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US 6,673,543 B2Granted
Solid phase synthesis of LXR ligands
AssigneesTularik Inc., Sumitomo Pharmaceuticals Company, Limited
InventorsJulio Medina, Naonori Imazaki
Life of this patent
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Abstract
The invention provides solid support synthetic methods for producing combinatorial libraries of modulators of LXRs. The combinatorial libraries thus produced are useful both as diagnostic indicators of LXRα function and as pharmacologically active agents. The combinatorial libraries find particular use in the treatment of disease states associated with cholesterol metabolism, particularly atherosclerosis and hypercholesterolemia.
Claims7
A method for preparing LXR ligands on a solid support, said method comprising:
- (a) attaching an aniline derivative to said solid support to provide a covalently attached support-bound aniline derivative, wherein said aniline derivative is of the formula:
- wherein PG is a protecting group;
- (b) removing said protecting group;
- (c) contacting said support-bound aniline derivative with an aldehyde or ketone, wherein the aldehdye is selected from the group consisting of optionally substituted (C1-C8)alkyl aldehyde, and an optionally substituted aryl aldehyde and a ketone selected from the group consisting of an optionally substituted dialkylketone, and a compound having the formula R3—C(O)—R4, wherein R3 and R4 are members each independently selected from the group consisting of optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl and optionally substituted alkyl, under reductively aminating conditions to provide a support-bound substituted aniline derivative;
- and
- (d) contacting said support-bound substituted aniline derivative with an acylating agent, wherein the acylating agent has the formula:
- R1—Y
- wherein
- R1 is a member selected from the group consisting of an optionally substituted (C8-C18)bicycloalkyl, an optionally substituted (C8-C18)tricycloalkyl, an optionally substituted (C8-C18)heterobicycloalkyl and an optionally substituted (C8-C18)heterotricycloalkyl;
- and
- Y is a member selected from the group consisting of a carboxylic acid, a carboxylate ester, a carboxylic acid chloride and other activated forms of carboxylic acids;
- to provide an LXR ligand on said solid support.
9 more elements
Dependencies are inferred from the claim text.