Study on the design, synthesis and bioactivity of novel ALS inhibitors (VII) - The synthesis of novel acetolactate synthase inhibitors, N-(asymmetrically disubstituted phosphoryl)-N '-(4,6-dimethoxypyrimidin-2-yl) ureas

In view of the isosterism of the sulfonyl group(-SO2-) and the phosphoryl g roup, two new types of compounds N-(N-aryl-O-alkyl phosphoryl)-N'-(4,6-dime thoxypyrimidin-2-yl) ureas (2) and N-(N-aryl-N-alkylphosphoryl)-N'-(4,6-dim ethoxypyrimidin-2-yl) ureas (3) were designed and synthesized by treating N -(arylaminochlorophosphoryl)-N'-(4,6-dimethoxypyrrimidinyl-2-)ureas (4) wit h alcohols or amines. Compounds 4 were obtained by treating dichlorophospho ryl isocyanate with 4,6-dimethoxy-2-aminopyrimidine and then with aromatic amines. The enzyme tests in vitro indicated that compounds 2 and 3 were two novel classes of acetolactate synthase (ALS) inhibitors and also showed th at phosphoryl groups [-P(O)(OR)-, R=alkyl] and [-P(O)(NHR), R=alkyl] were l ikely to be good bioisosteres of the sulfonyl group (-SO2-) in the sulfonyl ureas. (C) 1999 John Wiley & Sons, Inc.