Yale University

Krishnamurthy Shyam

Alan C Sartorelli

Philip G Penketh

Alan A Divo

Robert T Hrubiec

Shu-Hui Chen

The present invention relates to a compound of the formula wherein R.sup.1 and R.sup.2 are selected from lower alkyl groups having 1-6 carbon atoms, substituted or unsubstituted aryl groups, and unsaturated alkyl groups having 1-6 carbon atoms; R.sup.3 is a substituted or unsubstituted lower alkyl group having 1-6 carbons; and R.sup.4 is selected from substituted or unsubstituted lower alkyl groups having 1-6 carbon atoms, substituted or unsubstituted aryl groups, and unsaturated alkyl groups having 1-6 carbon atoms. The present invention also relates to a pharmaceutical composition comprising the above compound, as well as a method of treating tumor cells with the compound.

N,n-bis(sulfonyl)hydrazines useful as antineoplastic agents

The present invention relates to novel 2-aminocarbonyl-1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazines and 2-aminocarbonyl-1,2-bis(methylsulfonyl)-1-methylhydrazines, and their use to treat malignant tumors. The agents are especially useful in the treatment of animal and human cancers. Two preferred agents in this class, especially for use in the treatment of tumors are 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-(2-chloroethyl)aminocarbonylhy drazine and 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-methylaminocarbonylhydrazine. These agents are characterized by the following: they are incapable of undergoing inactivation by the denitrosation mechanism proposed for the inactivation of the CNUs; they are incapable of generating a hydroxyethylating species by the mechanism proposed for the CNUs; and they are capable of chloroethylation or methylation and carbamoylation.

Antitumor 2-aminocarbonyl-1,

Novel antineoplastic 1-alkyl-2-acyl-1,2-disulfonylhydrazine having the following formula and methods of therapy using those antineoplastic compounds: ##STR1## where R.sub.1 and R.sub.2 are (independently) alkyl, cycloalkyl, aryl, aralkyl or heteroaryl. X is an acyl group, and Z is an alkyl or a haloalkyl group.

1-alkyl-2-acyl-1,2-disulfonylhydrazines

Sulfonylhydrazines of the formula RSO.sub.2 N(CH.sub.2 CH.sub.2 X)N(SO.sub.2 CH.sub.3).sub.2, wherein R is an alkyl or an aryl and X is a halogen or OSO.sub.2 Y, wherein Y is an alkyl or an aryl. Such sulfonylhydrazines are useful in treating cancer. Methylating agents of the formula

Sulfonylhydrazines and their use as antineoplastic agents and as

Compounds of the formula: ##STR1## wherein R.sub.1 is a lower alkyl of 1-6 carbon atoms, benzyl, phenyl or phenyl substituted by halogen, alkoxy of 1 to 4 carbon atoms, alkyl of 1 to 4 carbon atoms, amino, or carbonyl substitutents, or --RN(R').sub.2 wherein R and R' are each independently alkyl of 1 to 4 carbon atoms; R.sub.2 is an aromatic substituent, and each A is an aromatic substitution indpendently selected from the group consisting of hydrogen, alkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, halogen, --NO.sub.2, --NH.sub.2,--COOH, and --NHCOCH.sub.3. The compounds have been found to be alkylating agents having antineoplastic activity for use in inhibiting the growth of tumors.

1-alkyl-1-sulfonyl-2-alkoxycarbonylsulfenylhydrazines having

Compounds of the formula ##STR1## where R is methyl or 2-chloroethyl, and R.sup.1 and R.sup.2 are each an aromatic hydrocarbon, ring substituted aromatic hydrocarbon moiety, or an alkyl moiety. The compounds have been found to be alkylating agents having antineoplastic activity.

N,N'-bis(sulfonyl)hydrazines having antineoplastic activity

Compounds of the formula: ##STR1## wherein R.sub.1 s an alkyl of 1-6 carbon atoms, benzyl, phenyl, or phenyl substituted by halogen, alkoxy of 1 to 4 carbon atoms, alkyl of 1 to 4 carbon atoms, amino, or carbonyl substituents, or --RN(R').sub.2 wherein R and R' are each independently an alkyl of 1 to 4 carbon atoms; R.sub.2 is an aromatic substituent selected from the group consisting of phenyl, benzyl, and naphthyl, and A is an aromatic substitution selected from the group consisting of hydrogen, alkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, halogen, --NO.sub.2, --NH.sub.2, --COOH, and --NHCOCH.sub.3. The compounds have been found to be alkylating agents having antineoplastic activity for use in inhibiting the growth of tumors.

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Hamden, CT, United States of America

Krishnamurthy Shyam