Synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors.

Synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors.
Bioorg Med Chem Lett. 2020 Sep 05;:127525
Authors: Zhang Q, Zhao K, Zhang L, Jiao X, Zhang Y, Tang C
Abstract
As a class III receptor tyrosine kinase (RTK), FMS-like tyrosine kinase 3 (FLT3) is always overexpressed in many cases of acute leukemia. This paper studies the structure-based synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors. Encouragingly, compounds 15b, 16b, 24a, and 24c showed excellent biological activities in a low nanomolar range. In particular, compound 16b demonstrated significant inhibitory potency against FLT3-ITD (IC50 = 5.60 nM) and better antiproliferative activity than quizartinib against MV4-11 cell line (IC50 = 0.176 nM). It is indicated that compound 16b for the treatment of acute myeloid leukemia could be very promising.
PMID: 32898697 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry Letters - September 4, 2020 Category: Chemistry Authors: Zhang Q, Zhao K, Zhang L, Jiao X, Zhang Y, Tang C Tags: Bioorg Med Chem Lett Source Type: research