2-oxochromene derivatives
To provide a novel LXRβ agonist that is useful as a preventative and/or therapeutic agent for atherosclerosis; arteriosclerosis such as those resulting from diabetes; dyslipidemia; hypercholesterolemia; lipid-related diseases; inflammatory diseases that are caused by inflammatory cytokines; skin diseases such as allergic skin diseases; diabetes; or Alzheimer's disease. [Solving Means] A 2-oxochromene derivative represented by the following general formula (1) or salt thereof, or their solvate.
1. A 2-oxochromene derivative represented by the following general formula (1) or salt thereof:
(wherein R 1 represents a halo C 1-8 alkyl group; R 2 , R 3 , and R 4 are either same or different and represent a hydrogen atom, halogen atom, C 1-8 alkyl group, halo C 1-8 alkyl group, C 2-8 alkenyl group, C 2-8 alkynyl group, C 1-8 alkoxy group C 1-8 acyl group, nitro group, cyano group, carboxyl group, carbamoyl group, or C 6-10 aryl C 1-8 alkyl group, wherein the C 6-10 aryl may have 1 to 3 substituents selected from the following group A; R 5 and R 6 are either same or different and represent a hydrogen atom, C 1-8 alkyl group, C 3-8 cycloalkyl group, halo C 1-8 alkyl group, C 6-10 aryl group or 5- to 11-membered heterocyclic group, wherein the C 6-10 aryl group and 5- to 11-membered heterocyclic group may have 1 to 3 substituents selected from the following group A, and R 5 and R 6 may together form a C 3-8 cycloalkyl ring; L represents a C 2-10 alkyl chain, C 2-10 alkenyl chain, or C 2-6 alkyl-O—C 2-6 alkyl chain; X represents —O— or —N(R 7 )—; R 7 represents a hydrogen atom or C 1-8 alkyl group; Y represents an O, S, —CH(R 8 )—, —CH 2 CH(R 9 )—, —CH 2 O—, or) —N(R 10 )—; R 8 and R 9 are either same or different and represent a hydrogen atom or C 1-8 alkyl group; R 10 represents a hydrogen atom, C 1-8 alkyl group that may be substituted with a C 1-8 alkoxycarbonyl group, halo C 1-8 alkyl group, C 6-10 aryl group, or 5- to 11-membered heterocyclic group, wherein the C 6-10 aryl group and 5- to 11-membered heterocyclic group may have 1 to 3 substituents selected from the following group A), [Group A: halogen atom, C 1-8 alkyl group, halo C 1-8 alkyl group, C 2-8 alkenyl group, C 2-8 alkynyl group, C 3-8 cycloalkyl group, C 1-8 alkoxy group, halo C 1-8 alkoxy group, C 1-8 acyl group, nitro group, amino group, mono C 1-6 alkylamino group, di C 1-6 alkylamino group, cyano group, hydroxy group, carboxyl group, C 1-8 alkoxycarbonyl group, carbamoyl group, C 6-10 aryl group, 5- to 11-membered heterocyclic group, C 1-6 alkylthio group, C 1-6 alkylsulfonyl group, C 6-10 arylthio group, C 6-10 arylsulfonyl group, tetrahydropyranyloxy group, and C 1-6 alkylenedioxy group].
2. A medicine composition comprising a therapeutically effective amount of the 2-oxochromene derivative or salt thereof according to claim 1 as an active ingredient.
3. The medicine composition according to claim 2 , which is a therapeutic agent for atherosclerosis, arteriosclerosis resulting from diabetes, dyslipidemia, hypercholesterolemia, diabetes, or Alzheimer's disease.
4. An LXR regulator containing the 2-oxochromene derivative or salt thereof according to claim 1 as an active ingredient.
5. A pharmaceutical composition comprising the 2-oxochromene derivative or salt thereof according to claim 1 and a pharmaceutically acceptable carrier.
6. A method for treating atherosclerosis, arteriosclerosis resulting from diabetes, dyslipidemia, hypercholesterolemia, diabetes, or Alzheimer's disease, in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of the 2-oxochromene derivative or salt thereof according to claim 1 .
7. The medicine composition according to claim 2 wherein the medicine composition is administered in the form of an oral preparation, injection, suppository, ointment, inhalation, eye-drops, nasal preparation, or adhesive patch.
8. The LXR regulator according to claim 4 , wherein said LXR regulator has a higher selectivity for activating LXRβ expression than a LXRα expression.