45859-82-3Relevant academic research and scientific papers
BENZENE FUSED HETEROCYCLIC COMPOUND AND USE THEREOF
-
Paragraph 0280; 0281; 0285; 0286, (2019/06/17)
The present disclosure provides a benzene fused heterocyclic compound of Formula (I): wherein (A) is a single or double bond; n is 0 or 1; X is -CH2-, O, NR1, or S; A is -C(Ra1)(Ra2)(Ra3) or -N(R
Discovery of dual death-associated protein related apoptosis inducing protein kinase 1 and 2 inhibitors by a scaffold hopping approach
Gao, Ling-Jie,Kovackova, Sona,?ála, Michal,Ramadori, Anna Teresa,De Jonghe, Steven,Herdewijn, Piet
, p. 7624 - 7643 (2015/01/08)
DRAK2 emerged as a promising drug target for the treatment of autoimmune diseases and to prevent graft rejection after organ transplantation. Screening of a compound library in a DRAK2 binding assay led to the identification of an isothiazolo[5,4-b]pyridine derivative as a novel ligand for DRAK2, displaying a Kdvalue of 1.6 μM. Subsequent medicinal chemistry work led to the discovery of a thieno[2,3-b]pyridine derivative with strong DRAK2 binding affinity (Kd= 9 nM). Moreover, this compound also behaves as a functional inhibitor of DRAK2 enzymatic activity, displaying an IC50value of 0.82 μM, although lacking selectivity, when tested against DRAK1. This paper describes for the first time functionally active dual DRAK1 and DRAK2 inhibitors that can be used as starting point for the synthesis of chemical tool compounds to study DRAK1 and DRAK2 biology, or they can be considered as hit compounds for hit-to-lead optimization campaigns in drug discovery programs.
