This invention relates to a phenylethyl substituted dimer of ethylene and maleic anhydride and to a method for its complete chemical synthesis without polymerization. This dimer is appropriately named 7-phenyloctane-(1,2),(5,6)-dianhydride.
It is well-known that various polyanionic compounds such as polyacrylic acid, pyran copolymer (divinylether/maleic anhydride) and ethylene/maleic anhydride copolymer (EMA) have antitumor, antiviral and other pharmacological and biological properties. For example, polyanions having the following structural units have been found active against both the solid (intravascular) and ascitic (intraperitoneal) forms of the Walker carcinoma 256 of the rat as determined by the National Cancer Institute: ##STR1## See, for example, Hodnett and Tien Hai Tai, J. Med. Chem. 17 (12), 1335-1337 (1974). The ethylene and succinyl moieties in the above polymeric structure are linked together by the polymerization of ethylene and maleic anhydride.
More recently, it has been shown that certain ammoniated derivatives of such ethylene/maleic anhydride polymers having relatively low molecular weight have enhanced antitumor and immunological activity. See U.S. Pat. Nos. 4,255,537 and 4,309,413. The average molecular weight of these improved polymers ranges from about 300 to about 1500. The smallest component of these polymeric substances having a molecular weight of about 300 is essentially a dimer of ethylene and maleic anhydride.
The previously disclosed method of making the foregoing ethylene/maleic anhydride polymeric compounds of low molecular weight comprises the polymerization of ethylene and maleic anhydride in the presence of alkylated aromatic hydrocarbon having at least one .alpha.-hydrogen. Ethyl benzene is especially preferred. The use of ethyl benzene in the reaction medium results in the introduction of a phenylethyl end group in the polymeric structure. Such end group constitutes a relatively high percentage of the total structure for a polymer of relatively low molecular weight of about 300. The structure of these relatively low molecular weight polymers of ethylene and maleic anhydride having the phenylethyl end group can be represented as follows: ##STR2## See FIG. 1 in Fields et al, J. Med. Chem. 25(9), 1060-1064 (1982), for a report of the above structure. When n in the above formula is equal to one, the polymer would be a phenylethyl substituted dimer having a succinyl anhydride terminal group and a molecular weight of 330.
The EMA type copolymers, including dimers, and their ammoniated derivatives, are also known to be suitable for various non-pharmaceutical uses. Illustrative of such uses is the silver halide dispersion disclosed in U.S. Pat. No. 2,957,767. Other non-pharmaceutical uses of low molecular weight EMA polymers prepared in ethyl benzene solvent are described, for example, in U.S. Pat. No. 2,913,437.
USPTO Backgrounds
USPTO Backgrounds