We define the connector region of a synthon as the fragment or set of fragments that we get by considering all atoms and bonds up to a specific distance from the connector, and by replacing all labeled connectors by unlabeled connectors. We denote the graph resulting from this procedure for a synthon s i by γ(s i ). We sort all synthons of each reaction according to their connector region with distance 3 bonds (see Fig. .2). We then apply this heuristic on the unlabeled query synthon substructures resulting from a cut set. A synthon reaction can be eliminated, if we do not find an injective mapping η from unlabeled fragments to synthon sets, such that for all unlabeled fragments f holds: in η(f ) exists a synthon with a connector region that contains the connector region of f as subgraph. We formulate the connector region heuristic as: