Potential transition state phosphoramidate inhibitors of β-tubulin as antifilarial agents

R. J. Anderson, D. J. Bendell, M. Hooper, D. Cairns, S. P. Mackay, S. P. Hiremath, A. S. Jivanagi, S. Badami, J. S. Biradar, S. Townson

Research output: Contribution to journalArticle

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Abstract

Transition state phosphoramidate inhibitors of β-tubulin were designed as potential antifilarial agents. The reaction of 2-aminobenzimidazole with diisopropyl phosphite and carbon tetrachloride at a low temperature gave the unexpected 1-diisopropoxyphosphoryl-2-aminobenzimidazole, which on heating gave the novel benzimidazole derivative, 2-(diisopropoxyphosphoryl)-aminobenzimidazole. Both products were fully characterized and the synthetic procedure to both compounds was optimized. The procedure was used to prepare the related 5-benzoyl-2-(diisopropoxyphosphoryl)aminobenzimidazole and 5-benzoyl-2-(diethoxyphosphoryl)aminobenzimidazole (1d). In a preliminary trial against Brugia pahangi compound 1d was found to have no antifilarial activity. This lack of activity may be attributed to its extreme insolubility and thus low bioavailability. The synthesis of analogous, more soluble, phosphorothioate-substituted benzimidazoles using the same methods may yield compounds with greater antifilarial activity.

Original languageEnglish
Pages (from-to)89-94
Number of pages6
JournalJournal of Pharmacy and Pharmacology
Volume53
Issue number1
DOIs
Publication statusPublished - 31 Jan 2001

Fingerprint

Tubulin Modulators
Brugia pahangi
Benzimidazoles
Phosphites
Carbon Tetrachloride
Heating
Biological Availability
phosphoramidic acid
2-aminobenzimidazole
Temperature

Keywords

  • inhibitors
  • ynthetic procedure
  • antifilarial activity

Cite this

Anderson, R. J. ; Bendell, D. J. ; Hooper, M. ; Cairns, D. ; Mackay, S. P. ; Hiremath, S. P. ; Jivanagi, A. S. ; Badami, S. ; Biradar, J. S. ; Townson, S. / Potential transition state phosphoramidate inhibitors of β-tubulin as antifilarial agents. In: Journal of Pharmacy and Pharmacology. 2001 ; Vol. 53, No. 1. pp. 89-94.
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abstract = "Transition state phosphoramidate inhibitors of β-tubulin were designed as potential antifilarial agents. The reaction of 2-aminobenzimidazole with diisopropyl phosphite and carbon tetrachloride at a low temperature gave the unexpected 1-diisopropoxyphosphoryl-2-aminobenzimidazole, which on heating gave the novel benzimidazole derivative, 2-(diisopropoxyphosphoryl)-aminobenzimidazole. Both products were fully characterized and the synthetic procedure to both compounds was optimized. The procedure was used to prepare the related 5-benzoyl-2-(diisopropoxyphosphoryl)aminobenzimidazole and 5-benzoyl-2-(diethoxyphosphoryl)aminobenzimidazole (1d). In a preliminary trial against Brugia pahangi compound 1d was found to have no antifilarial activity. This lack of activity may be attributed to its extreme insolubility and thus low bioavailability. The synthesis of analogous, more soluble, phosphorothioate-substituted benzimidazoles using the same methods may yield compounds with greater antifilarial activity.",
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Anderson, RJ, Bendell, DJ, Hooper, M, Cairns, D, Mackay, SP, Hiremath, SP, Jivanagi, AS, Badami, S, Biradar, JS & Townson, S 2001, 'Potential transition state phosphoramidate inhibitors of β-tubulin as antifilarial agents', Journal of Pharmacy and Pharmacology, vol. 53, no. 1, pp. 89-94. https://doi.org/10.1211/0022357011775055

Potential transition state phosphoramidate inhibitors of β-tubulin as antifilarial agents. / Anderson, R. J.; Bendell, D. J.; Hooper, M.; Cairns, D.; Mackay, S. P.; Hiremath, S. P.; Jivanagi, A. S.; Badami, S.; Biradar, J. S.; Townson, S.

In: Journal of Pharmacy and Pharmacology, Vol. 53, No. 1, 31.01.2001, p. 89-94.

Research output: Contribution to journalArticle

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AU - Hiremath, S. P.

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AU - Biradar, J. S.

AU - Townson, S.

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