Cancer is one of the most prevalent causes of death worldwide, with an estimated 609,820 deaths expected in the United States in 2023 . Anticancer drugs are critical in fighting cancer by modulating specific molecular targets essential for cancer cell growth and survival . Carbonic anhydrases (CAs) are a family of enzymes that play a vital role in various biological processes, including tumor progression . Two members of this family, CA IX and CA XII, play a role in oncogenesis, with CA IX being overexpressed in various types of cancer, including cervical cancer . Carbonic anhydrase inhibitors (CAIs) are a well-known class of drugs with clinical applications in treating glaucoma, epilepsy, and edema . Substituted coumarins constitute a category of non-classical CAIs designed specifically to target oncogenic CAs, with patented structures owned by Metasignal Therapeutics Inc. . 3-substituted coumarins have a diverse pharmacological space, including anticancer activity by modulating the activity of tumor-associated carbonic anhydrases . This study aims to probe the synthetically feasible chemical space of 3-substituted coumarins with potential activity against carbonic anhydrases IX and XII. We implemented a ChEMBL activity-informed approach, somewhat resembling the Polypharmacology Browser PPB2 , to explore the pharmacological potentials of a novel series of 52 randomly sketched synthetically feasible 3-substituted coumarins. Using DataWarrior, we mined the ChEMBL database for actives similar to those sketched coumarins based on the FragFp Descriptor.