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.
A narrow selectivity profile, limited metabolism and a reliable SAR suggest the little explored biphenyl pyrazoyl-urea scaffold as a promising chemotype for the development of FLT3-targeting drugs for the treatment of AML.
Novel FLT3/CHK1 dual agents, the representative compound 30, with favorable oral PK properties, can overcome multiple FLT3-TKD and FLT3-ITD mutations.
The development of macrocycles has emerged as an innovative approach to improve kinase inhibitor selectivity, as well as pharmacokinetic and pharmacodynamic properties.
Fluorinated pyrimidine-5-carboxamide MERTK inhibitors with nanomolar potency and >5-fold selectivity over AXL, TYRO3, and FLT3, with leading compounds being 1a, 2c and 3b. Potential 18F-PET radioligands to image protective microglia in MS.