O.sup.6 -substituted guanine compositions and methods for depleting O.sup.6

A compound of the formula:

• ##STR13## wherein each of X.sub.1 -X.sub.5 is selected from the group consisting of halogen, hydroxy, aryl, a C.sub.1 -C.sub.8 alkyl substituted aryl, nitro, a polycyclic aromatic alkyl containing 2-4 aromatic rings wherein the alkyl is a C.sub.1 -C.sub.6, a C.sub.3 -C.sub.8 cycloalkyl, a C.sub.2 -C.sub.6 alkenyl, a C.sub.2 -C.sub.6 alkynyl, a C.sub.1 -C.sub.6 hydroxyalkyl, a C.sub.1 -C.sub.8 alkoxy, a C.sub.2 -C.sub.8 alkoxyalkyl, aryloxy, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, amino, a monoalkylamino wherein the alkyl is C.sub.1 -C.sub.6, a dialkylamino wherein the alkyl is C.sub.1 -C.sub.6, acylamino, ureido, thioureido, carboxy, a carboxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, cyano, a cyanoalkyl wherein the alkyl is C.sub.1 -C.sub.6, C-formyl, C-acyl, a dialkoxymethyl wherein the alkoxy is C.sub.1 -C.sub.6, an aminoalkyl wherein the alkyl is C.sub.1 -C.sub.6, and SO.sub.n R.sub.1 wherein n=0, 1, 2 or 3, R.sub.1 is H, a C.sub.1 -C.sub.6 alkyl or aryl;
• and
• wherein Z is selected from the group consisting of methyl, aryl, a substituted aryl wherein the aryl substituents are selected from the group consisting of C.sub.1 -C.sub.6 alkyls, nitro and halo, a polycyclic aromatic alkyl containing 2-4 aromatic rings, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.6 alkynyl, halomethyl, C.sub.3 -C.sub.6 haloalkyl, C.sub.1 -C.sub.3 hydroxyalkyl, C.sub.1 -C.sub.6 halohydroxy alkyl, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.3, carboxy, the acid and salt forms of carboxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, C.sub.1 -C.sub.8 alkoxy, carbonyl, carbamoyl, a carbamoylalkyl wherein the alkyl is C.sub.1 -C.sub.6, hydrazinocarbonyl, chlorocarbonyl, cyano, C.sub.2 -C.sub.9 cyanoalkyl, C-formyl, a dialkoxymethyl wherein the alkoxy is C.sub.1 -C.sub.6, C-acyl, an alkoxy hydroxyalkyl wherein the alkyl and the alkoxy are C.sub.1 -C.sub.4, carboxymethyl thio, a carboalkoxy alkyl wherein the alkoxy and alkyl are C.sub.1 -C.sub.6, a monoalkylamino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, a dialkylamino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, amino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, a peptide, a monosaccharide selected from the group consisting of aldotetroses and aldohexoses, a polysaccharide selected from the group consisting of sucrose, lactose, maltose and cellobiose, a nucleic acid segment, asteroid selected from the group consisting of testosterone, nortestosterone, and dihydrotestosterone, and SO.sub.n R.sub.1 wherein n is 0, 1, 2, or 3 and R.sub.1 is H, C.sub.1 -C.sub.6 alkyl or aryl.

A pharmaceutical composition comprising a compound of the formula:

