Studies on the mechanism of decomposition and structural factors affecting the aqueous stability of 1,2-bis(sulfonyl)-1-alkylhydrazines.
1,2-Bis(sulfonyl)-1-alkylhydrazines are highly active experimental antineoplastic agents which decompose with first-order kinetics in neutral aqueous solutions. These agents generate approximately 2 mol of the corresponding sulfinate, 1 mol of nitrogen, and 1 mol of the appropriate alcohol, produced as a consequence of the alkylation of water. Increasing the leaving-group ability of the sulfonyl moiety on N-1 shortens the half-life, while the converse happens with N-2 substitutions. Linear Hammett relationships are found for both types of substitutions. The predictable kinetics of decomposition makes these agents potential candidates for use in regional chemotherapy, where compounds with tunable short half-lives may offer some advantage. Prodrugs of extremely short-lived derivatives of this class may also have utility as targeted alkylating agents.
Penketh
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PG
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520.
Shyam
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K
Sartorelli
A C
AC
D000477:Alkylating Agents / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry*; D004355:Drug Stability; D006834:Hydrazines / Q000737:chemistry*; D007700:Kinetics; D008763:Methylhydrazines / Q000737:chemistry; D008956:Models, Chemical; D013450:Sulfones / Q000737:chemistry; D014867:Water
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D006834:Hydrazines; D008763:Methylhydrazines; D013450:Sulfones; D014867:Water