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Translation of In Vitro Activity to In Vivo Activity: Lessons from the Triazolopyrimidine Sulfonanilides

Published online by Cambridge University Press:  12 June 2017

B. Clifford Gerwick ,
Csaba T. Cseke ,
Gerry Deboer ,
William A. Kleschick  and
Paul R. Schmitzer
B. Clifford Gerwick
Affiliation:
DowElanco, 9330 Zionsville Road, Indianapolis, IN 46268
Csaba T. Cseke
Affiliation:
DowElanco, 9330 Zionsville Road, Indianapolis, IN 46268
Gerry Deboer
Affiliation:
DowElanco, 9330 Zionsville Road, Indianapolis, IN 46268
William A. Kleschick
Affiliation:
DowElanco, 9330 Zionsville Road, Indianapolis, IN 46268
Paul R. Schmitzer
Affiliation:
DowElanco, 9330 Zionsville Road, Indianapolis, IN 46268
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Abstract

Eight triazolopyrimidine sulfonanilides were tested for metabolic stability in a number of crop and weed species. These data, along with in vitro determinations of activity (I50) against acetolactate synthase, successfully described the in vivo activity of these compounds in a two-parameter model. Whole plant activity increased with increasing compound stability and decreasing I50 (r2 =.78, N = 36). The difficulty in obtaining metabolic stability data during a structure optimization program prompted a study with substituent parameters in models of in vivo activity. Models describing whole plant activity in jimsonweed were developed using a series of 5-methyl triazolopyrimidine sulfonanilides that differed only in ortho and meta substituents on the aniline ring. The I50 term and clogP were most important to jimsonweed activity. Hence, in vitro activity (I50) may be a useful component of whole plant structure activity models to aid in identification of barriers to in vivo performance.

Keywords

jimsonweed, Datura stramonium L. ♯ DATSTAcetolactate synthaseacetohydroxyacid synthasequantitative structure activity relationships
Type
Symposium
Information
Weed Science , Volume 44 , Issue 3 , September 1996 , pp. 757 - 762
Copyright
Copyright © 1996 by the Weed Science Society of America 

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