Study On Synthesis, Biological Activities And 3D-QSAR Of Fluorine-Containing N-Nitro Urea Derivatives

Urea derivatives played a pivotal position in pesticides, medicines and chemical due to their variety activities, including herbicidal activities, antibacterial, plant growth regulating and so on. By consulting concerned literatures, in this paper we reviewed the synthetical methods and the biological activities of urea derivatives. Organofluorine began to be taken seriously since the 70s. Most of fluorine-containing pesticides with "super high effectivity, low toxicity, no residue" features, has become one of the central issue of new pesticides. In order to seek high-activity substances, we have modified the main structure of N-nitro ureas by Bioisosterism Principles and Substructure Link Wory. The fluorine atom was introduced to N-nitro urea compounds to synthesize 22 unreported fluorine-containing N-nitro substituted ureas. And the basic structure of them was shown as follow:Expored their activities of target compounds. Then 3D-QSAR of N-nitro urea derivatives was analyzed. The credible 3D-QSAR models were established which are useful in understanding the detail of the relationship of the structure and bioactivity. Thus it could more effectively direct the design of new potential fluorine-containing N-nitrourea inhibitors.This paper mainly contains three parts as bellow.1. Synthesis and Characterization:Intermediates 2,6-dibromo-4-fluoro-N-nitroaniline were synthesized from 4-fluoroaniline as starting material by acetylation, sulfonation, bromination and N-nitration. Twenty-two target compounds were designed and synthesized via a simple and convenient BTC'one-pot'procedure used DMAP as catalyst. The structures of them were confirmed by IR,1H NMR, and a part have been identified by 13C NMR. 2. Activity tests:the "Petri dish test for herbicidal bioactivity (NY/T 1155.1-2006)", "Rape hypocotyl elongation test method" and "Petri dish test for determining fungicide inhibition of mycelial growth (NY/T 1156.2-2006)" were respectively adopted to test the herbicidal, plant growth regulating and antifungal activities of target compounds. The preliminary bioassay indicated that:most of the target compounds possessed good herbicidal activities against Amaranthus albus and Sorghum sudanense, the IC50 of which were about 100 mg/L. Compound 4a and 4f showed good plant growth regulating activities at 10 mg/L. Good antifungal activities under test concentration, and antifungal activities against Sclerotinia sclerotiorum is better than Rhizoctonia solani.3. Three-dimensional quantitative structure activity relationship (3D-QSAR): comparative molecular field analysis (CoMFA) was applied to study of 3D-QSAR on 22 fluorine-containing N-nitrourea derivatives. The reasonable models with predictive ability were obtained from the investigation. The 3D-QSAR model were validated and evaluated. The steric and electrostatic maps were obtained which were applied in elucidating the relationship between the ligand and the bingding site of receptor.