Huayin Liu

QSAR and 3D-QSAR analysis of structurally diverse ALS inhibitors: sulfonylureas and triazolopyrimidine-2-sulfonamides

For the purpose of better understanding the molecular mechanism of action of sulfonylurea and sulfonamide herbicides, the quantitative relationship between their structure and herbicidal activity against rape, Brassica campestris L, was analysed using physicochemical parameters and regression analysis and comparative molecular field analysis (CoMFA). The results showed that the structure–activity relationships of the two sets of compounds were identical, which suggested that the two different sets of compounds affect a common region of the receptor site. The CoMFA results were consistent with those derived from traditional QSAR analysis. Combining the traditional QSAR analysis with the CoMFA results, we can conclude that the variations in the herbicidal activity of the two sets of ALS inhibitors were governed dominantly by the three-dimensional steric and electrostatic field parameters of molecules participating in the interaction with the receptor site and there is apparently an optimum electronic property (Σσ or pKa) for the molecules to fit the receptor. © 1999 Society of Chemical Industry

SYNTHESIS OF NOVEL DERIVATIVES OF 2-CYANO-3-METHYLTHIO-3'-BENZYLAMINO ACRYLATES(ACRYLAMIDES) AND THEIR BIOLOGICAL ACTIVITY

Abstract A series of new substituted derivatives of 2-cyano-3-methvlthio-3′-aminoacrylates(acrylamides) have been designed and synthesized. Their structures were confirmed by 1h NMR and elemental analysis. The bioassay test indicates that most of these new compounds show good Hill reaction inhibitory activity.

Design, synthesis and bioactivity of novel ALS inhibitors (V)

By means of the X-ray diffraction method, quantum pharmacology analysis and quantitative structure-activity relationships (QSAR) analysis, the structure-activity relationships of the herbicidal sulfonylureas and fused heterocyclic sulfonamides were systematically studied. The results showed that the structure-activity relationships of these two kinds of herbicides were identical and that the heterocyclic ring and sulfonyl moiety in the molecules were their pharmacophores which likely bind in the same receptor sites of acetolactate synthase (ALS). According to these results, the initial model of these two kinds of herbicides binding with the receptor was put forward.

A Facile Synthesis of 3-Aryl-5-cyano-6-methylthio-pyrimidine-2,4-diones

Abstract Novel derivatives of 3-aryl-5-cyano-6-methylthiopyrimidine-2,4-diones were synthesized, under mild conditions, by the reaction of ethyl 2-cyano-3,3′dimethylthioacrylate with arylureas.

Structure based library approach to photosynthesis inhibitors:Combinatorial synthesis of hydrouracil library

Based on the binding mode for hydrouracil in photosystem II (PS II) Dl protein, a general method for the solid phase combinatorial synthesis of hydrouracil library was developed. The acryloyl chloride or acid were coupled to Wang resin1 to afford the acryloyl ester2. Resin bound ester2 reacted with various primary amines to give secondary amines3, which were converted to the resin bound ureas4 by treatment with isocyanates. Preparation of the hydrouracils5 was achieved by the acidic cyclization-cleavage from the resin. For characterization purposes,8 hydrouracil analogues were synthesized in parallel, following which a small library of9 hydrouracil derivatives was prepared after cleavage from Wang resin. All the9 bydrouracil derivatives desired were identified by GCMS.