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

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.This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0070920 and 2010-0012838). J. Lee and S. Yoon acknowledge financial support from the Korean Ministry of Education through the second stage of the BK21 and the BK21-Plus project for the Hanyang University graduate program. We thank Prof. H. Chun for X-ray crystallography