# ANALOGS OF 6-VINYLURACIL AS ANTITUMOR AGENTS

> **NIH NIH R01** · MONTEFIORE MEDICAL CENTER (BRONX, NY) · 1988 · $123,648

## Abstract

This program is aimed at the synthesis of several new types of
nucleoside analogs that are expected to be useful as antitumor
agents and enzyme inhibitors, as probes of the conformational
factors involved in the binding of pyrimidines to some of the
enzymes of nucleic acid metabolism, or as antiprotozoal agents.
Specifically, four classes of target nucleosides are proposed.
Classes A and B which contain uridines substituted at C-6 with an
alkene group and 6',6-cyclonucleosides bearing a 6',6-double bond,
are intended to amplify and extend our ongoing work with 6-
vinyluracil and related compounds.  Like the free bases, the
nucleosides are expected to function as alkylating agents, but
their increased solubility and potential for altered distribution
may result in improved antitumor activity.  Target classes C and
D are new to the program but they are related to ongoing work in
that the syntheses to be used are extensions of methods developed
for earlier target compounds.  The cyclonucleosides of class C can
be regarded as conformationally-restricted analogs of ordinary
nucleosides, and they are particularly interesting because the
extended bridge endows them with considerable flexibility.  The
interactions of compounds of type C with pyrimidine-requiring
enzymes could furnish useful information on the range of
substrate conformations acceptable to the particular enzyme
being studied.  Initial studies will be with uridine phosphorylase, in
collaboration with Dr. M. el Kouni at Brown University.

Target compound D - a furopyrimidine C-nucleoside - has recently
been found to be very active against Trypanosoma gambiense.
Since the compound is difficult to prepare, we intend to develop a
new approach that uses methods we have developed in previous
work with 5-hydroxypyrimidines and pyrimidine 5',6-
cyclonucleosides.

In-house studies will be performed to assess biological activities
of target compounds.  The Laboratory of Experimental Antitumor
Testing (Drs. B. Mehta and F. Schmid) will test for activity
against mouse and human tumor cell lines growing in culture, and
active compounds will be further evaluated for in vivo activity in
mice bearing leukemias or solid tumors.

## Key facts

- **NIH application ID:** 3174143
- **Project number:** 7R01CA036517-05
- **Recipient organization:** MONTEFIORE MEDICAL CENTER (BRONX, NY)
- **SAM.gov UEI:** FP1VD1HU5HV7
- **Principal Investigator:** BRIAN A OTTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $123,648
- **Award type:** 7
- **Project period:** 1984-07-01 → 1990-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174143

## Citation

> US National Institutes of Health, RePORTER application 3174143, ANALOGS OF 6-VINYLURACIL AS ANTITUMOR AGENTS (7R01CA036517-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174143. Licensed CC0.

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