Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Racemic Descriptors for Quantitative Structure Activity Relationship of Spirosuccinimide Type Aldose Reductase Inhibitors

  • Kim, Jeong-Rim (Department of Applied Chemistry and Chemistry, Hanyang University) ;
  • Won, Young-Do (Department of Chemistry, Hanyang University)
  • Published : 2004.12.20
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Abstract

Quantitative structure activity relationship has been probed for spirosuccinimide-fused tetrahydropyrrolo[1,2-a]pyrazine-1,3-dione derivatives acting as aldose reductase inhibitors. While the spirosuccinimide compounds contain a chiral center, the aldose reductase inhibition assay was performed with racemic mixtures in the published work. As the physicochemical descriptors of the QSAR analysis must be evaluated for a definite molecular structure, we devise a new 'racemic' descriptor as the arithmetic mean of the (R)-enantiomer descriptor and the (S)-enantiomer descriptor. The resultant QSAR model derived from the racemic descriptors outperforms the original QSAR models, closely reproducing the observed activity of optically pure enantiomers as well as racemic mixtures.

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  1. 1-(Trifluoromethyl)-3,4-dihydropyrrolo-[1,2-a] pyrazines: synthesis and reactions with O- and N-nucleophiles vol.46, pp.10, 2011, https://doi.org/10.1007/s10593-011-0663-x
  2. Physical Chemistry Research Articles Published in the Bulletin of the Korean Chemical Society: 2003-2007 vol.29, pp.2, 2008, https://doi.org/10.5012/bkcs.2008.29.2.450