Synthesis of intermediates of Potential Inhibitors of Enzyme P450 Aromatase in the Treatment of Breast Cancer

Abstract

We report the synthesis, analysis and optimization of the reaction conditions (e.g. best solvent, temperature and time) to enhance the yield of number of intermediates (i.e. para-substituted phenoxy propanols) of the final azole based inhibitors (i.e. para-substituted phenoxy alkyl azoles) which is considered to inhibit the production of estrogens by binding to the iron atom in the haem ring of aromatase P450 enzyme thus leading to the potential treatment of hormone dependant breast can­cer. Starting from phenol and range of substituted phenols various para-substituted phenoxy alkyl alcohols [i.e. compounds (22-26)] were synthesized. GC-MS, IR, NMR (13C & 1H) and TLC analysis of these compounds were also performed. Comparatively, a very good yield for compound 25 [3-(4-fluorophenoxy)propan-1-ol, 59.29 % yield] and compound 26 [3-(4-iodophenoxy)propan-1-ol, 55.49 %yield] were reported. In addition, to optimize the reaction condition for the synthe­sis of compounds (22-26), initially reaction was performed using dimethylformamide (DMF) as reaction solvent at various time intervals (i.e. 6, 12 and 24 hours) and various temperature (i.e. with heat and without heat). However, due to many laboratory based problems encountered with the use of this solvent especially the evaporation of this solvent; it was later on replaced with tetrahydrofuran (THF).Future work will involve multiple reaction steps for the synthesis of para-substituted phenoxy alkyl azoles from synthesized compounds (22-26) involving the removal of alcoholic group (OH) from the struc­ture and attachment of azole group (i.e. triazole or imidazole).

Journal of Chitwan Medical College 2013; 3(1): 37-41

DOI: http://dx.doi.org/10.3126/jcmc.v3i1.8464