Hitachi Chemical Company, Ltd.

Nippon Chemiphar Co., Ltd.

Hitachi Chemical Research Center, Inc.

Gabriel F Eilon

John W Jacobs

A method for inducing cell death in neoplastic cells, includes the step of administering a compound of formula I or a pharmaceutically acceptable salt thereof, as a primary chemotherapeutic agent or substantially contemporaneously with chemotherapy, to a patient having multidrug-resistant neoplastic cells, in an amount sufficient to induce cell death in the neoplastic cells: ##STR1## where R.sup.1 is hydroxyl, C1-4 alkoxyl, C1-4 alkylcarboxyloxymethoxyl, phenyl C1-2 alkylamino group, 2,5-pyrrolidinedione-1-alkoxyl (C1-4), or ##STR2## wherein X.sup.1 is a chemical bond or C1-2 alkylene, X.sup.2 is hydrogen or carboxyl forming a 5-membered ring with X.sup.1 when X.sup.1 is methylene, X.sup.3 is hydrogen or C1-2 alkyl, X.sup.4 is hydrogen or C1-2 alkyl, or X.sup.3 and X.sup.4 together form a 5-membered ring, in which at least one of X.sup.2, X.sup.3, and X.sup.4 is hydrogen, R.sup.2 is C3-4 alkyl, R.sup.3 is C1-4 alkyl, ##STR3## in which n is an integer of 0 to 3.

Method for inducing death of neoplastic cells using piperazine

A method for inducing cell death in neoplastic cells, includes the step of administering a compound of formula I or a pharmaceutically acceptable salt thereof, as a primary chemotherapeutic agent or substantially contemporaneously with chemotherapy, to a patient having multidrug-resistant neoplastic cells, in an amount sufficient to induce cell death in the neoplastic cells: ##STR1## where R.sup.1 is hydroxyl, C1-4 alkoxyl, C1-4 alkylcarboxyloxymethoxyl, phenyl C1-2 alkylamino group, 2,5-pyrrolidinedione-1-alkoxyl (C1-4), or ##STR2## wherein X.sup.1 is a chemical bond or C1-2 alkylene, X.sup.2 is hydrogen or carboxyl forming a 5-membered ring with X.sup.1 when X.sup.1 is methylene, X.sup.3 is hydrogen or C1-2 alkyl, X.sup.4 is hydrogen or C1-2 alkyl, or X.sup.3 and X.sup.4 together form a 5-membered ring, in which at least one of X.sup.2, X.sup.3, and X.sup.4 is hydrogen,

A method for inducing cell death in neoplastic cells, includes the step of administering a compound of formula I or a pharmaceutically acceptable salt thereof, as a primary chemotherapeutic agent or substantially contemporaneously with chemotherapy, to a patient having multidrug-resistant neoplastic cells, in an amount sufficient to induce cell death in the neoplastic cells: ##STR1## where R.sup.1 is hydroxyl, C1-4 alkoxyl, C1-4 alkylcarboxyloxymethoxyl, phenyl C1-2 alkylamino group, 2,5-pyrrolidinedione-1-alkoxyl (C1-4), or ##STR2## wherein X.sup.1 is a chemical bond or C1-2 alkylene, X.sup.2 is hydrogen or carboxyl forming a 5-membered ring with X.sup.1 when X.sup.2 is methylene, X.sup.3 is hydrogen or C1-2 alkyl, X.sup.4 is hydrogen or C1-2 alkyl, or X.sup.3 and X.sup.4 together form a 5-membered ring, in which at least one of X.sup.2, X.sup.3, and X.sup.4 is hydrogen,

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Long Beach, CA, United States of America

Gabriel F Eilon