• ##STR14## wherein each of X.sub.1 -X.sub.5 is selected from the group consisting of hydrogen, halogen, hydroxy, aryl, a C.sub.1 -C.sub.8 alkyl substituted aryl, nitro, a polycyclic aromatic alkyl containing 2-4 aromatic rings wherein the alkyl is a C.sub.1 -C.sub.6, a C.sub.3 -C.sub.8 cycloalkyl, a C.sub.2 -C.sub.6 alkenyl, a C.sub.2 -C.sub.6 alkynyl, a C.sub.1 -C.sub.6 hydroxyalkyl, a C.sub.1 -C.sub.8 alkoxy, a C.sub.2 -C.sub.8 alkoxyalkyl, aryloxy, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, amino, a monoalkylamino wherein the alkyl is C.sub.1 -C.sub.6, a dialkylamino wherein the alkyl is C.sub.1 -C.sub.6, acrylamino, ureido, thioureido, carboxy, a carboxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, cyano, a cyanoalkyl wherein the alkyl is C.sub.1 -C.sub.6, C-formyl, C-acyl, a dialkoxymethyl wherein the alkoxy is C.sub.1 -C.sub.6, an aminoalkyl wherein the alkyl is C.sub.1 -C.sub.6, and SO.sub.n R.sub.1 wherein n=0, 1, 2, or 3, R.sub.1 is H, a C.sub.1 -C.sub.6 alkyl or aryl;
• and
• wherein Z is selected from the group consisting of methyl, aryl, a substituted aryl wherein the aryl substitutents are selected from the group consisting of C.sub.1 -C.sub.6 alkyls, nitro and halo, a polycyclic aromatic alkyl containing 2-4 aromatic rings, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.6 alkynyl, halomethyl, C.sub.3 -C.sub.6 haloalkyl, C.sub.1 -C.sub.3 hydroxyalkyl, C.sub.1 -C.sub.6 halohydroxy alkyl, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.3, carboxy, the acid and salt forms of carboxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, C.sub.1 -C.sub.8 alkoxy, carbonyl, carbamoyl, a carbamoylalkyl wherein the alkyl is C.sub.1 -C.sub.6, hydrazinocarbonyl, a carbamoylalkyl wherein the alkyl is C.sub.1 -C.sub.6, hydrazinocarbonyl, chlorocarbonyl, cyano, C.sub.2 -C.sub.9 cyanoalkyl, C-formyl, a dialkoxymethyl wherein the alkoxy is C.sub.1 -C.sub.6, C-acyl, an alkoxy hydroxyalkyl wherein the alkyl and the alkoxy are C.sub.1 -C.sub.4, carboxymethyl thio, a carboalkoxy alkyl wherein the alkoxy and alkyl are C.sub.1 -C.sub.6, a monoalkylamino hydroxylalkyl wherein the alkyl is C.sub.1 -C.sub.6, a dialkylamino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, amino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, a peptide, a monosaccharide selected from the group consisting of aldotetroses and aldohexoses, a polysaccharide selected from the group consisting of sucrose, lactose, maltose and cellobiose, a nucleic acid segment, a steroid selected from the group consisting of testosterone, nortestosterone, and dihydrotestosterone, and SO.sub.n R.sub.1 wherein n is 0, 1, 2, or 3 and R.sub.1 is H, C.sub.1 -C.sub.6 alkyl or aryl, and a pharmaceutically acceptable excipient.

A compound of the formula:

• ##STR18## wherein each of X.sub.1 -C.sub.5 is selected from the group consisting of hydroxy, aryl, a C.sub.1 -C.sub.8 alkyl substituted aryl, a polycyclic aromatic alkyl containing 2-4 aromatic rings wherein the alkyl is a C.sub.1 -C.sub.6, a C.sub.3 -C.sub.8 cycloalkyl, a C.sub.2 -C.sub.6 alkenyl, a C.sub.2 -C.sub.6 alkynyl, a C.sub.1 -C.sub.6 hydroxyalkyl, a C.sub.2 -C.sub.8 alkoxyalkyl, aryloxy, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, amino, a monoalkylamino wherein the alkyl is C.sub.1 -C.sub.6, a dialkylamino wherein the alkyl is C.sub.1 -C.sub.6, acylamino, ureido, thioureido, carboxy, a carboxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, cyano, a cyanoalkyl wherein the alkyl is C.sub.1 -C.sub.6, C-formyl, C-acyl, a dialkoxyethyl wherein the alkoxy is C.sub.1 -C.sub.6, an aminoalkyl wherein the alkyl is C.sub.1 -C.sub.6, and SO.sub.n R.sub.1 wherein n=0, 1, 2 or 3, R.sub.1 is H, a C.sub.1 -C.sub.6 alkyl or aryl;
• and
• wherein Z is selected from the group consisting of aryl, a substituted aryl wherein the aryl substituents are selected from the group consisting of C.sub.1 -C.sub.6 alkyls, nitro and halo, a polycyclic aromatic alkyl containing 2-4 aromatic rings, C.sub.2 -C.sub.6 alkenyl, C.sub.6 alkynyl, halomethyl, C.sub.1 -C.sub.3 hydroxyalkyl, C.sub.1 -C.sub.6 halohydroxy alkyl, acyloxy, pivaloyloxyethyl, carboxy, the acid and salt forms of carboxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, C.sub.1 -C.sub.8 alkoxy, carbonyl, carboyl, a carbamoylalkyl wherein the alkyl is C.sub.1 -C.sub.6, hydrazinocarbonyl, chlorocarbonyl, cyano, C.sub.2 -C.sub.9 cyanoalkyl, C-formyl, a dialkoxyethyl wherein the alkoxy is C.sub.1 -C.sub.6, C-acyl, an alkoxy hydroxyalkyl wherein the alkyl and the alkoxy are C.sub.1 -C.sub.4, carboxyethyl thio, a carboalkoxy alkyl wherein the alkoxy and alkyl are C.sub.1 -C.sub.6, a monoalkylamino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, a dialkylamino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, amino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, a peptide, a monosaccharide selected from the group consisting of aldotetroses, aldopentoses and aldohexoses, a polysaccharide selected from the group consisting of sucrose, lactose, maltose and cellobiose, a nucleic acid segment, asteroid selected from the group consisting of testosterone, nortestosterone, and dihydrotestosterone, and SO.sub.n R.sub.1 wherein n is 0, 1, 2, or 3 and R.sub.1 is H, C.sub.1 -C.sub.6 alkyl or aryl.

