The synthesis of novel acetolactate synthase inhibitors, N-(asymmetrically disubstituted phosphoryl)-N′-(4,6-dimethoxypyrimidin-2-yl) ureas
✍ Scribed by Guo-Feng Zhao; Hua-Zheng Yang; Yong-Hong Li
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 152 KB
- Volume
- 10
- Category
- Article
- ISSN
- 1042-7163
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✦ Synopsis
In view of the isosterism of the sulfonyl group(-SO 2 -) and the phosphoryl group, two new types of compounds N-(N-aryl-O-alkyl phosphoryl)-NЈ-(4,6dimethoxypyrimidin-2-yl) ureas (2) and N-(N-aryl-Nalkylphosphoryl) -NЈ -(4, 6 -dimethoxypyrimidin -2-yl) ureas (3) were designed and synthesized by treating N-(arylaminochlorophosphoryl) -NЈ -(4,6 -dimethoxypyrimidinyl-2-) ureas (4) with alcohols or amines. Compounds 4 were obtained by treating dichlorophosphoryl 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 that phosphoryl groups [-P(O)(OR)-, Rסalkyl] and [-P(O)(NHR), Rסalkyl] were likely to be good bioisosteres of the sulfonyl group (-SO 2 -) in the sulfonylureas.