AbstractBACKGROUNDAgrochemicals have been crucial to the production of food, and the need for the development of novel agrochemicals continues unceasing owing to the loss of existing produces via the growth of resistance and the desire for products with more propitious environmental and toxicological patterns.RESULTSThe results of both CoMFA and CoMSIA models indicated that biological activity can effectively be improved through the structural optimisation and molecular design of these synthetic compounds from the aspects of steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor fields. Data of postemergence herbicidal activity in the greenhouse explained that most new 3‐(pyridin‐2‐yl)benzenesulfonamide derivatives (4c–4 t) could control highly effectively against barnyardgrass, foxtail, vetleaf, and youth and old age (herbicidal activity ≥90%); for example, compounds 4q–4 t exhibit excellent biological activity equivalent/superior to commercial saflufenacil/sulcotrione at the low concentration of 37.5 g a.i./ha, and in particular, the herbicidal activity of compound 4 t for four experimental plant species is found to be notably greater than saflufenacil (3.75 g a.i./ha). Meanwhile, compound 4 t also has good crop selectivity for weed control in maize.CONCLUSIONThe novel compounds such as 4 t have remarkable biological activity after the structural optimisation utilising the constructed 3D‐QSAR models, i.e. such QSAR models have great accuracy. © 2017 Society of Chemical Industry