Conformationally restricted polyamine analogs as disease therapies
AssigneeCellgate, Inc.
InventorsBenjamin Frydman, Laurence J. Marton, Venodhar K. Reddy, Aldonia L. Valasinas, Andrei V. Blokhin, Hirak S. Basu
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Abstract
Novel conformationally restricted polyamine analogs are provided, as well as compositions comprising these novel polyamine analogs. Methods of using the novel polyamine analogs in treatment of diseases such as cancer are also provided. Also provided is a method of delivering these analogs specifically to tumor cells by covalently attaching polyamine analogs to porphyrin compounds, along with novel polyamine-porphyrin covalent conjugates.
Claims20
A composition comprising a porphyrin-polyamine conjugate or porphyrin-polyamine analog conjugate, wherein the conjugate comprises a polyamine compound or polyamine analog compound covalently linked to a porphyrin compound, and a pharmaceutically acceptable carrier, wherein the composition comprises a therapeutic amount of the porphyrin-polyamine conjugate or porphyrin-polyamine analog conjugate for treatment of cancer or uncontrolled cell proliferation, and with the proviso that the polyamine or polyamine analog is not spermine, and the proviso that the polyamine or polyamine analog does not have a tertiary amino group.
A porphyrin-polyamine conjugate or porphyrin-polyamine analog conjugate of the formula
- wherein at least one of J1–J8 is independently selected from the group consisting of -K1-G-L-(N(P)-A)n-K2
- where K1 is independently selected from the group consisting of C1–C8 alkyl and where the valence to the left of K1 attaches to the porphyrin ring;
- G is —O—, —(C═O)—, —C(═O)—O—, —O—(C═O)—, —O—(C═O)—O—, —O—(C═O)—N—, —N—(C═O)—O—, or a nonentity;
- L is C1–C8 alkyl, C3–C8 cycloalkyl, C3–C8 cycloaryl, C1–C8 alkoxy, C1–C8 alkyl-C3–C8 cycloalkyl, C1–C8 alkyl-C3–C8 cycloaryl, C1–C8 alkoxy-C3–C8 cycloaryl, C3–C8 cycloalkyl-C3–C8 cycloaryl, C3–C8 cycloalkyl-C1–C8 alkyl, C3–C8 cycloaryl-C1–C8 alkyl, C3–C8 cycloaryl-C1–C8 alkoxy, C3–C8 cycloaryl-C3–C8 cycloalkyl, or a nonentity;
- each A is independently selected from the group consisting of C1–C8 alkyl, C2–C8 alkenyl, C2–C8 alkynyl, C3–C8 cycloalkyl, C3–C8 cycloaryl, C3–C8 cycloalkenyl, and C3–C8 cycloalkynyl;
- P is independently selected from the group consisting of H and C1–C8 alkyl;
- n is an integer from 2 to 8;
- and K2 is independently selected from the group consisting of H, C1–C8 alkyl, C2–C8 alkenyl, C2–C8 alkynyl, C3–C8 cycloalkyl, C3–C8 cycloaryl, C3–C8 cycloalkenyl, C3C8 cycloalkynyl, C1–C8 alkanol, C3–C8 cycloalkanol, and C3–C8 hydroxyaryl;
- where the remainder of the groups J1–J8 are each independently selected from the group consisting of H, K3, or K4-COOH, where K3 is independently selected from the group consisting of C1–C8 alkyl, C2–C8 alkenyl, C2–C8 alkynyl, C3–C8 cycloalkyl, C3–C8 cycloaryl, C3–C8 cycloalkenyl, C3–C8 cycloalkynyl, C1–C8 alkanol, C3–C8 cycloalkanol, and C3–C8 hydroxyaryl;
- and K4 is independently selected from the group consisting of C1–C8 alkyl, C2–C8 alkenyl, C2–C8 alkynyl, C3–C8 cycloalkyl, C3–C8 cycloaryl, C3–C8 cycloalkenyl, and C3–C8 cycloalkynyl;
- or any salt or stereoisomer thereof.
A composition comprising a porphyrin-polyamine analog conjugate, wherein the conjugate comprises a polyamine analog compound covalently linked to a porphyrin compound, and a pharmaceutically acceptable carrier, wherein the composition comprises a therapeutic amount of the porphyrin-polyamine analog conjugate for treatment of cancer or uncontrolled cell proliferation, and with the proviso that the polyamine analog is conformationally restricted.
Dependencies are inferred from the claim text.