Conformationally Restricted Analogues of Disoxaril: A Comparison of the Activity against Human Rhinovirus Types 14 and 1A

John P. Mallamo, Guy D. Diana, Daniel C. Pevear, Frank J. Dutko, Michael S. Chapman, Kyung H. Kim, Iwona Minor, Marcos Oliveira, Michael G. Rossmann

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

A series of conformationally restricted analogs of disoxaril has been synthesized and evaluated against human rhinovirus types (HRV) 14 and 1A. The sensitivity of these serotypes to this series varied and was dependent upon the length of the molecule as well as upon the flexibility of the aliphatic chain. Minimum energy conformations of these compounds were overlaid with the X-ray structure of a closely related analog 9 bound to the capsid protein of both HRV-14 and -1A and then modeled in the compound-binding site of both serotypes. A comparative sweep volume of these compounds about the isoxazole ring revealed an inaccessible region of space for the cis-olefin 8b, which is not the case for either the trans-olefin 8a or the acetylene 5. This region may be important to the binding of the compounds to the HRV-14 site particularly during entry into the pocket.

Original languageEnglish (US)
Pages (from-to)4690-4695
Number of pages6
JournalJournal of Medicinal Chemistry
Volume35
Issue number25
DOIs
StatePublished - Dec 1 1992

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Mallamo, J. P., Diana, G. D., Pevear, D. C., Dutko, F. J., Chapman, M. S., Kim, K. H., Minor, I., Oliveira, M., & Rossmann, M. G. (1992). Conformationally Restricted Analogues of Disoxaril: A Comparison of the Activity against Human Rhinovirus Types 14 and 1A. Journal of Medicinal Chemistry, 35(25), 4690-4695. https://doi.org/10.1021/jm00103a006