Birch, Alan M
  • Groombridge, Sam
  • Law, Robert
  • Leach, Andrew G
  • Mee, Christine D
  • Schramm, Carolin
Type
Published Article
Journal
Journal of Medicinal Chemistry
Publisher
American Chemical Society
Publication Date
Apr 26, 2012
Volume
55
Issue
8
Pages
3923–3933
Identifiers
DOI: 10.1021/jm3001295
PMID: 22475078
Source
Medline
License
Unknown

Abstract

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.

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