Use or cyclolignans and new cyclolignans
OwnerOlle Larsson, Magnus Axelsoninventors
Life of this patent
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Abstract
The invention refers to new compounds and the use thereof as well as the use of known cyclolignans having a trans configuration of the lactone ring as inhibitors of the insulin-like growth factor-1 receptor. Said compounds can be used for treatment of IGF-1R dependent diseases, especially cancer. Especially deoxypodophyllotoxin can be used for treatment of leukemia in humans.
Claims17
Use of a compound having the formula I
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- wherein the distance between the carbon atom of the methylene group and the carbon atom of the methoxy group is 0.85-1.05 nm;
- R is OH, OCH3, OC2H5 or a C1-5 linear or branched hydrocarbon chain with optionally a double bond, optionally having 1-3 oxygen functions, and optionally forming a bond with a carbon atom in the benzene ring A;
- R1, which can be the same or different, is OH or OCH3, and n is 0-2;
- for the preparation of a medicament inhibiting tyrosine phosphorylation of the insulin-like growth factor-1 receptor, but not of the insulin receptor:
Use of a compound having the formula I
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- wherein the distance between the carbon atom of the methylene group and the carbon atom of the methoxy group is 0.85-1.05 nm;
- R is OH, OCH3, OC2H5 or a C1-5 linear or branched hydrocarbon chain with optionally a double bond, optionally having 1-3 oxygen functions, and optionally forming a bond with a carbon atom in the benzene ring A;
- R1, which can be the same or different, is OH or OCH3, and n is 0-2;
- which compound inhibits the insulin-like growth factor-1 receptor (IGF-1R), but not the insulin receptor, for the preparation of a medicament for prophylaxis or treatment of IGF-1R dependent diseases.
A compound of the formula I
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- wherein R is OH, OCH3, OC2H5, CH3, C2H5, or C2H4OH;
- and R1, which can be the same or different, is OH or OCH3, and n is 0-2 for use as a medicament.
A compound of the formula II
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- wherein R2, R3 and R4, which can be the same or different, are H, OH, O, OCH3, or R2 and R3 together is a methylenedioxy group, or R3 and R4 together is an acetonide, carbonate or methylendioxy group;
- and R1, which can be the same or different, is OH or OCH3, and n is 0-2.
Method of treatment of a cancer in a mammal, comprising the steps of administrating a pharmaceutical composition, containing a compound having the formula I, II or III in combination with a physiologically acceptable carrier, by constant infusion to a patient suffering from a tumor, monitoring the plasma level of the compound, and adjusting the rate of infusion to keep the plasma level at a concentration of 0.05-5.0 μ, for a period of time being sufficient for the tumor to be retarded or to disappear.
Dependencies are inferred from the claim text.