1. Field of the Invention
The present invention relates to phosphite-borane derivatives that exhibit antineoplastic, anti-hyperlipidemic, and anti-inflammatory activity.
2. Description of the Related Art
Various boron-containing compounds have previously been shown to exhibit therapeutic biological activity. For example, amine-borane compounds such as amine.degree.BH.sub.2 COOH, amine.degree.BH.sub.2 COOMe and amine.degree.BH.sub.2 CONHR have been demonstrated to exhibit antitumor, anti-inflammatory and hypolipidemic activities. Additionally, phosphite-borane compounds have been used in hydroboration under mild conditions (Pelter, A., et al, J. Chem. Soc. Chem. Commun. (1981), 1014). Since the first reports of phosphite-borane compounds and their properties (Reetz, T., J. Am. Chem. Soc. (1960), 82, 5039), very few phosphite-borane compounds have been synthesized and/or had their properties investigated (Das, M. K., et al, Synth. React. Inorg. Met. Org. Chem. (1986), 16, 67; Martin, D. R. et al; Pennington, B. T., J. Inorg. Nucl. Chem. (1978), 40, 9; and Muttertres, E. L., "The Chemistry of Boron and its Compounds," Wiley, New York, 1967).
Generally, phosphite-borane derivatives may be considered as analogs of alkylphosphates, (RO).sub.3 P.dbd.O vs. (RO).sub.3 PBH.sub.3, as well as analogs of alkylphosphonates, e.g., (RO).sub.2 P(O)CH.sub.3 vs. (RO).sub.2 P(O)BH.sub.3, or (RO).sub.2 P(O)CH.sub.2 X vs. (RO).sub.2 P(O)BH.sub.2 X, wherein R is alkyl and X is halo. Since phosphate and phosphonate groups are present in a variety of biologically important molecules, e.g., DNA, RNA, phospholipids, aminophosphonates, etc., their boron-containing analogs may prove useful as biomolecular probes and as potential therapeutic agents.
Additionally, several synthetic phosphonates, e.g., phosphonoacetic acid, phosphonoformic acid, etc., have been found to possess significant antiviral activity (Mayer, R. F., et al, Antimicrob. Agents Chemother. (1976), 9, 308; Oberg, B., Pharmac. Ther. (1983), 19, 387; and Clerq, E. D., J. Med. Chem. (1986), 29, 1561). This antiviral activity coupled with the established pharmacological activity of amine-borane derivatives makes phosphite-borane derivatives potentially significant as a class of bioactive compounds.
While it is clear that considerable potential exists for the utility of phosphite-borane derivatives as biomolecular probes and therapeutic agents, it is equally clear that not much effort has been focused on exploiting this potential. The present invention arose from our ongoing research into boron analogs of biomolecules potentially useful as probes and therapeutic agents.
It therefore is an object of the present invention to provide new phosphite-borane derivatives including active antineoplastic, anti-hyperlipidemic, and anti-inflammatory agents.
It is another object of the present invention to provide new processes for synthesizing phosphite-borane derivatives exhibiting antineoplastic, anti-hyperlipidemic, and anti-inflammatory activity.
Other objects and advantages will be more fully apparent from the ensuing disclosure and appended claims.
USPTO Backgrounds
USPTO Backgrounds