Theophylline derivatives have long been recognized as potent bronchodilators for the relief of acute asthma. Recently, it was found that bacterial infection has a role in asthma pathogenesis. The present work involves the design and synthesis of 8-substituted theophylline derivatives as bronchodilators and antibacterial agents. The chemical structures of these compounds were elucidated by IR, (1)H-NMR, mass spectrometry, and elemental analyses. The bronchodilator activity was evaluated using acetylcholine-induced bronchospasm in guinea pigs, and most of the compounds showed significant anti-bronchoconstrictive activity in comparison with standard aminophylline. In addition, the antibacterial activity of all the target compounds was investigated in vitro against Gram-positive and Gram-negative bacteria using ampicillin as a reference drug. Results showed that some of the tested compounds possessed significant antibacterial activity. A pharmacophore model was computed to obtain useful insight into the essential structural features of bronchodilator activity. A structure activity relationship was also discussed.