TY - JOUR
AU - Townson, S
AB - Transition state phosphoramidate inhibitors of β-tubulin were designed as potential antifilarial agents.The reactionof 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)amino-benzimidazole (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.
TI - Potential transition state phosphoramidate inhibitors of β-tubulin as antifilarial agents
JF - Journal of Pharmacy and Pharmacology
DO - 10.1211/0022357011775055
DA - 2001-01-01
UR - https://www.deepdyve.com/lp/oxford-university-press/potential-transition-state-phosphoramidate-inhibitors-of-tubulin-as-1Cp0xx2s8p
SP - 89
EP - 94
VL - 53
IS - 1
DP - DeepDyve
ER -