Replacing central elements of known active structures is a common procedure to enter new compound classes. Different computational methods have already been developed to help with this task, varying in the description of possible replacements, the query input, and the similarity measure used. In this paper, a novel approach for scaffold replacement and a corresponding software tool, called Recore, is introduced. In contrast to prior methods, our main objective was to combine the following three properties in one tool: to avoid structures with strained conformations, to enable the exploration of large search spaces, and to allow interactive use through short response times. We introduce a new technique employing 3D fragments generated by combinatorial enumeration of cuts. It allows focusing on fragments suitable for scaffold replacement while retaining conformational information of the corresponding crystal structures. Based on this idea, we present an algorithm utilizing a geometric rank searching approach. Given a geometric arrangement of two or three exit vectors and additional pharmacophore features, the algorithm finds fragments fulfilling all these constraints ordered by increasing deviation from the query constraints. For the validation of the approach, three different design scenarios have been used. The results obtained show that our approach is able to propose new valid scaffold topologies.