111222-40-3

Upstream product

• 57508-48-2 carbethoxyacetamidine hydrochloride 
• 70-11-1 α-bromoacetophenone 
• 50551-10-5 ethyl amidinoacetate 
• 27317-59-5 Ethyl 3-ethoxy-3-iminopropionate 
• 105-56-6 ethyl 2-cyanoacetate 
• 2318-25-4 ethyl 3-ethoxy-3-iminopropanoate hydrochloride 

Downstream Products

• 173459-05-7 4-Chloro-6-phenyl-7H-pyrrolo[2,3-d]pyrimidine 
• 1222448-28-3 (R)-6-phenyl-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 
• 1350639-75-6 (R)-N-(1-(4-fluorophenyl)ethyl)-6-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 
• 173458-99-6 6-Phenyl-4-hydroxy-7H-pyrrolo[2,3-d]pyrimidine 
• 1643962-24-6 (S)-N-(2-methoxy-1-phenylethyl)-6-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 
• 1643962-22-4 (S)-2-phenyl-2-((6-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethanol 

Relevant academic research and scientific papers

4-AMINO-6-ARYL[2,3-D]PYRIMIDINES FOR THE INHIBITION OF EGFR TYROSINE KINASE

This invention relates to certain new pyrrolo-, thieno-, and furo-[2,3- d]pyrimidine compounds, such as of general formula (I) These compounds are epidermal growth factor receptor tyrosine kinase inhibitors and therefore offer potential in the treatment of cancer.

Activity of 6-aryl-pyrrolo[2,3-d]pyrimidine-4-amines to Tetrahymena

A series 6-aryl-pyrrolo[2,3-d]pyrimidine-4-amines (43 compounds), some of which are epidermal growth factor tyrosine kinase inhibitors, were tested for their protozoal toxicity using an environmental Tetrahymena strain as model organism. The protozoacidal activity of the analogues was found to be highly dependent on a 4-hydroxyl group at the 6-aryl ring, and a chiral 1-phenylethanamine substituent in position 4. Further, the potency was affected by the aromatic substitution pattern of the phenylethanamine: the unsubstituted, the meta-fluoro and the para-bromo substituted derivatives had the lowest minimum protozoacidal concentrations (8-16 μg/mL). Surprisingly, both enantiomers were found to have high potency suggesting that this compound class could have several modes of action. No correlation was found between the compounds protozoacidal activity and the in vitro epidermal growth factor receptor tyrosine kinase inhibitory potency. This suggests that the observed antimicrobial effects are related to other targets. Testing towards a panel of kinases indicated several alternative modes of action.

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.

3-Arylpiperazinylethyl-1H-pyrrolo[2,3-d]pyrimidine-2,4(3H,7H)-dione derivatives as novel, high-affinity and selective α1- adrenoceptor ligands

The discovery of a new series of selective and high-affinity α1-adrenoceptor (α1-AR) ligands, characterized by a 1H-pyrrolo[2,3-d]-pyrimidine-2,4(3H,7H)-dione system, is described in this paper. Some synthesized compounds, including 20, 22, and 30, displayed affinity in the nanomolar range for α1-ARs and substantial selectivity with respect to 5-HT1A and dopaminergic D1 and D 2 receptors. Functional assays, performed on selected derivatives, showed antagonistic properties.

Synthesis of 2-Amino-3-ethoxycarbonylpyrroles

Condensation of ethoxycarbonylacetamidine with α-bromoketones affords a versatile route to 2-amino-3-ethoxycarbonylpyrroles.Selective N-methylation is achieved under phase-transfer conditions.