A compound of the formula:

• ##STR20## wherein each of X.sub.1 -X.sub.5 is selected from the group consisting of hydroxy, aryl, a C.sub.1 -C.sub.8 alkyl substituted aryl, a polycyclic aromatic alkyl containing 2-4 aromatic rings wherein the alkyl is a C.sub.1 -C.sub.6, a C.sub.3 -C.sub.8 cycloalkyl, a C.sub.2 -C.sub.6 alkenyl, a C.sub.2 -C.sub.6 alkynyl, a C.sub.1 -C.sub.6 hydroxyalkyl, a C.sub.1 -C.sub.8 alkoxy, a C.sub.2 -C.sub.8 alkoxyalkyl, aryloxy, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, amino, a monoalkylamino wherein the alkyl is C.sub.1 -C.sub.6, a dialkylamino wherein the alkyl is C.sub.1 -C.sub.6, acylamino, ureido, thioureido, carboxy, a carboxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, cyano, a cyanoalkyl wherein the alkyl is C.sub.1 -C.sub.6, C-formyl, C-acyl, a dialkoxymethyl wherein the alkoxy is C.sub.1 -C.sub.6, an aminoalkyl wherein the alkyl is C.sub.1 -C.sub.6, and SO.sub.n R.sub.1 wherein n=0, 1, 2 or 3, R.sub.1 is H, a C.sub.1 -C.sub.6 alkyl or aryl;
• and
• wherein Z is selected from the group consisting of methyl, aryl, a substituted aryl wherein the aryl substituents are selected from the group consisting of C.sub.1 -C.sub.6 alkyls, nitro and halo, a polycyclic aromatic alkyl containing 2-4 aromatic rings, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.6 alkynyl, halomethyl, C.sub.3 -C.sub.6 haloalkyl, C.sub.1 -C.sub.3 hydroxyalkyl, C.sub.1 -C.sub.6 halohydroxy alkyl, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.3, carboxy, the acid and salt forms of carboxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, C.sub.1 -C.sub.8 alkoxy, carbonyl, carbamoyl, a carbamoylalkyl wherein the alkyl is C.sub.1 -C.sub.6, hydrazinocarbonyl, chlorocarbonyl, cyano, C.sub.2 -C.sub.9 cyanoalkyl, C-formyl, a dialkoxymethyl wherein the alkoxy is C.sub.1 -C.sub.6, C-acyl, an alkoxy hydroxyalkyl wherein the alkyl and the alkoxy are C.sub.1 -C.sub.4, carboxymethyl thio, a carboalkoxy alkyl wherein the alkoxy and alkyl are C.sub.1 -C.sub.6, a monoalkylamino hydroxylalkyl wherein the alkyl is C.sub.1 -C.sub.6, a dialkylamino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, amino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, a peptide, a monosaccharide selected from the group consisting of aldotetroses, aldopentoses and aldohexoses, a polysaccharide selected from the group consisting of sucrose, lactose, maltose and cellobiose, a nucleic acid segment, asteroid selected from the group consisting of testosterone, nortestosterone, and dihydrotestosterone, and SO.sub.n R.sub.1 wherein n is 0, 1, 2, or 3 and R.sub.1 is H, C.sub.1 -C.sub.6 alkyl or aryl.

