Enantiomeric effects of homologues of disoxaril on the inhibitory activity against human rhinovirus-14

Guy D. Diana, Michael J. Otto, Adi M. Treasurywala, Mark A. McKinlay, Richard C. Oglesby, Edward G. Maliski, Michael G. Rossmann, Thomas Smith

Research output: Contribution to journalArticle

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Abstract

X-ray crystallography studies of racemic 5-[7-[4-(4,5-dihydro-4-methyl-2-oxazolyl)phenoxy]heptyl]-3-methylisoxazole (2) bound to human rhinovirus-14 (HRV-14) indicate selective binding of the S isomer. This result correlates well with the 10-fold greater activity of the S isomer as compared to the R isomer. The enantiomeric effect on activity is explained by a hydrophobic interaction of the methyl group in the case of 2a, with a pocket formed by Leu106 and Ser107. The 4-ethyl, 4-propyl, and 4-butyloxazolinyl homologues were prepared and tested against HRV-14. All of these compounds exhibited a comparable stereochemical effect. In each case, the S isomer displayed greater levels of activity than the R. The results of energetic considerations of the oxazoline ring in an 8-Å pocket bound to the HRV-14 binding site suggest that the twist angle between the oxazoline and phenyl rings resulting from hydrophobic interactions of the alkyl substituents could be one of the determining factors for biological activity.

Original languageEnglish (US)
Pages (from-to)540-544
Number of pages5
JournalJournal of Medicinal Chemistry
Volume31
Issue number3
StatePublished - 1988
Externally publishedYes

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Rhinovirus
Human Activities
Isomers
Hydrophobic and Hydrophilic Interactions
X Ray Crystallography
Biological Factors
X ray crystallography
Bioactivity
Binding Sites
disoxaril

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Diana, G. D., Otto, M. J., Treasurywala, A. M., McKinlay, M. A., Oglesby, R. C., Maliski, E. G., ... Smith, T. (1988). Enantiomeric effects of homologues of disoxaril on the inhibitory activity against human rhinovirus-14. Journal of Medicinal Chemistry, 31(3), 540-544.

Enantiomeric effects of homologues of disoxaril on the inhibitory activity against human rhinovirus-14. / Diana, Guy D.; Otto, Michael J.; Treasurywala, Adi M.; McKinlay, Mark A.; Oglesby, Richard C.; Maliski, Edward G.; Rossmann, Michael G.; Smith, Thomas.

In: Journal of Medicinal Chemistry, Vol. 31, No. 3, 1988, p. 540-544.

Research output: Contribution to journalArticle

Diana, GD, Otto, MJ, Treasurywala, AM, McKinlay, MA, Oglesby, RC, Maliski, EG, Rossmann, MG & Smith, T 1988, 'Enantiomeric effects of homologues of disoxaril on the inhibitory activity against human rhinovirus-14', Journal of Medicinal Chemistry, vol. 31, no. 3, pp. 540-544.
Diana GD, Otto MJ, Treasurywala AM, McKinlay MA, Oglesby RC, Maliski EG et al. Enantiomeric effects of homologues of disoxaril on the inhibitory activity against human rhinovirus-14. Journal of Medicinal Chemistry. 1988;31(3):540-544.
Diana, Guy D. ; Otto, Michael J. ; Treasurywala, Adi M. ; McKinlay, Mark A. ; Oglesby, Richard C. ; Maliski, Edward G. ; Rossmann, Michael G. ; Smith, Thomas. / Enantiomeric effects of homologues of disoxaril on the inhibitory activity against human rhinovirus-14. In: Journal of Medicinal Chemistry. 1988 ; Vol. 31, No. 3. pp. 540-544.
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