In order to better understand the structural and chemical features of c-Jun N-terminal kinase-1 (JNK-1), which is a member of the mitogen activated protein kinase (MAP kinase) family of enzymes responsible for the serine/threonine phosphorylation of intracellular targets, 3D-QSAR studies of some aminopyridine carboxamides as c-Jun N-terminal kinase inhibitors were performed by comparative molecular field analysis (CoMFA) to rationalize the structural requirements responsible for the inhibitory activity of these compounds. The genetic algorithm of GOLD3.1 has been employed to position 54 aminopyridine carboxamides in the active sites of JNK-1 to determine the probable binding conformation. The docking results provided a reliable conformational alignment scheme for 3D-QSAR model. Based on the docking conformations, highly predictive comparative molecular field analysis (CoMFA) was performed with a cross-validated q(2) of 0.585. The non-cross-validated analysis with six optimum components revealed a conventional r(2) value of 0.988, F=510.200, and an estimated standard error of 0.071. Furthermore, the CoMFA model was mapped back to the binding sites of JNK-1, to get a better understanding of vital interactions between the aminopyridine carboxamides and the kinase. Based on the docking and CoMFA analyses, we have identified some key features in the aminopyridine carboxamides that are responsible for JNK-1 inhibitory activity. The analyses may be used to design more potent aminopyridine carboxamides and predict their activity prior to synthesis.