173458-97-4

Upstream product

• 173458-92-9 2-amino-3-carboxethyl-5-(4-methoxyphenyl)-pyrrole 
• 77287-34-4 formamide 
• 2632-13-5 2-Bromo-4'-methoxyacetophenone 

Downstream Products

• 173459-03-5 4-chloro-6-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine 
• 1011717-24-0 (R)-N-(1-(4-fluorophenyl)ethyl)-6-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 
• 1220121-04-9 C₂₁H₁₉FN₄O 
• 1220121-05-0 C₂₁H₁₉FN₄O 
• 1220121-06-1 C₂₀H₁₇FN₄O 
• 1220121-07-2 C₂₀H₁₇FN₄O 
• 1220121-08-3 C₂₀H₁₇FN₄O 
• 1350639-66-5 (R)-N-(1-(4-bromophenyl)ethyl)-6-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 
• 1350639-67-6 (R)-6-(4-methoxyphenyl)-N-(1-p-tolylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 
• 1350639-68-7 6-(4-methoxyphenyl)-N-(1-(4-(trifluoromethyl)phenyl)ethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 
• 1350639-69-8 6-(4-methoxyphenyl)-N-(1-o-tolylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 
• 1350639-70-1 6-(4-methoxyphenyl)-N-(1-m-tolylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 
• 1011717-27-3 N-benzyl-6-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 
• 1350639-71-2 (R)-6-(4-methoxyphenyl)-N-(1-phenylpropyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 

Relevant academic research and scientific papers

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.

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

MULTI-FUNCTIONAL SMALL MOLECULES AS ANTI-PROLIFERATIVE AGENTS

The present invention relates to the compositions, methods, and applications of a novel approach to selective inhibition of several cellular or molecular targets with a single small molecule. More specifically, the present invention relates to multi-functional small molecules wherein one functionality is capable of inhibiting histone deacetylases (HDAC) and the other functionality is capable of inhibiting a different cellular or molecular pathway involved in aberrant cell proliferation, differentiation or survival.

FUSED BICYCLIC PYRIMIDINES AS PTK INHIBITORS CONTAINING A ZINC BINDING MOIETY

The present invention relates to fused bicyclic pyrimidine containing zinc- binding moiety based derivatives that have unique properties as protein tyrosine kinase (PTK) inhibitors and their use in the treatment of PTK related diseases and disorders such as cancer. The said derivatives may further act as HDAC inhibitors.

Pyrrolopyrimidines and processes for the preparation thereof

PCT No. PCT/EP96/02728 Sec. 371 Date Jan. 26, 1998 Sec. 102(e) Date Jan. 26, 1998 PCT Filed Jun. 24, 1996 PCT Pub. No. WO97/02266 PCT Pub. Date Jan. 23, 1997Described are 7H-pyrrolo[2,3-d]pyrimidine derivatives of formula I wherein the symbols are as defined in claim 1. Those compounds inhibit tyrosine protein kinase and can be used in the treatment of hyperproliferative diseases, for example tumour diseases.