DNA-binding polyamide drug conjugates

US7605125B2 · kind B2 · utility

Assignee

• The United States of America, as represented by the Department of Health and Human Services · US

Inventors

• Zoltan Szekely · Frederick, US
• Humcha K. Hariprakasha · Rockville, US
• Marek Cholody · Frederick, US
• Christopher J. Michejda · North Potomac, US

Key dates

• Filing date: Feb 27, 2003
• Grant date: Oct 20, 2009
• Expiry date: Oct 8, 2024

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K47/645
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A conjugate of formula: V—(Y)a—Z-T: (I), T-X—B—(Y)a—Z-T′: (II), V—(Y)a Z—(Y′)a V′: (III), T-X—B—(Y)a—Z—(Y′)a—X′—B′-T′: (IV), V—(Y)a—Z—(Y′)a—X—B-T: (V), V—(Y)a—Z—X—B—Z′—(Y′)a—(V′)b: (VI), or (W)a—(Y)b—[(Z)c—(Y′)d—(X—B)e—(Y″)f—(Z′)g]h—(Y . . . )i—(W′)j: (VII), in which W and W′ are independently a DNA intercalator or terminal subunit, V and V′ are independently a DNA intercalator, X and X′ are independently a DNA alkylator, B and B′ are the same or different and each is a heteoaromatic residue that is attached to the Nterminus of an alkylator subunit (X or X′), Y, Y′, Y″ and Y′″ are independently a linker, T and T′ are independently terminal subunits, Z and Z′ are independently a polyamide group that binds to the minor groove of DNA, a, b, c, d, f, g, i, and j are independently 0 to 5, and e and h are independently 1 to 5, a composition comprising a conjugate of any of formulae (I)-(VII) and a carrier, and a method for treating cancer in a mammal comprising administering an effective amount of a conjugate of any of formulae (I)-(VII) or a composition comprising same.