Serum and glucocorticoid-regulated kinases (SGKs) are members of the AGC kinase family and consist of three isoforms: SGK1, SGK2, and SGK3. SGK1 is a potential target for cancer therapy because the overexpression of SGK1 has caused irregular cell proliferation, leading to solid human tumors. This study has investigated the structure-activity relationship (SAR) of a series of novel pyrrolo[2,3-b]pyridine derivatives with potential anticancer activity. Eighteen compounds were synthesized and evaluated for their inhibitory activities against SGK1, 2 and 3. SAR analysis was performed in order to identify the key structural features influencing the bioactivity of the compounds.