THE SYNTHESIS AND EVALUATION OF NEW CARBOCYCLIC PYRROLO[2,3-d]PYRIMIDINE NUCLEOSIDE ANALOGS

Abstract

New carbocyclic pyrrolo[2,3-d]pyrimidine nucleoside analogs were synthesized with the key intermediate, 4-amino-6-bromo-5-cyanopyrrolo[2,3-c]pyrimidine (2), by S(N)2 reaction. One of the products, 4-amino-6-bromo-1-cyclopentyl-1H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (9), showed significant anti-proliferative activity to the human ovarian cancer PA-1 cells (IC50: 3.9 mu M). 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]-17H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (15) showed very similar antiproliferative activity (IC50: 2.6 mu M) when compared to compound 9.