Use of jasmonate ester derivatives for treating benign hyperproliferative skin disorders

摘要

The present invention relates to methods of treating benign hyperproliferative diseases of the epidermis by administering a composition comprising at least one jasmonate ester derivative. In particular, the present invention provides jasmonate ester derivatives as potent compounds useful for the treatment of disorders such as actinic keratoses with reduced side effects.

主权项

1. A method of treating a benign hyperproliferative skin disorder in a subject in need thereof, comprising the step of decreasing proliferation of abnormal hyperproliferative benign epidermal cells in said subject by exposing said cells to a proliferation decreasing-effective amount of a pharmaceutical composition comprising at least one jasmonate ester of formula III, so as to decrease proliferation of said hyperproliferative benign epidermal cells: wherein A is COR1; R1 is quinolinyloxy; R2 is selected from the group consisting of hydrogen, unsubstituted or substituted C1-C12 alkyl, unsubstituted or substituted C3-C8 cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, OR8, oxo and NR9aR9b; R3, R4, R5, R6 and R7 are each independently selected from the group consisting of hydrogen, halogen, unsubstituted or substituted C1-C12 alkyl, unsubstituted or substituted C1-C12 haloalkyl, unsubstituted or substituted C3-C8 cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, OR8 and NR9aR9b, or R5 and R6 together with the carbons to which they are attached form a C3-C8 cycloalkyl or a C3-C8 cycloalkyl substituted by halo; or one of R5 and R6 represents an oxygen atom which is bonded to C6, thereby forming an oxygen-containing 6 or 5 membered heterocyclic ring, respectively; wherein the bond between C9 and C10 can be a single or double bond; R8, R9a and R9b are each independently selected from the group consisting of hydrogen, unsubstituted or substituted C1-C12 alkyl, unsubstituted or substituted C3-C8 cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, glucosyl, or R9a and R9b can together with the nitrogen to which they are attached form an unsubstituted or substituted heterocyclic or heteroaromatic ring optionally containing one or more additional heteroatom selected from O, N and S; and n is selected from 0, 1 and 2; including salts, hydrates, solvates, polymorphs, optical isomers, geometrical isomers, enantiomers, diastereomers, and mixtures thereof.