497841-36-8

Upstream product

• 20099-89-2 4-Cyanophenacyl bromide 
• 497841-35-7 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)benzonitrile 
• 3886-69-9 (R)-1-phenyl-ethyl-amine 
• 497841-34-6 4-(4-hydroxy-7H-pyrrolo[2,3-d]pyrimidin-6-yl)benzonitrile 
• 497841-33-5 ethyl 2-amino-5-(4-cyanophenyl)-1H-pyrrole-3-carboxylate 
• 618-36-0 rac-methylbenzylamine 

Downstream Products

• 497841-37-9 [6-(4-aminomethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenyl-ethyl)-amine 

Relevant academic research and scientific papers

Synthesis and in vitro EGFR (ErbB1) tyrosine kinase inhibitory activity of 4-N-substituted 6-aryl-7H-pyrrolo[2,3-d]pyrimidine-4-amines

A series of 4-N-substituted 6-aryl-7H-pyrrolo[2,3-d]pyrimidine-4-amines have been synthesised, characterised and tested for their in vitro EGFR (ErbB1) tyrosine kinase inhibitory activity. The compounds were prepared from ethyl cyanoacetate and α-bromoacetophenones via the 2-amino-3-ethoxycarbonyl-5- aryl-pyrroles and 4-chloro-6-arylpyrrolopyrimidines. Aromatic substitution with benzylic amines was performed by conventional thermal substitution, and palladium catalysed coupling. The two methods resulted in similar yields, but the palladium coupling had the benefit of lower chemical consumption and reduced reaction times. Eight of the new compounds had IC50 values in the range of 2.8-9.0 nM. Four of these have a fluorine atom positioned at sites otherwise potentially susceptible to oxidative metabolism. Structural variation of the 6-aryl group indicated that the inhibitory action was only moderately sensitive to modifications in this fragment. However, the potency depended strongly on the structure of the aromatic part of the 4-amino group, and any aromatic substitution except fluorine reduced the in vitro activity. The cellular EGFR internalization response of selected compounds was evaluated using HeLa cells. Three fluorinated derivatives had a pronounced effect in inhibiting EGFR internalization.

7H-pyrrolo[2,3-d]pyrimidine derivatives

The invention relates to 7H-pyrrolo[2,3-d]pyrimidine derivatives of formula I wherein the symbols and substituents are as defined in the description, to processes for the preparation thereof, to pharmaceutical compositions comprising such derivatives and to the use of such derivatives—alone or in combination with one or more other pharmaceutically active compounds—for the preparation of pharmaceutical compositions for the treatment especially of a proliferative disease, such as a tumour.