Cytotoxic metal chelators and methods for making and using same

US6589966B1 · kind B1 · utility

Assignees

• Wake Forest University Health Sciences · US
• University of New Hempshire · US
• National Institutes of Health, Office of Technology Transfer · US

Inventors

• Suzy V. Torti · Winston-Salem, US
• Frank Torti · Palo Alto, US
• Roy P. Planalp · Portsmouth, US
• Martin W. Brechbiel · Annandale, US

Key dates

• Filing date: Sep 18, 2000
• Grant date: Jul 8, 2003
• Expiry date: Sep 18, 2020

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07C2601/14
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A family of hexadentate Fe(II) chelators having marked antiproliferative activity against tumor cells is disclosed. The cytotoxic metal chelators and complexes of the present invention are represented by the general formula below: wherein:X1, X3, and X5 are N, O or S, wherein the X1, X3, and X5 atoms are at the 1, 3, and 5 positions of a cyclohexyl group and are in a cis, cis disposition;B, B′, and B″ are aliphatic, branched aliphatic, or aryl groups, or any combination thereof, wherein the number of atoms between X and Y is about 2 to about 4;Y, Y′ and Y″ contain N, O, or S atoms that originate from either aliphatic, branched aliphatic, aryl, or heterocyclic groups, or any combination thereof, and/or Y, Y′ and Y″ are NH2 or NHR, OH, or SH, CO2H, P(O)(OH)2, RP(O)OH, ROP(O)OH groups or a combination thereof, and R is H, aliphatic, branched aliphatic, or aryl groups, or any combination thereof that may or may not be identical in Y, Y′ and Y″;s, s′, and s″ are 0 to about 2; andt, t′, and t″ are 0 to about 2. Application of the metal chelators of the present invention as chemotherapeutic agents is also disclosed.