Preliminary SAR analysis of novel antiproliferative N6,5′-bis-ureidoadenosine derivatives

A preliminary library of novel N6,5′-bis-ureidoadenosine analogs and related derivatives was prepared and tested for activity against the NCI 60 panel of human cancers. A 2′-O-TBS group was found to be necessary, but not sufficient, for optimal antiproliferative activity. Neither the N6- nor 5′-ureido substituents were sufficient to achieve significant antiproliferative effects when present in the absence of the other. The 2′-O-TBS, and N6,5′-bis-ureido substitution patterns were found to be necessary for optimal antiproliferative activity.

Analogs of lead antiproliferative agent 1 were prepared and tested for activities against the NCI 60 panel of human cancers. Variants in all four canonical quadrants were tested. The 2′-O-TBS, 5′-N-methylurea, and N6-phenylurea were necessary for optimal activity.Figure optionsDownload as PowerPoint slide