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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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References

Literature Cited

1. Brown, H. M. 1990. Mode of action, crop selectivity, and soil relations of the sulfonylurea herbicides. Pest. Sci. 29: 263–281.Google Scholar
2. Brown, H. M., Dietrick, R. F., Kenyon, W. H., and Lichtner, F. T. 1991. Prospects for the biorational design of crop selective herbicides. Pages 847–856 in Brighton Crop Protection Conference—Weeds.Google Scholar
3. Brown, H. M., Fuester, T. P., Ray, T. B., and Strackan, S. D. 1991. Role of plant metabolism in crop selectivity of herbicides. Pages 257–266 in Frehse, H. (ed.), Pesticide Chemistry XIV, Weinheim, Germany.Google Scholar
4. Chang, M., Brown, S. M., Swisher, B. A., DeBoer, G. J., Zabett, D., McKendry, L. H., Roth, G. A., Stanga, M. A., and Eilers, R. J. 1992. Comparative metabolism of flumetsulam (DE-498) in soybeans and lambsquarters. Abstr. Agro. 30, 204th ACS National Meeting.Google Scholar
5. Costales, M. J., Kleschick, W. A., and Gerwick, B. C. 1992. N (substituted-2-fluorophenyl) and -N-(substituted-2-trifluoromelhylphenyl)-1,2,4-triazolo [1,5-a] pyrimidine-2-sulfonanilides. Pages 26–33 in Synthesis and Chemistry of Agrochemicals III; Baker, D. R., Fenyes, J., Steffens, J. J., eds. ACS Symposium Series 504. American Chemical Society: Washington, D.C. Google Scholar
6. Cseke, C. T. 1994. Impact of inhibition kinetics on whole plant activity. Herbicide Physiology Workshop on “Target site interactions,” 8th IUPAC International Congress of Pesticide Chemistry, Washington, D.C. Google Scholar
7. Dumas, R., Cornillon-Bertrands, C., Guigue-Talet, P., Genix, P., Douce, R., and Job, D. 1994. Interactions of plant acetohydroxy acid isomerase with reaction intermediate analogues: correlation of the slow, competitive, inhibition kinetics of enzyme activity and herbicidal effects. Biochem. J. 301: 813–820.Google Scholar
8. Gerwick, B. C., Subramanian, M. V., Loney-Gallant, V. I., and Chandler, D. P. 1990. Mechanism of action of the 1,2,4-triazolo[1,5-a] pyrimidines. Pest. Sci. 29: 357–364.Google Scholar
9. Gerwick, B. C., DeBoer, G. J., and Schmitzer, P. R. 1995. Mechanisms of tolerance to triazolopyrimidine sulfonanilide herbicides. Pages 145–160 in Chemistry of plant protection. Herbicides inhibiting branched chain amino acid biosynthesis—newer developments. Springer-Verlag, Heidelburg.Google Scholar
10. Hansch, C. and Leo, A. 1979. Substituent constants for correlation analysis in chemistry and biology. John Wiley & Sons, New York.Google Scholar
11. Hodges, C. C., DeBoer, G. J., and Avalos, J. 1990. Uptake and metabolism as mechanisms of selective herbicidal activity of the 1,2,4-triazolo[1,5-a]pyrimidines. Pest. Sci. 29: 365–378.Google Scholar
12. Jachetta, J., VanHeertum, J. C., and Gerwick, B. C. 1995. Cloransulam—Methyl: A new herbicide for soybeans. WSSA (Abst.) 22.Google Scholar
13. Kleier, D. A. 1988. Phloem mobility of xenobiotics I. Mathematical model unifying the weak acid and intermediate permeability theories. Plant Physiol. 86: 803–810.Google Scholar
14. Kleschick, W. A. 1995. Triazolopyrimidine sulfonanilide herbicides and related compounds. Pages 119–144 in Chemistry of plant protection, herbicides inhibiting branched chain amino acid biosynthesis—newer developments. Springer-Verlag, Heidelburg.Google Scholar
15. Kleschick, W. A., Costales, M. J., Dunbar, J. E., Meikle, R. W., Monte, W. T., Pearson, N. R., Snider, S. W., and Vinogradoff, A. P. 1990. New herbicidal derivatives of 1,2,4-triazolo[1,5-a]pyrimidine. Pest. Sci. 29: 341–355.Google Scholar
16. Kleschick, W. A., Costales, M. J., Gerwick, B. C., Holtwick, J. B., Meikle, R. W., Monte, W. T., Pearson, N. R., Snider, S. W., Subramanian, M. V., VanHeertum, J. C., and Vinogradoff, A. P. 1992. 1,2,4-Triazolo[1,5-a]pyrimidine-2-sulfonanilide herbicides. The influence of alkyl, haloalkyl and haloheterocyclic substitution on the in vino and in vivo biological activity. Pages 10–16, in Baker, D. R., Fenyes, J., Steffens, J. J., Eds. Synthesis and Chemistry of Agrochemicals III; ACS Symposium Series 504, Amer. Chem. Soc.: Washington, D.C. Google Scholar
17. Kleschick, W. A., Carson, C. M., Costales, M. J., Doney, J. J., Gerwick, B. C., Holtwick, J. B., Little, J. C., Meikle, R. W., Monte, W. T., Pearson, N. R., Snider, S. W., Subramanian, M. V., VanHeertum, J. C., and Vinogradoff, A. P. 1992. 1,2,4-Triazolo[1,5-a]pyrimidine-2-sulfonanilide herbicides. The influence of alkoxy heterocyclic substitution on the in vitro and in vivo biological activity and soil decomposition. Pages 17–25 in Baker, D. R., Fenyes, J., Steffens, J. J., eds. Synthesis and Chemistry of Agrochemicals III; ACS Symposium Series 504, Amer. Chem. Soc.: Washington, D.C. Google Scholar
18. Kleschick, W. A., Gerwick, B. C., Carson, C. M., Monte, W. T., and Snider, S. W. 1992. DE-498: Anew acetolactate synthase inhibiting herbicide with multicrop selectivity. J. of Ag. Food Chem. 40: 1083–1085.Google Scholar
19. Ladner, D. W. 1990. Structure-activity relationships among the imidazolinone herbicides. Pest. Sci. 29: 317–334.Google Scholar
20. Lichtner, F. T. Phloem transport of agricultural chemicals. Pages 601–608 in Lucas, W. J., Cronshaw, J., eds. Proc. 3rd International Phloem Conference. (Asilomar, CA). Alan R. Liss Inc., New York.Google Scholar
21. Markley, L. D., Hamilton, C. T., Geselius, T. C., Swisher, B. A., and Secor, J. 1995. Synthesis and herbicidal activity of aryloxy and -pyridyloxy-phenyl cyclohexanedione grass herbicides. Pages 220–233 in Baker, D. R., Fenyes, J., Basarab, G., eds. Synthesis and Chemistry of Agrochemicals IV; ACS Symposium Series 584, Amer. Chem. Soc.: Washington, D.C. Google Scholar
22. Ridley, S. M. and McNally, S. F. 1985. Effects of phosphinothricin on the isoenzymes of glutamine synthatase isolated from plant species which exhibit varying degrees of susceptibility to the herbicide. Plant Sci. 39: 31–36.CrossRefGoogle Scholar
23. Westerfield, W. W. 1945. A colorimetric determination of blood acetoin. J. Biol. Chem. 161: 495–502.Google Scholar