Pyrrolo[3,2-D]Pyrimidines, a New Class of Purine Nucleoside Phosphorylase (PNP) Inhibitors as Potential T-Cell Selective Immunosuppressive Agents
- 1 January 1991
- book chapter
- Published by Springer Nature
Abstract
Previously, we have described the synthesis and biological activity of 2,8-diamino-1,9-dihydro-9-(2-thienylmethyl)-6H-purin-6-one (PD 119229; CI-950) as a potent and competitive PNP inhibitor. As a part of our continuing efforts to develop a PNP inhibitor for autoimmune diseases, we have synthesized a series of pyrrolo[3,2-d]-pyrimidines as PNP inhibitors. In this series, 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo- [3,2-d]pyrimidin-4-one (CI-972) was found to be a potent, competitive inhibitor of PNP with Ki of 0.83 μM. It was also found to be selectively cytotoxic to human MOLT-4 (T cell) (IC50 = 3.0 μM) but non-toxic to MGL-8 (B cell) lymphoblasts. CI-972 is under development as a potential T-cell selective immunosuppressive agent. Synthesis and biological activities of the series are discussed.Keywords
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