Synthesis and biological activities of 5-trifluoromethyl-5'-azido-2',5'-dideoxyuridine and 5-trifluoromethyl-5'-amino-2',5'-dideoxyuridine
5-Trifluoromethyl-2'-deoxyuridine (1) was tosylated with p-toluenesulfonyl chloride in dry pyridine at 3/sup 0/ to give 5-trifluoromethyl-5'-O-(p-tolylsulfonyl)-2'-deoxyuridine (2), which was converted to 5-trifluoromethyl-5'-azido-2',5'-dideoxyuridine (3) by reacting with lithium azide in N,N-dimethylformamide at 85-90/sup 0/ for 2 h. Compound 3 was then hydrogenated in ethanol-water (1 : 1, v/v) at room temperature and 35 psi of hydrogen pressure, using 10% palladium on charcoal as catalyst, to yield 5-trifluoromethyl-5'-amino-2',5'-dideoxyuridine (4). Compound 4 is about fourfold less potent than compound 1 as an antiviral agent but is about 40-fold less toxic to the host Vero cells. Thus the therapeutic index of compound 1 has been improved by a factor of 10 by replacement of the 5'-hydroxyl with an amino group. Compound 1, however, is more than 100-fold more inhibitory to Sarcoma 180 cells in culture relative to compound 4. Compound 3 is markedly less potent than compound 1 or 4 as either an antiviral or an antineoplastic compound. 2 figures, 1 table, 16 references.
- Research Organization:
- Yale Univ., New Haven
- OSTI ID:
- 6760035
- Journal Information:
- J. Med. Chem.; (United States), Journal Name: J. Med. Chem.; (United States) Vol. 19:7; ISSN JMCMA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
400301* -- Organic Chemistry-- Chemical & Physicochemical Properties-- (-1987)
550200 -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
ALKALI METAL COMPOUNDS
AMIDES
AMINES
AROMATICS
AZIDES
AZINES
CATALYSTS
CATALYTIC EFFECTS
CHEMICAL REACTION YIELD
CHEMICAL REACTIONS
CHLORIDES
CHLORINE COMPOUNDS
CRYOGENIC FLUIDS
DEOXYURIDINE
DRUGS
ELEMENTS
ETHANOL
FLUIDS
HALIDES
HALOGEN COMPOUNDS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROGEN
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
LITHIUM COMPOUNDS
MEDIUM PRESSURE
MEDIUM TEMPERATURE
METALS
NITROGEN COMPOUNDS
NONMETALS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXYGEN COMPOUNDS
PALLADIUM
PLATINUM METALS
PRESSURE DEPENDENCE
PYRIDINE
PYRIDINES
PYRIMIDINES
RIBOSIDES
TEMPERATURE DEPENDENCE
TOLUENE
TRANSITION ELEMENTS
URACILS
WATER
YIELDS