A method for treating tumor cells in a host which comprises administering to the host an amount effective to reduce AGT activity in the host of a compound selected from the group consisting of (a) a compound of the formula:

• ##STR21## wherein X.sub.1 -X.sub.5 are selected from the group consisting of hydrogen, halogen, hydroxy, aryl, a C.sub.1 -C.sub.8 alkyl substituted aryl, nitro, a polycyclic aromatic alkyl containing 2-4 aromatic rings wherein the alkyl is a C.sub.1 -C.sub.6, a C.sub.3 -C.sub.8 cycloalkyl, a C.sub.2 -C.sub.6 alkenyl, a C.sub.2 -C.sub.6 alkynyl, a C.sub.1 -C.sub.6 hydroxyalkyl, a C.sub.1 -C.sub.8 alkoxy, a C.sub.2 -C.sub.8 alkoxyalkyl, aryloxy, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, amino, a monoalkylamino wherein the alkyl is C.sub.1 -C.sub.6, a dialkylamino wherein the alkyl is C.sub.1 -C.sub.6, acylamino, ureido, thioureido, carboxy, a carboxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, cyano, a cyanoalkyl wherein the alkyl is C.sub.1 -C.sub.6, C-formyl, C-acyl, a dialkoxymethyl wherein the alkoxy is C.sub.1 -C.sub.6, an aminoalkyl wherein the alkyl is C.sub.1 -C.sub.6, and SO.sub.n R.sub.1 wherein n=0, 1, 2 or 3, R.sub.1 is H, a C.sub.1 -C.sub.6 alkyl or aryl;
• and
• wherein Z is selected from the group consisting of methyl, aryl, a substituted aryl wherein the aryl substituents are selected from the group consisting of C.sub.1 -C.sub.6 alkyls, nitro and halo, a polycyclic aromatic alkyl containing 2-4 aromatic rings, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.6 alkynyl, halomethyl, C.sub.3 -C.sub.6 haloalkyl, C.sub.1 -C.sub.3 hydroxyalkyl, C.sub.1 -C.sub.6 halohydroxy alkyl, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.3, carboxy, the acid and salt forms of carboxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, C.sub.1 -C.sub.8 alkoxy, carbonyl, carbamoyl, a carbamoylalkyl wherein the alkyl is C.sub.1 -C.sub.6, hydrazinocarbonyl, chlorocarbonyl, cyano, C.sub.2 -C.sub.9 cyanoalkyl, C-formyl, a dialkoxymethyl wherein the alkoxy is C.sub.1 -C.sub.6, C-acyl, an alkoxy hydroxyalkyl wherein the alkyl and the alkoxy are C.sub.1 -C.sub.4, carboxymethyl thio, a carboalkoxy alkyl wherein the alkoxy and alkyl are C.sub.1 -C.sub.6, a monoalkylamino hydroxylalkyl wherein the alkyl is C.sub.1 -C.sub.6, a dialkylamino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, amino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, a peptide, a monosaccharide selected from the group consisting of aldotetroses, aldopentoses and aldohexoses, a polysaccharide selected from the group consisting of sucrose, lactose, maltose and cellobiose, a nucleic acid segment selected from the group consisting of 5'-d(AACAGCCATATG.sup.* GCCC)-3', 5'-d(GTGGGCGCTG.sup.* GAGGCG)-3', 5'-d(GTGGGCGCTGG.sup.* GAGGCG)-3', and 5'-d(GTGGGCGCTG.sup.* G.sup.* AGGCG)-3' wherein G.sup.* is O.sup.6 -benzyl-2'-deoxyguanosine residue, a steroid selected from the group consisting of testosterone, nortestosterone, and dihydrotestosterone, and SO.sub.n R.sub.1 wherein n is 0, 1, 2, or 3 and R.sub.1 is H, C.sub.1 -C.sub.6 alkyl or aryl;
• (b) a compound of the formula:
• ##STR22## wherein each of X.sub.1 -X.sub.5 is selected from the group consisting of C.sub.2 -C.sub.8 alkoxyalkyl, aryloxy, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.3, hydrazino, hydroxyamino, acylamino, or nitro at o and m-positions, m-methyl, C.sub.1 -C.sub.4 hydroxy alkyl, C.sub.2 -C.sub.6 alkyl, C-formyl, and aryl;
• (c) a compound of the formula:
• ##STR23## wherein Z is 1-.beta.-D-ribofuranoside or 1-.beta.-D-2-deoxy ribofuranoside and wherein each of X.sub.1 -X.sub.5 is selected from the group consisting of C.sub.2 -C.sub.8 alkoxyalkyl, aryloxy, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, acylamino, and nitro;
• (d) a compound of the formula:
• ##STR24## wherein Z is carboethoxymethyl, a conjugate acid form of a carboxymethyl group, a carboxylate anion of a carboxymethyl group as sodium salt, carbamoyl methyl, 2-hydroxybutyl, cyanomethyl, pivaloyloxymethyl, 3-amino-2-hydroxypropyl, 3-alkylamino-2-hydroxypropyl, or 3-dialkylamino-2-hydroxypropyl;
• (e) a compound represented by the formula ##STR25## wherein each of X.sub.1 -X.sub.5 is selected from the group consisting of halogen, nitro, phenyl, C.sub.1 -C.sub.4 alkyl substituted phenyl, a C.sub.1 -C.sub.4 alkyl, a C.sub.1 -C.sub.4 alkoxy, a C.sub.2 -C.sub.4 alkenyl, a C.sub.2 -C.sub.4 alkynyl, an amino, a C.sub.1 -C.sub.4 monoalkylamino, a C.sub.1 -C.sub.4 dialkylamino, a trifluoromethyl, hydroxy, hydroxymethyl, and SO.sub.n R.sub.1 wherein n is 0, 1, 2, or 3 and R.sub.1 is hydrogen, a C.sub.1 -C.sub.4 alkyl, phenyl, or a C.sub.1 -C.sub.4 alkyl substituted phenyl;
• and
• (f) a compound of the formula ##STR26## wherein Z is 1-.beta.-D-riobofuranoside or 1-.beta.-D-2-deoxy-riobofuranoside, and X.sub.1 -X.sub.5 is each selected from the group consisting of halogen, nitro, phenyl, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, amino, C.sub.1 -C.sub.4 monoalkylamino, C.sub.1 -C.sub.4 dialkylamino, trifluoromethyl, hydroxy, hydroxymethyl, and SO.sub.n R.sub.1 wherein n is 0, 1, 2, or 3, and R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkyl, or phenyl.

