Bioisostere of Sulfonyl Moiety-The Synthesis of New ALS Inhibitors N-(Asymmetry Disubstituted Phosphoryl)-N'-(4,6-dimethoxypyrimidin-2-yl) Ureas

In view of the isosterism of the sulfonyl (-SO2-) and phosphoryl groups [-P(O)(OR)-,R=H, CH3, C2H5, etc], two new types of ureas, N-(N-aryl-O-alkyl phosphoryl)-N'-(4, 6-dimethoxypyrinddin-2-yl) ureas 2 and N-(N-aryl-N-alkyl phosphoryl)-N'-(4, 6-dimethoxy pyrimidin-2-yl)ureas 3, were synthesized by treating N- (arylandnochlorophosphoryl ) - N'- (4, 6-dimethoxypyriAndinyl-2-) ureas 4 with alcohols or amines. Compounds 4 were obtained by reactingdichlorophosphoryl isocyanate with 4,6 - di meth oxy- 2-aminopyrimidine, and then with aromaticamines. The enzyme tests (in vitro) indicated that compounds 2 and 3 were two novel classes ofacetolactate synthase (ALS) inhibitors, which showed that the phosphoryl group, [-P(O)(OR)-], or[-P(O)(NHR)-], was a good bioisostere of the sulfonyl group (-SO2-) in sulfonylurea.