853298-98-3

Upstream product

• 42533-63-1 1-(bromomethyl)-2-chloro-4-nitrobenzene 
• 121-86-8 2-chloro-4-nitrotoluene 

Downstream Products

• 853298-97-2 N-[4-(6-chloro-pyrimidin-4-yloxy)-phenyl]-N'-[4-(4-ethylpiperazin-1-ylmethyl)-3-chloro-phenyl]-urea 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of coumarin derivatives as novel acetylcholinesterase inhibitors that attenuate H2O2-induced apoptosis in SH-SY5Y cells

A novel series of coumarin derivatives were designed, synthesized and investigated for inhibition of cholinesterase, including acetyl cholinesterase (AChE) and butyrylcholinesterase (BuChE). This biological study showed that these compounds containing piperazine ring had significant inhibition activities on AChE rather than BuChE. Further study suggested that 9x, as one of this kind of structure derivative, showed the strongest inhibition activity on AChE with an IC50 value of 34?nM. Moreover, molecular docking, flow cytometry (FCM), and western blot assay suggested that 9x could induce cytoprotective autophagy to attenuate H2O2-induced cell death in human neuroblastoma SH-SY5Y cells. These findings highlight a new approach for the development of a novel potential neuroprotective compound targeting AChE with autophagy-inducing activity in future Alzheimer's disease (AD) therapy.

NOVEL INHIBITORS OF MAP4K1

The invention relates to novel inhibitors of MAP4K1 (HPK1) useful for the treatment of diseases or disorders characterised by dysregulation of the signal transduction pathways associated with MAPK activation, including hyperproliferative diseases, diseases of immune system dysfunction, inflammatory disorders, neurological diseases, and cardiovascular diseases. The invention further relates to pharmaceutical compositions comprising the same and methods of treatment of said diseases and disorders. The inhibitors are of formula (I) wherein the definitions for A, D, E, F, R5, R6, R7, Z, ring Q, n, x and y are as given in the application.

THERAPEUTIC INHIBITORS OF CDK8 AND USES THEREOF

The present invention relates to compounds formula (I) and to salts thereof, wherein R1-R4 have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of CDK8. Also included are pharmaceutically acceptable compositions comprising the compounds of the present invention and methods of using said compositions in the treatment of various disorders.

SUBSTITUTED PYRIMIDINYL AND PYRIDINYL-PYRROLOPYRIDINONES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS

The present invention relates to substituted pyrimidinyl- and pyridinylpyrrolopyridinone compounds which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular RET family kinases. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions containing these compounds.

DIARYL UREA DERIVATIVES IN THE TREATMENT OF PROTEIN KINASE DEPENDENT DISEASES

The invention relates to the use of diaryl urea derivatives for the manufacture of pharmaceutical compositions for the treatment of RET dependent disorders, especially RET dependent tumor diseases. The invention further relates to novel N-[4-(pyrimidin-4-yloxy)-phenyl]-N’-phenyl-urea derivatives and their use in the treatment of the animal or human body, especially in the treatment of a protein kinase dependent disease, to pharmaceutical compositions comprising such novel N-[4-pyrimidin-4-yloxy)-phenyl]-N’-phenyl-urea derivatives and to the use of such novel N-[4-(pyrimidin-4-yloxy)-phenyl]-N’-phenyl-urea derivatives for the preparation of pharmaceutical compositions for use in the treatment of protein kinase dependent diseases, especially of proliferative diseases, such as tumour diseases.