1220121-04-9

Basic information

• Product Name: C₂₁H₁₉FN₄O
• Synonyms: C₂₁H₁₉FN₄O
• CAS NO: 1220121-04-9
• Molecular Weight: 362.406
• Mol File: 1220121-04-9.mol

Chemical Properties

• CAS DataBase Reference: C₂₁H₁₉FN₄O(CAS DataBase Reference)
• NIST Chemistry Reference: C₂₁H₁₉FN₄O(1220121-04-9)
• EPA Substance Registry System: C₂₁H₁₉FN₄O(1220121-04-9)

Safety Data

• Hazardous Substances Data: 1220121-04-9(Hazardous Substances Data)

Upstream product

• 2632-13-5 2-Bromo-4'-methoxyacetophenone 
• 173458-97-4 4-hydroxy-6-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine 
• 761390-58-3 (R)-(-)-1-(3-fluorophenyl)ethylamine 
• 173459-03-5 4-chloro-6-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine 
• 173458-92-9 2-amino-3-carboxethyl-5-(4-methoxyphenyl)-pyrrole 
• 444643-09-8 (S)-3-fluoro-α-methylbenzylamine 

Downstream Products

• 1350639-86-9 (R)-4-(4-((1-(3-fluorophenyl)ethyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenol hydrobromide 
• 1350698-90-6 C₂₀H₁₇FN₄O 

Relevant articles and documents

Identification of new 4-N-substituted 6-aryl-7H-pyrrolo[2,3-d]pyrimidine-4- amines as highly potent EGFR-TK inhibitors with Src-family activity

The epidermal growth factor receptor is an important target in molecular cancer therapy. Herein, the enzymatic inhibition potential of a series of chiral and non chiral pyrrolopyrimidine based derivatives have been investigated and optimised. Overall, seven new compounds were identified having enzymatic IC 50 values comparable to or better than the commercial drug Erlotinib. High activity was also confirmed towards the epidermal growth factor receptor L858R and L861Q mutants. Based on calculated druglike properties, eight compounds were further evaluated towards a panel of 52 other kinases revealing interesting Src-family kinase and colony stimulating factor 1 receptor kinase inhibitory activity. Cell proliferation studies with the cell lines A431, C-33A, AU-565, K-562 and genetically engineered Ba/F3-EGFRL858R cells also showed several molecules to be more active than Erlotinib, and thus confirming these pyrrolopyrimidines as attractive drug candidates or lead structures.

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.

1H,13C and19FNMR data of N-substituted 6-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amines in DMSO-d6

Chemical shift assignment of seven N-substituted 6-(4-methoxyphenyl)-7H- pyrrolo[2, 3-d]pyrimidin-4-amines, six of which are fluorinated, have been performed based on 1H, 13C, 19F, and 2D COSY, HMBC and HSQC experiments. C