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

Urea derivatives occupied a pivotal position in pesticide and medicinal chemistry due to their significant activities, including herbicidal activities, antimicrobial, anti-tumor, anti-HIV and so on. In this paper, the application and research progress of urea derivatives in the field of pesticide were reviewed. With the mankind’s environmental consciousness enhancing, it imparted the development of novel pesticides a new theme featured "super high effectivity, low toxicity, no residue." In order to develop novel urea derivatives, we have modified the main structure of them by structure link wory and bioisosterism principles. The active group N-nitro amine with plant growth regulating and herbicidal activities was introduced to substituted urea compounds to prepare a class of novel ureas with unique structure that linked the nitro group on the urea bridge. The novel ureas called N-nitro ureas. And the basic structure of them was shown:In this paper,38 N-nitro urea derivatives were synthesized. Base on their simultaneous bioassay results,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 N-nitro urea inhibitors.This paper mainly contains three parts as bellow.PartⅠ:38 N-nitro urea compounds were designed and synthesized form 2,4, 6-trichloroaniline as starting material by nitrification, formylation and ammonolysis. Ten of them are novel compounds. And the structures of these compounds were identified by IR,1H NMR.PartⅡ:the "Rape hypocotyl elongation test method", "Petri dish test for herbicidal bioactivity (NY/T 1155.1-2006)" and "Petri dish test for determining fungicide inhibition of mycelial growth (NY/T 1156.2-2006)" were respectively adopted to test the plant growth regulating, herbicidal and antifungal activities of target compounds. The preliminary bioassay results showed that:most of the target compounds possessed not so good plant growth regulating activities at 10 mg/L, but good herbicidal and antifungal activities under test concentration. Some of them showed more excellent herbicidal activities than herbicide Bensulfuron. The IC50 of antifungal activities of target compounds were about 50 mg/L and some of them possessed more significant antifungal activities than antifungal agent Carbendazim.PartⅢ:three-dimensional quantitative structure activity relationship (3D-QSAR)1. comparative molecular field analysis (CoMFA) was applied to study of 3D-QSAR on 38 N-nitro urea derivatives. The reasonable models with predictive ability were obtained from the investigation. A. retroflexus L:q2=0.674, r2=1.000, R2pred=0.9989 and S. sudanenses:q2=0.635,r2=1.000, R2pred=0.9958.2. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed based on our fungicidal activities data against Rhizoctonia solani. The best predictions were obtained with CoMFA standard model (q2=0.773, r2=0.959, R2pred=0.6624) and CoMSIA model combined with steric and electrostatic (q2=0.720, r2=0.936,R2pred=0.5682).3. 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.