Preliminary SAR analysis of novel antiproliferative N(6),5'-bis-ureidoadenosine derivatives

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 23; pp. 6775 - 6779
• Main Authors: Peterson, Matt A, Oliveira, Marcelio, Christiansen, Michael A, Cutler, Christopher E
• Format: Journal Article
• Language: English
• Published: England 01-12-2009
• Subjects: Adenosine - analogs & derivatives; Adenosine - chemical synthesis; Adenosine - chemistry; Adenosine - pharmacology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Drug Screening Assays, Antitumor; Humans; Methylurea Compounds - chemical synthesis; Methylurea Compounds - chemistry; Methylurea Compounds - pharmacology; Molecular Structure; Stereoisomerism; Structure-Activity Relationship
• ISSN: 1464-3405
• DOI: 10.1016/j.bmcl.2009.09.083

A preliminary library of novel N(6),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 N(6)- nor 5'-ureido substituents were sufficient to achieve significant antiproliferative effects when present in the absence of the other. The 2'-O-TBS, and N(6),5'-bis-ureido substitution patterns were found to be necessary for optimal antiproliferative activity.