The concept of crystal engineering and supramolecular synthesis has enabled the generation of a diverse range of multicomponent crystalline pharmaceutical solids (i.e. co-crystals), which can improve the performance and functionality of known drugs [1]. The rational design of co-crystals is based on reliable supramolecular synthons and different co-crystal formers for fine-tuning the properties of new compositional matter, which are expected to be different from the pure form of the drug. This methodology is not routine still and understanding of factors which lead to successful or unsuccessful co-crystallization represents the challenge to modern crystal engineering. Two antitubercular drugs, 2-Ethyl- and 2-Propyl-4-thiocarbamoylpyridine were employed in two parallel series of co-crystallizations with homologous alkanedicarboxylic acids (COOH-(CH2)n-COOH, n=0-7) and 18-membered crown ethers. Co-crystals having 2:1 drug:co-crystal former stoichiometry have been obtained with adipic and suberic acids (n-4, 6) and 18-crown-6 and B isomer of DCH18-crown-6. No co-crystals were isolated with other dicarboxylic acids. In the co-crystals, the dicarboxylic acid invariably interacts with both nitrogen atoms of drug molecules via O-H…N and N-H…O hydrogen bonds, resulting in the similar H-bonds pattern regardless of S-shape or linear conformation of dicarboxylic acid. Only the amino group of the drug participates in H-bonding with the crown ether, whereas the best acceptor of the drug (i.e. aromatic N) doesn’t form any strong Hbond. The crown ether breaks the reliable homosynthon of thioamide group, which was found in co-crystals with dicarboxylic acids.