Amino acid derivatives having anti-tumor activity and compositions containing them

#The present invention relates to a series of amino acid amides having anti-tumor activity, many of which are novel compounds, and provides a pharmaceutical composition for the treatment of tumors comprising these amino acid amides, as well as a method of treating tumors and immune deficiencies using them.

#A number of compounds of the amino acid type have been proposed for use as anti-tumor agents. For example, Umezawa et al. [J. Antibiotics 29(8), 857-859 (1976)] disclose a compound called "bestatin", whose systematic name is [(2S, 3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, and which is said to exhibit host-mediated anti-tumor activity; however, the structure of this compound differs markedly from that of the compounds of the present invention. U.S. patent application Ser. No. 597,817, filed Apr. 9, 1984, now U.S. Pat. No. 4,545,942 likewise discloses a series of amino acid derivatives having anti-tumor activities, but again the structure of these compounds is markedly different from that of the compounds of the present invention.

#Compounds which may be represented by the formula: ##STR2## are disclosed in Chemical Abstracts, 98(23) 198680m (1983) (R represents an isopropyl group), Chemical Abstracts, 98(25) 215947Y (1983) (R represents a sec-butyl group) and Chemical Abstracts, 93(15) 150614n (1980) (R represents a benzyl group). Compounds of formula: ##STR3## (in which Z represents a hydrogen atom, a nitro group, a chlorine atom or a methoxy group) are described in Analytical Chemistry, 56, 958-962 (1984). However, it is not disclosed that the compounds of the aforementioned Chemical Abstracts or of the Analytical Chemistry article have any therapeutic activity or value; all of these compounds are disclosed in the context of their use in analytical chemistry or in chemical synthesis.

#In the compounds of the invention, R.sup.1 may represent a benzyl group, a phenyl group, a substituted phenyl group, a naphthyl group, a thienyl group or a pyridyl group. Where R.sup.1 represents a naphthyl group, this may be a 1-naphthyl or 2-naphthyl group. Where R.sup.1 represents a thienyl group, this may be a 2-thienyl or 3-thienyl group, preferably a 2-thienyl group. Where R.sup.1 represents a pyridyl group, this may be a 2-pyridyl, 3-pyridyl or 4-pyridyl group, preferably a 3-pyridyl group.

#Where R.sup.1 represents a substituted phenyl group, it may have 1 or 2 substituents; where it has 1 substituent, this may be at the 2-, 3-, or 4-position; where it has 2 substituents, these may be at the 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-positions. The substituents are selected from the group consisting of C.sub.1 -C.sub.4 alkyl groups, halogen atoms, C.sub.1 -C.sub.4 alkoxy groups, hydroxy groups, carboxy groups, nitro groups, trifluoromethyl groups, amino groups, C.sub.1 -C.sub.4 alkylamino groups, di(C.sub.1 -C.sub.4 alkyl)amino groups, C.sub.1 -C.sub.4 acylamino groups, C.sub.1 -C.sub.4 alkanoyl groups, cyano groups, carbamoyl groups, (C.sub.1 -C.sub.4 alkyl)carbamoyl groups, di(C.sub.1 -C.sub.4 alkyl)carbamoyl groups and C.sub.1 -C.sub.4 alkylthio groups.

#Where the substituent is a C.sub.1 -C.sub.4 alkyl group, this may be a straight or branched chain alkyl group and is more preferably a C.sub.1 -C.sub.3 alkyl group. Examples of such alkyl groups include the methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl and t-butyl groups. Similarly, where the substituent is an alkylamino, dialkylamino, alkylcarbamoyl, dialkylcarbamoyl or alkylthio group, the alkyl group is or the alkyl groups are preferably selected from those exemplified above.