A method of enhancing the chemotherapeutic treatment of tumor cells in a host comprising

• administering to the host a chemotherapeutic treatment amount of an O.sup.6 -substituted guanine compound selected from the group consisting of (a) a compound of of the formula:
• ##STR27## wherein each of X.sub.1 -X.sub.5 is selected from the group consisting of hydrogen, halogen, hydroxy, aryl, a C.sub.1 -C.sub.8 alkyl substituted aryl, nitro, a polycyclic aromatic alkyl containing 2-4 aromatic rings wherein the alkyl is a C.sub.1 -C.sub.6, a C.sub.3 -C.sub.8 cycloalkyl, a C.sub.2 -C.sub.6 alkenyl, a C.sub.2 -C.sub.6 alkynyl, a C.sub.1 -C.sub.6 hydroxyalkyl, a C.sub.1 -C.sub.8 alkoxy, a C.sub.2 -C.sub.8 alkoxyalkyl, aryloxy, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, amino, a monoalkylamino wherein the alkyl is C.sub.1 -C.sub.6, a dialkylamino wherein the alkyl is C.sub.1 -C.sub.6, acylamino, ureido, thioureido, carboxy, a carboxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, cyano, a cyanoalkyl wherein the alkyl is C.sub.1 -C.sub.6, C-formyl, C-acyl, a dialkoxymethyl wherein the alkoxy is C.sub.1 -C.sub.6, an aminoalkyl wherein the alkyl is C.sub.1 -C.sub.6, and SO.sub.n R.sub.1 wherein n=0, 1, 2 or 3, R.sub.1 is H, a C.sub.1 -C.sub.6 alkyl or aryl;
• and
• wherein Z is selected from the group consisting of methyl, aryl, a substituted aryl wherein the aryl substituents are selected from the group consisting of C.sub.1 -C.sub.6 alkyls, nitro and halo, a polycyclic aromatic alkyl containing 2-4 aromatic rings, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.6 alkynyl, halomethyl, C.sub.3 -C.sub.6 haloalkyl, C.sub.1 -C.sub.3 hydroxyalkyl, C.sub.1 -C.sub.6 halohydroxy alkyl, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.3, carboxy, the acid and salt forms of carboxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, C.sub.1 -C.sub.8 alkoxy, carbonyl, carbamoyl, a carbamoylalkyl wherein the alkyl is C.sub.1 -C.sub.6, hydrazinocarbonyl, chlorocarbonyl, cyano, C.sub.2 -C.sub.9 cyanoalkyl, C-formyl, a dialkoxymethyl wherein the alkoxy is C.sub.1 -C.sub.6, C-acyl, an alkoxy hydroxyalkyl wherein the alkyl and the alkoxy are C.sub.1 -C.sub.4, carboxymethyl thio, a carboalkoxy alkyl wherein the alkoxy and alkyl are C.sub.1 -C.sub.6, a monoalkylamino hydroxylalkyl wherein the alkyl is C.sub.1 -C.sub.6, a dialkylamino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, amino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, a peptide, a monosaccharide selected from the group consisting of aldotetroses, aldopentoses and aldohexoses, a polysaccharide selected from the group consisting of sucrose, lactose, maltose and cellobiose, a nucleic acid segment selected from the group consisting of 5'-d(AACAGCCATATG.sup.