1283087-68-2

Upstream product

• 1202273-87-7 3-(4-aminophenyl)-3-hydroxy-2,2-dimethylpropionic acid methyl ester 
• 1283087-62-6 3-hydroxy-2,2-dimethyl-3-(4-phenylaminophenyl)propionic acid methyl ester 
• 530-62-1 1,1'-carbonyldiimidazole 
• 555-16-8 4-nitrobenzaldehdye 
• 288-32-4 1H-imidazole 
• 98-80-6 phenylboronic acid 

Downstream Products

• 1391048-42-2 3-imidazol-1-yl-2,2-dimethyl-3-(4-phenylaminophenyl)propionic acid 

Relevant academic research and scientific papers

Novel retinoic acid 4-hydroxylase (CYP26) inhibitors based on a 3-(1H-imidazol- and triazol-1-yl)-2,2-dimethyl-3-(4-(phenylamino)phenyl)propyl scaffold

Retinoic acid (RA), the biologically active metabolite of vitamin A, is used medicinally for the treatment of hyperproliferative diseases including dermatological conditions and cancer. The antiproliferative effects of RA have been well documented as well as the limitations owing to toxicity and the development of resistance to RA therapy. RA metabolism inhibitors (RAMBAs or CYP26 inhibitors) are attracting increasing interest as an alternative method for enhancing endogenous levels of retinoic acid in the treatment of hyperproliferative disease. Here the synthesis and inhibitory activity of novel 3-(1H-imidazol- and triazol-1-yl)-2,2-dimethyl-3-(4-(phenylamino)phenyl)propyl derivatives in a MCF-7 CYP26A1 microsomal assay are described. The most promising inhibitor methyl 2,2-dimethyl-3-(4-(phenylamino)phenyl)-3-(1H-1,2,4- triazol-1-yl)propanoate (6) exhibited an IC50 of 13 nM (compared with standards Liarozole IC50 540 nM and R116010 IC50 10 nM) and was further evaluated for CYP selectivity using a panel of CYP with >100-fold selectivity for CYP26 compared with CYP1A2, 2C9 and 2D6 observed and 15-fold selectivity compared with CYP3A4. The results demonstrate the potential for further development of these potent inhibitors.

Small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26): Synthesis and biological evaluation of imidazole methyl 3-(4-(aryl-2-ylamino)phenyl) propanoates

The synthesis and potent inhibitory activity of novel imidazole methyl 3-(4-(aryl-2-ylamino)phenyl)propanoates in a MCF-7 CYP26A1 microsomal assay is described. The induction of CYP26A1 mRNA was used to evaluate the ability of the compounds to enhance the biological effects of all-trans retinoic acid (ATRA) in a retinoid-responsive neuroblastoma cell line. The most promising inhibitor, 3-imidazol-1-yl-2-methyl-3-[4-(naphthalen-2-ylamino)-phenyl]-propionic acid methyl ester (20), with an IC50 of 3 nM (compared with liarozole IC50 of 540 nM and R116010 IC50 of 10 nM) was further evaluated for CYP selectivity using a panel of CYP enzymes, mutagenicity (Ames screen), and hepatic stability.