The Synthesis and Properties of Tricyclic Analogues of S⁶–MethylthioguanineandO⁶-Methylguanine

Abstract

The syntheses of novel tricyclic pyrrolo[2,3-d]pyrimidine analogues of O⁶–methylguanine and S⁶–methylthioguanine are described. The crystal structures and pK_a values of these analogues are reported. In a standard substrate assay with the human repair protein O⁶–methylguanine–DNA methyltransferase (MGMT) only the oxygen–containing analogue displayed activity.

Keywords:

• Pyrrolo[2,3–d]pyrimidines
• O ⁶ –methylguanine
• MGMT
• crystal structures, pK _a

Acknowledgments

We are grateful to Dr. Brian Taylor and Ms. Sue Bradshaw for NMR data, Mr. Simon Thorpe for mass spectra. We are also grateful to the EPSRC for financial support.