# SYNTHESIS OF ANTITUMOR/VIRAL PYRIMIDINE C-NUCLEOSIDES

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 1991 · $277,271

## Abstract

On the basis of rationale and recent findings in our Laboratory, we plan
to synthesize C-nucleoside derivatives in Figure 1 to study their
biophysical and biochemical nature for eventual applications of cancer-
related chemotherapy.


a) 5'-Hyrogenphosphonate and 5'-methylphosphonate derivatives of 5-
(beta-D-ribofuranosyl)-nicotinamide, 6-(beta-D-
ribofuranosyl)picolinamide, 4-(beta-D-ribofuranosyl)-isonicotinamide and
2-(beta-D-ribofuranosyl)isonicotinamide.  (Class 1).  These analogues
will be studied for their anticancer activity in vitro and in vivo, in
relation to their capacity to inhibit dehydrogenases, especially for the
cancer related enzyme, IMP-dehydrogenase.

b) NAD analogues in which the nicotinamide riboside moiety is displaced
by a ribosylpyridine, and/or the pyrophosphate fragment is displaced by
methylene bis(phosphonate).  (Class 2).  These analogues will be studied
for their and their inhibitory activity against dehydrogenases
(especially cancer related IMP-dehydrogenase), NAD-hydrolases and
poly(ADP-ribose) polymerase.

c) Homo-oligomers of 2'-deoxy-pseudo-isocytidine (c-CdR), 2'-deoxy-9-
deazaadenosine (c-AdR), 2'-deoxy-9-deazaguanosine (c-GdR) and 2'-deoxy-
9-deazainosine (c-IdR).  They are analogues of oligo-dT, -dC, -dA and -
dG respectively (Class 3).  These synthetic homo-oligomers of C-
nucleosides will be studied as to whether they form a double helix with
complementary homo-oligomers of C-nucleotides against nucleases will be
studied.  The physical and biochemical properties of the double helix
will also be studied.

d) Several hetero-oligomers containing a limited amount of C-nucleotides
(Class 4).  These synthetic oligomers will be studied if they form
double helix with complementary oligomers of natural nucleotides.
[e.g., TT...T-cT-TT...T with oligo-A].  The stability of these oligomers
against nucleases will be studied.  The physical and biochemical
stabilities of the double helix will also be studied.

e) Several 5'-di- and tri-phosphates of C-nucleosides to study for
substrate specificity of various polymerizing enzymes (e.g., DNA- and
RNA-polymerases, reverse transcriptases and polynucleotide
phosphorylases).  (Class 5)

f) Large amounts of promising derivatives for further evaluation for
eventual clinical application.

## Key facts

- **NIH application ID:** 3171651
- **Project number:** 2R01CA033907-08A1
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **SAM.gov UEI:** KUKXRCZ6NZC2
- **Principal Investigator:** KYOICHI A WATANABE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $277,271
- **Award type:** 2
- **Project period:** 1983-07-02 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171651

## Citation

> US National Institutes of Health, RePORTER application 3171651, SYNTHESIS OF ANTITUMOR/VIRAL PYRIMIDINE C-NUCLEOSIDES (2R01CA033907-08A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171651. Licensed CC0.

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