Synthesis and Antiviral Evaluation of Some Novel Tricyclic Pyrazolo[3,4‐b]indole Nucleosides

Abstract

Novel pyrazolo[3,4‐b]indole nucleoside analogs were synthesized from the corresponding 3‐formyl‐2‐chloroindole and 3‐cyano‐2‐chloroindole nucleosides by treatment with hydrazine. Very few examples of pyrazolo[3,4‐b]indole heterocycles have been published in the literature and this is the first synthesis of nucleoside analogs containing this heterocycle. These new pyrazolo[3,4‐b]indole nucleosides were active against human cytomegalovirus and herpes simplex virus type 1, but this activity was not well separated from cytotoxicity.

^†In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.

Keywords:

• Pyrazolo[3,4‐b]indole
• Nucleoside analogs
• Antiviral

Acknowledgments

We wish to thank Julie M. Breitenbach and Kathy Z. Borysko for expert performance of antiviral and cytotoxicity assays. These studies were supported by training grant T32‐GM07767 and research grant P01‐AI46390 from the National Institutes of Health.

Notes

^†In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.

^aThe pyrazolo[3,4‐b]indoles reported in Ref. 13 were synthesized by a dipolar cycloaddition reaction and may actually be pyrazolo[4,3‐b]indoles.