THE SYNTHESIS AND EVALUATION OF NEW CARBOCYCLIC PYRROLO2,3-dPYRIMIDINE NUCLEOSIDE ANALOGS

摘要

New carbocyclic pyrrolo2,3-dpyrimidine nucleoside analogs were synthesized with the key intermediate, 4-amino-6-bromo-5-cyanopyrrolo2,3-dpyrimidine (2), by S_n2 reaction. One of the products, 4-amino-6-bromo-l-cyclopentyl-1H-pyrrolo2,3-dpyrimidine-5-carboxamide (9), showed significant anti-proliferative activity to the human ovarian cancer PA-1 cells (IC50: 3.9 uM). Based on the biological effects and the functional group characteristics of the compound 9, other carbocyclic nucleoside analogs related to the compound 9 were synthesized with key intermediate 2 by a Pd(0)-catalyzed coupling reaction. As expected, syn-4-amino-6-bromo-7-4-(methoxymethyl)-2-cyclopenten-1-yl-7H-pyrrolo2,3-dpyrimidine-5-carboxamide (15) showed very similar antiproliferative activity (IC50: 2.6 uM) when compared to compound 9.