ABSTRACT
A series of novel 4-(4-(5-methyl-3-arylisoxazol-4-yl)thiazol-2-yl)piperidyl carboxamides and thiocarboxamides were synthesized as potential lead compounds of inhibitors targeting D1 protease in plants. These compounds were designed on the basis of a D1 protease inhibitor hit structure identified by homology modeling and virtual screening. The syntheses of these compounds were accomplished via a four-step procedure including the isoxazole ring formation, alpha-bromination of acetyl group, thiazole ring formation, and carboxamide/thiocarboxamide attachment. The in vivo herbicidal activity tests show that most compounds possess moderate to good herbicidal activities. The enzyme activity of one compound against the native spinach D1 protease exhibits a competitive inhibition. The results suggest that these compounds are indeed potential inhibitors for targeting D1 protease in plants.
Subject(s)
Herbicides/chemical synthesis , Piperidines/chemical synthesis , Plant Proteins/antagonists & inhibitors , Protease Inhibitors/chemical synthesis , Binding, Competitive , Computer Simulation , Herbicides/pharmacology , Isoxazoles , Models, Molecular , Piperidines/pharmacology , Protease Inhibitors/pharmacology , Spinacia oleracea/enzymology , ThiazolesABSTRACT
In the title molecule, C(26)H(24)N(4)O(2)S, the dihedral angle between the isoxazole ring and the adjoining benzene ring is 21.4â (5)°, and between the isoxazole ring and the thia-zole ring is 14.3â (4)°. The piperidine ring is in a chair conformation. In the crystal structure, mol-ecules are linked by inter-molecular N-Hâ¯O and weak C-Hâ¯O hydrogen bonds into one-dimensional chains along [001].
