ABSTRACT
5,5-Bis(hydroxymethyl)-2-oxo-[1-(2-trifluoromethyl)-3,3,3- trifluoropropionamido)-1-trifluoromethyl-2,2,2-trifluoroethyl- 1,3,2-dioxaphosphan (CA-423) is an in vitro inhibitor of the Escherichia coli uridine and thymidine phosphorylases. Unlike widely studied nucleoside analogues, this compound binds to the enzymes irreversibly. Its LD50 in mice was 40 mg/kg. Due to the involvement of pyrimidine phosphorylases in carcinogenesis and the relatively low toxicity of CA-423, it is promising for anticancer therapy.
Subject(s)
Enzyme Inhibitors/pharmacology , Organophosphorus Compounds/pharmacology , Propionates/pharmacology , Thymidine Phosphorylase/antagonists & inhibitors , Animals , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/toxicity , Escherichia coli/enzymology , Lethal Dose 50 , Magnetic Resonance Spectroscopy , Mice , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/toxicity , Propionates/chemistry , Propionates/toxicityABSTRACT
The conformational analysis of estrone and its derivatives has been performed using the crystallographic data. It is shown that the estrone backbone may have four different conformers due to the conformational flexibility of the B- and D-rings. The correlation plots describing the conformations of the B- and D-rings are given. There is no apparent correlation between the nature of the substituent at C (3) and the overall conformation of the estrone backbone. An X-ray analysis of 3-deoxyestrone has also been undertaken. The crystal data are: space group P212121, Z = 4(C18H22O), a 25,240 (3), b 8,049 (2), c 7,002 (3) A, V 1423 A3, dcalc 1,19 g X cm.-3. The final reliability factors are: R 3,71% and Rw 4,23% for 1501 observed reflections measured on an automatic diffractometer.
