Boronic acids and boronate esters are commonly used reagents in Suzuki–Miyaura coupling chemistry. Organoboron derivatives are common reagents for C–C bond formation, either through classical palladium-mediated transformations or through other newer coupling methods. Boronic esters and acids are potential intermediates in the manufacture of many active pharmaceutical ingredients (API).
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Cyclopropane is the smallest cyclic compound with unique structural features and physicochemical properties, which is widely used in the design of small molecule drugs. In drug design, it is often used to increase activity, fix conformation and improve PK and water solubility. The introduction of cyclopropyl groups into drugs can change various properties of molecules, such as improving metabolic stability; increasing biological activity; enhancing drug efficacy; limiting polypeptide conformation and slowing down its hydrolysis; reducing plasma clearance; improving drug dissociation and many more. Cyclopropane rings are widely found in marketed drugs, including cardiovascular drugs, central nervous system (CNS) drugs, anticancer drugs, autoimmune and anti-inflammatory drugs.
Venetoclax (VEN) combined with a hypomethylating agent (HMA) has proven effective for treating acute myeloid leukemia (AML) patients who are ineligible for intensive chemotherapy. However, this combination therapy still faces issues such as low response rates, limited survival, and potential resistance to VEN.
Aptose’s Tuspetinib (TUS) is a multi-kinase inhibitor selectively targeting SYK, RSK, FLT3 , JAK1/2, KIT, which drive proliferation in AML. The addition of Tuspetinib into VEN and HMA therapy improves medical efficacy and and may help prevent resistance to both agents. TUS+VEN+HMA triplet protocol in frontline therapy for newly diagnosed (ND) AML is currently being tested in a global phase 1/2 trial.
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