* GCCC)-3', 5'-d(GTGGGCGCTG.sup.* GAGGCG)-3', 5'-d(GTGGGCGCTGG.sup.* GAGGCG)-3', and 5'-(GTGGGCGCTG.sup.* G.sup.* AGGCG)-3' wherein G.sup.* is O.sup.6 -benzyl 2-deoxyguanosine residue, a steroid selected from the group consisting of testosterone, nortestosterone, and dihydrotestosterone, and SO.sub.n R.sub.1 wherein n is 0, 1, 2, or 3 and R.sub.1 is H, C.sub.1 -C.sub.6 alkyl or aryl;
• (b) a compound of the formula:
• ##STR28## wherein each of X.sub.1 -X.sub.5 is selected from the group consisting of C.sub.2 -C.sub.8 alkoxyalkyl, aryloxy, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.3, hydrazino, hydroxyamino, acylamino, or nitro at o and m-positions, m-methyl, C.sub.1 -C.sub.3 hydroxy alkyl, C.sub.2 -C.sub.6 alkyl, C-formyl, and aryl;
• (c) a compound of of the formula:
• ##STR29## wherein Z is 1-.beta.-D-ribofuranoside or 1-.beta.-D-2-deoxy ribofuranoside and wherein each of X.sub.1 -X.sub.5 is selected from the group consisting of C.sub.2 -C.sub.8 alkoxyalkyl, aryloxy, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, acylamino, and nitro.
• (d) a compound of the formula:
• ##STR30## wherein Z is carboethoxymethyl, a conjugate acid form of a carboxymethyl group, a carboxylate anion of a carboxymethyl group as sodium salt, carbamoyl methyl, 2-hydroxybutyl, cyanomethyl, pivaloyloxymethyl, 3-amino-2-hydroxypropyl, 3-alkylamino-2-hydroxypropyl, and 3-dialkylamino-2-hydroxypropyl;
• (e) a compound represented by the formula ##STR31## wherein each of X.sub.1 -X.sub.5 is selected from the group consisting of halogen, nitro, phenyl, C.sub.1 -C.sub.4 alkyl substituted phenyl, a C.sub.1 -C.sub.4 alkyl, a C.sub.1 -C.sub.4 alkoxy, a C.sub.2 -C.sub.4 alkenyl, a C.sub.2 -C.sub.4 alkynyl, an amino, a C.sub.1 -C.sub.4 monoalkylamino, a C.sub.1 -C.sub.4 dialkylamino, a trifluoromethyl, hydroxy, hydroxymethyl, and SO.sub.n R.sub.1 wherein n is 0, 1, 2, or 3 and R.sub.1 is hydrogen, a C.sub.1 -C.sub.4 alkyl, phenyl, or a C.sub.1 -C.sub.4 alkyl substituted phenyl;
• and
• (f) a compound of the formula ##STR32## wherein Z is 1-.beta.-D-riobofuranoside or 1-.beta.-D-2-deoxy-riobofuranoside, and X.sub.1 -X.sub.5 is each selected from the group consisting of halogen, nitro, phenyl, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, amino, C.sub.1 -C.sub.4 monoalkylamino, C.sub.1 -C.sub.4 dialkylamino, trifluoromethyl, hydroxy, hydroxymethyl, and SO.sub.n R.sub.1 wherein n is 0, 1, 2, or 3, and R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkyl, or phenyl, and an anti-neoplastic alkylating agent whose mechanism of action involves modification of the O.sup.6 position of DNA-guanine residue.

