Dual FLT3/haspin kinase inhibitor based on 3H-pyrazolo[4,3-f]quinoline scaffold with activities against acute myeloid leukemia.

ABSTRACT: The 3H-pyrazolo[4,3-f]quinoline core, a privileged fusion moiety from quinoline and indazole, facilely synthesized in a one flask multi-component Doebner-Povarov reaction, is a newly described kinase hinge binder. Previous works have demonstrated that the 3H-pyrazolo[4,3-f]quinoline moiety can be tuned, via judicious substitution patterns, to selectively inhibit cancer-associated kinases, such as FLT3 and haspin. A first generation 3H-pyrazolo[4,3-f]quinoline-based haspin inhibitor, HSD972, and FLT3 inhibitor, HSD1169, were previously disclosed as inhibitors of various cancer cell lines. Given the recent revelation that haspin is over-expressed and plays critical proliferative roles in many cancers, and compounds with dual activity against F

SUBMITTER: Kempen AL 

PROVIDER: S-EPMC10507812 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature