945396-55-4

Upstream product

• 945397-21-7 3,5-di(morpholino)aniline 
• 603-83-8 3-nitro-o-tolylamine 
• 26120-43-4 1-methyl-4-nitro-1H-indazole 
• 77894-69-0 1-methyl-1H-indazol-4-ylamine 
• 3819-88-3 1-fluoro-3-iodo-5-nitrobenzene 
• 1051899-19-4 4-(3-iodo-5-nitrophenyl)-morpholine 
• 220954-17-6 4,4’-(5-nitro-1,3-phenylene)dimorpholine 
• 2942-40-7 nitro-4 indazole 
• 1584164-82-8 4-(N-(2-chloropyrimidin-4-yl)amino-)-1-methyl-1H-indazole 

Relevant academic research and scientific papers

Development of indazolylpyrimidine derivatives as high-affine EphB4 receptor ligands and potential PET radiotracers

Due to their essential role in the pathogenesis of cancer, members of the Eph (erythropoietin-producing hepatoma cell line-A2) receptor tyrosine kinase family represent promising candidates for molecular imaging. Thus, the development and preparation of novel radiotracers for the noninvasive imaging of the EphB4 receptor via positron emission tomography (PET) is described. First in silico investigations with the indazolylpyrimidine lead compound which is known to be highly affine to EphB4 were executed to identify favorable labeling positions for an introduction of fluorine-18 to retain the affinity. Based on this, reference compounds as well as precursors were developed and labeled with carbon-11 and fluorine-18, respectively. For this purpose, a protecting group strategy essentially had to be generated to prevent unwanted methylation and to enable the introduction of fluorine-18. Further, a convenient radiolabeling strategy using [11C]methyl iodide was established which afforded the isotopically labeled radiotracer in 30-35% RCY (d.c.) which is identical with the original inhibitor molecule. A spiro ammonium precursor was prepared for radiolabeling with fluorine-18. Unfortunately, the labeling did not lead to the desired 18F-radiotracer under the chosen conditions.

PYRIMIDINE DERIVATIVES

The invention concerns benzamide compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, ring A, n, R3, and R4 are as defined in the description. The present invention also relates to processes for the preparation of such compounds, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of EphB4, and/or EphA2 and/or Src kinases.