A compound of the formula:

• ##STR39## wherein each of X.sub.1 -X.sub.5 is selected from the group consisting of hydroxy, aryl, a C.sub.1 -C.sub.8 alkyl substituted aryl, a polycyclic aromatic alkyl containing 2-4 aromatic rings wherein the alkyl is a C.sub.1 -C.sub.6, a C.sub.3 -C.sub.8 cycloalkyl, a C.sub.2 -C.sub.6 alkenyl, a C.sub.2 -C.sub.6 alkynyl, a C.sub.1 -C.sub.6 hydroxyalkyl, a C.sub.1 -C.sub.8 alkoxy, a C.sub.2 -C.sub.8 alkoxyalkyl, aryloxy, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, amino, a monoalkylamino wherein the alkyl is C.sub.1 -C.sub.6, a dialkylamino wherein the alkyl is C.sub.1 -C.sub.6, acylamino, ureido, thioureido, carboxy, a carboxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, cyano, a cyanoalkyl wherein the alkyl is C.sub.1 -C.sub.6, C-formyl, C-acyl, a dialkoxymethyl wherein the alkoxy is C.sub.1 -C.sub.6, an aminoalkyl wherein the alkyl is C.sub.1 -C.sub.6, and SO.sub.n R.sub.1 wherein n=0, 1, 2 or 3, R.sub.1 is H, a C.sub.1 -C.sub.6 alkyl or aryl;
• and
• wherein Z is selected from the group consisting of methyl, aryl, a substituted aryl wherein the aryl substituents are selected from the group consisting of C.sub.1 -C.sub.6 alkyls, nitro and halo, a polycyclic aromatic alkyl containing 2-4 aromatic rings, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.6 alkynyl, halomethyl, C.sub.3 -C.sub.6 haloalkyl, C.sub.1 -C.sub.3 hydroxyalkyl, C.sub.1 -C.sub.6 halohydroxy alkyl, acyloxy, an acyloxyalkyl wherein the alkyl is C.sub.1 -C.sub.3, carboxy, the acid and salt forms of carboxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, C.sub.1 -C.sub.8 alkoxy, carbonyl, carbamoyl, a carbamoylalkyl wherein the alkyl is C.sub.1 -C.sub.6, hydrazinocarbonyl, chlorocarbonyl, cyano, C.sub.2 -C.sub.9 cyanoalkyl, C-formyl, a dialkoxymethyl wherein the alkoxy is C.sub.1 -C.sub.6, C-acyl, an alkoxy hydroxyalkyl wherein the alkyl and the alkoxy are C.sub.1 -C.sub.4, carboxymethyl thio, a carboalkoxy alkyl wherein the alkoxy and alkyl are C.sub.1 -C.sub.6, a monoalkylamino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, a dialkylamino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, amino hydroxyalkyl wherein the alkyl is C.sub.1 -C.sub.6, a peptide, a monosaccharide selected from the group consisting of aldotetroses, aldopentoses, and aldohexoses, a polysaccharide selected from the group consisting of sucrose, lactose, maltose and cellobiose, a nucleic acid segment, asteroid selected from the group consisting of testosterone, nortestosterone, and dihydrotestosterone, and SO.sub.n R.sub.1 wherein n is 0, 1, 2, or 3 and R.sub.1 is H, C.sub.1 -C.sub.6 alkyl or aryl.