Novel acylureidoindolin-2-one derivatives as dual Aurora B/FLT3 inhibitors for the treatment of acute myeloid leukemia was written by Jagtap, Ajit Dhananjay;Chang, Pei-Teh;Liu, Jia-Rong;Wang, Hsiao-Chun;Kondekar, Nagendra B.;Shen, Li-Jiuan;Tseng, Hsiang-Wen;Chen, Grace Shiahuy;Chern, Ji-Wang. And the article was included in European Journal of Medicinal Chemistry in 2014.Safety of 3,4-Dichlorobenzamide This article mentions the following:
A series of 6-acylureido derivatives containing a 3-(pyrrol-2-ylmethylidene)indolin-2-one scaffold were synthesized as potential dual Aurora B/FLT3 inhibitors by replacing the 6-arylureido moiety in 6-arylureidoindolin-2-one-based multi-kinase inhibitors. (Z)-N-(2-(pyrrolidin-1-yl)ethyl)-5-((6-(3-(2-fluoro-4-methoxybenzoyl)ureido)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide I was identified as a dual Aurora B/FLT3 inhibitor (IC50 = 0.4 nM and 0.5 nM, resp.). Compound I also exhibited potent cytotoxicity with single-digit nanomolar IC50 values against the FLT3 mutant-associated human acute myeloid leukemia (AML) cell lines MV4-11 (FLT3-ITD) and MOLM-13 (FLT3-ITD). Compound I also specifically induced extrinsic apoptosis by inhibiting the phosphorylation of the Aurora B and FLT3 pathways in MOLM-13 cells. Compound I had a moderate pharmacokinetic profile. The mesylate salt of I efficiently inhibited tumor growth and reduced the mortality of BALB/c nude mice (s.c. xenograft model) that had been implanted with AML MOLM-13 cells. Compound 54 is more potent than sunitinib not only against FLT3-WT AML cells but also active against sunitinib-resistant FLT3-ITD AML cells. This study demonstrates the significance of dual Aurora B/FLT3 inhibitors for the development of potential agents to treat AML. In the experiment, the researchers used many compounds, for example, 3,4-Dichlorobenzamide (cas: 2670-38-4Safety of 3,4-Dichlorobenzamide).
3,4-Dichlorobenzamide (cas: 2670-38-4) belongs to amides. Because of the greater electronegativity of oxygen, the carbonyl (C=O) is a stronger dipole than the N–C dipole. The presence of a C=O dipole and, to a lesser extent a N–C dipole, allows amides to act as H-bond acceptors. Amides can be freed from solvent or water by drying below their melting points. These purifications can also be used for sulfonamides and acid hydrazides.Safety of 3,4-Dichlorobenzamide
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics