WO2005023247A1

WO2005023247A1 - Compounds and methods

Info

Publication number: WO2005023247A1
Application number: PCT/US2004/028629
Authority: WO
Inventors: Tram H. Hoang; Scott K. Thompson; David G. Washburn
Original assignee: Smithkline Beecham Corporation
Priority date: 2003-09-03
Filing date: 2004-09-02
Publication date: 2005-03-17

Abstract

Disclosed are compounds and pharmaceutically acceptable salts thereof, useful as LXR agonists.

Description

COMPOUNDS AND METHODS

FIELD OF THE INVENTION The present invention relates to compounds useful as modulating agents for liver X receptors (LXR). Additionally, the present invention relates to pharmaceutical formulations comprising such compounds, and the therapeutic use of the same.

BACKGROUND OF THE INVENTION LXR is a transcription factor. The orphan nuclear receptors, LXRα and LXRβ (collectively LXR) play a role in the maintenance of cholesterol balance. Peet et. al., Curr. Opin. Genet. Dev. 8:571-575 (1998). In addition, LXR binds to the ATP Binding Cassette Transporter-1 (ABCA1) gene and increases expression of the gene to result in increased ABCA1 protein. ABCA1 is a membrane bound transport protein that is involved in the regulation of cholesterol efflux from extrahepatic cells onto nascent HDL particles. Mutations in the ABCA1 gene are responsible for genetic diseases that result in the complete absence or low levels of HDL cholesterol and a concomitant highly increased risk of cardiovascular disease. See Brooks-Wilson et al., Nat. Genet. 22:336-345 (1999); Bodzioch er al., Nat. Genet. 22: 347-351 (1999); and Rust et al., Nat. Genet. 22:352-355 (1999). ABCA1 knockout mice homozygous for the mutation in the ABCA1 gene have virtually no plasma HDL, whereas the heterozygotes produce 50% of the HDL of wild type animals. See, Orso et al., Nat. Genet. 24:192-196 (2000) and McNeish et al., Proc. Natl. Acad. Sci. USA 97:4245-4250 (2000). ABCA1 knockout mice also show increased cholesterol absorption. See, McNeish er a/., Proc. Natl. Acad. Sci. USA 97:4245-4250 (2000). Increased expression of ABCA1 results in increased HDL cholesterol, decreased absorption of cholesterol, and increased removal of excess cholesterol from extrahepatic tissues, including macrophages. LXR agonists also upregulate macrophage expression of apolipoprotein E and ABCG1 , both of which contribute to the efflux of cellular cholesterol. By stimulating macrophage cholesterol efflux through upregulation of ABCA1 , ABCG1 , and apoE expression, as well as increasing the expression of other target genes including cholesteryl ester transfer protein and Hpoprotein lipase, LXR agonists influence plasma lipoproteins. Accordingly, compounds which function as LXR modulating agents, and particularly as LXR agonists, would be useful in methods of increasing ABCA1 , ABCG1 , and apolipoprotein E expression, increasing cholesterol efflux from peripheral cells, and treating LXR mediated diseases and conditions such as cardiovascular disease and inflammation. SUMMARY OF THE INVENTION This invention is directed to a compound of Formula I:

wherein: the A ring is an accessible 5-membered aromatic heterocyclic group comprising 1 , 2 or 3 heteroatoms each independently selected from N, O or S, wherein the N or S heteroatom is optionally oxidized (forming an NO, SO, or SO₂ ring moiety); Y is selected from -O-, -S-, -N(R⁸)-, and -C(R )(R³)-; W¹ is selected from C₃-C₈ cycloalkyl, aryl and Het, wherein said C₃-C₈ cycloalkyl, aryl and Het are optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, C C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, -Co-C₆ alkyl-CO₂R⁸, -C₀-C₆ alkyl-C(O)SR⁸, -C₀-C₆ alkyl-CONR⁹R¹⁰, -C₀-C₆ alkyl-COR¹¹, -Co-C₆ alkyl-NR⁹R¹⁰, -C₀-C₆ alkyl-SR⁸, -C₀-C₆ alkyl-OR⁸, -C₀-C₆ alkyl-SO₃H, -Co-C₆ alkyl-SO₂NR⁹R¹⁰, -C₀-C₆ alkyl-SO₂R¹⁴, -C₀-C₆ alkyl-SOR¹¹, -C₀-C₆ alkyl-OCOR¹¹, -Co-C₆ alkyl-OC(O)NR⁹R¹⁰, -C₀-C₆ alkyl-OC(O)OR¹¹, -C₀-C₆ alkyl-NR ⁵C(O)OR¹¹, -Co-C₆ alkyl-NR¹⁵C(O)NR⁹R¹⁰, and -C₀-C₆ alkyl-NR¹⁵COR¹¹, where said Cι-C₆ alkyl, is optionally unsubstituted or substituted by one or more halo substituents; W² is selected from H, halo, Ci-Ce alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, -C₀-C₆ alkyl-NR⁹R¹⁰, -C₀-C₆ alkyl-SR⁸, -C₀-C₆ alkyl-OR⁸, -C₀-C₆ alkyl-CO₂R⁸,

-C₀-C₆ alkyl-C(O)SR⁸, -C₀-C₆ alkyl-CONR⁹R¹⁰, -C₀-C₆ alkyl-COR¹¹, -C₀-C₆ alkyl-OCOR¹¹, -Co-C₆ alkyl-OCONR⁹R¹⁰, -C₀-C₆ alkyl-NR¹⁵CONR⁹R¹⁰, -C₀-C₆ alkyl-NR¹⁵COR¹¹, -C₀-C₆ alkyl-Het, -C₀-C₆ alkyl-Ar and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl, wherein said Cι-C₆ alkyl is optionally unsubstituted or substituted by one or more halo substituents, and wherein the C₃-C₇ cycloalkyl, Ar and Het moieties of said -C₀-C₆ alkyl-Het, -C₀-C₆ alkyl-Ar and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl are optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, C^Ce alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, -C₀-C₆ alkyl-CO₂R⁸, -C₀-C₆ alkyl-C(O)SR⁸, -C₀-C₆ alkyl-CONR⁹R¹⁰, -Co-Ce alkyl-COR¹¹, -C₀-C₆ alkyl-NR⁹R¹⁰, -C₀-C₆ alkyl-SR⁸, -C₀-C₆ alkyl-OR⁸, -Co-Ce alkyl-SO₃H, -C₀-C₆ alkyl-SO₂NR⁹R¹⁰, -C₀-C₆ alkyl-SO₂R¹⁴, -C₀-C₆ alkyl-SOR¹¹, -Co-Ce alkyl-OCOR¹¹, -C₀-C₆ alkyl-OC(O)NR⁹R¹⁰, -C₀-C₆ alkyl-OC(O)OR¹¹, -Co-Ce alkyl-NR¹⁵C(O)OR¹¹, -C₀-C₆ alkyl-NR¹⁵C(O)NR⁹R¹⁰, and -C₀-C₆ alkyl-NR¹⁵COR¹¹, where said C C₆ alkyl, is optionally unsubstituted or substituted by one or more halo substituents; W³ is selected from H, halo, C C₆ alkyl, -C₀-C₆ alkyl-NR⁹R¹⁰, -C₀-C₆ alkyl-SR⁸, -Co-C₆ alkyl-OR⁸, -C₀-C₆ alkyl-CO₂R⁸, -C₀-C₆ alkyl-C(O)SR⁸, -C₀-C₆ alkyl-CONR⁹R¹⁰, -Co-Ce alkyl-COR¹¹, -C₀-C₆ alkyl-OCOR¹¹, -C₀-C₆ alkyl-OCONR⁹R¹⁰, -Co-Ce alkyl-NR¹⁵CONR⁹R¹⁰, -C₀-C₆ alkyl-NR¹⁵COR¹¹, -C₀-C₆ alkyl-Het, -d-Cg alkyl-Ar and -C Ce alkyl-C₃-C₇ cycloalkyl, wherein said C C₆ alkyl is optionally unsubstituted or substituted by one or more halo substituents; Q is selected from C₃-C₈ cycloalkyl, Ar and Het; wherein said C₃-C₈ cycloalkyl, Ar and Het are optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, C C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl,

-Co-Ce alkyl-CO₂R⁸, -C₀-C₆ alkyl-C(O)SR⁸, -C₀-C₆ alkyl-CONR⁹R¹⁰, -C₀-C₆ alkyl-COR¹¹, -Co-Ce alkyl-NR⁹R¹⁰, -C₀-C_e alkyl-SR⁸, -C₀-C₆ alkyl-OR⁸, -C₀-C₆ alkyl-SO₃H, -Co-Ce alkyl-SO₂NR⁹R¹⁰, -C₀-C₆ alkyl-SO₂R¹⁴, -C₀-C₆ alkyl-SOR¹¹, -C₀-C₆ alkyl-OCOR¹¹, -Co-C₆ alkyl-OC(O)NR⁹R¹⁰, -C₀-C₆ alkyl-OC(O)OR¹¹, -C₀-C₆ alkyl-NR¹⁵C(O)OR¹¹, -Co-Ce alkyl-NR¹⁵C(O)NR⁹R¹⁰, and -C₀-C₆ alkyl-NR¹⁵COR¹¹, where said d-Ce alkyl is optionally unsubstituted or substituted by one or more halo substituents; k is O, 1 or 2; n is 2-8; m is 0 or 1 ; q is 0 or 1 ; t is 0 or 1 ; each R¹ is the same or different and is independently selected from halo, cyano, nitro, oxo, C C₁₂ alkyl, -C₂-C₁₂ alkenyl, -C₂-C₄ alkyl -OR⁸, -C₂-C₄ alkyl-NR¹²R¹³, -C C₄ alkyl-CN, -C₀-C₄ alkyl-COOR⁸, -C₀-C₄ alkyl-COR¹¹, -C₂-C₄ alkyl-OCOR¹¹, -C₀-C₄ alkyl-CONR¹²R¹³, -C₂-C₄ alkyl-N(R¹⁵)COR¹¹, -C₀-C₄ alkyl-SO₃H, -Co-C₄ alkyl-SO₂R¹⁴, -C₀-C₄ alkyl-SO₂NR⁹R¹⁰, -C₀-C₄-C(=NR¹⁵)NR⁹R¹⁰, -C₂-C₄ alkyl-N(R¹⁵)SO₂R¹⁴, and -C C₄ alkyl-Het, where Het is a 5 or 6-membered heterocyclic group; each R² and R³ is independently selected from H, halo, C C₆ alkyl, -Co-Ce alkyl-Het, -C₀-C₆ alkyl-Ar and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl; R⁴ and R⁵ are each independently selected from H, halo, Cι-C₆ alkyl, -Co-Ce alkyl-Het, -C₀-C₆ alkyl-Ar and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl; R⁶ and R⁷ are each independently selected from H, halo, Cι-C₆ alkyl, -Co-C₆ alkyl-Het, -C₀-C₆ alkyl-Ar and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl; R⁸ is selected from H, d-C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, -C₀-C₆ alkyl-Ar,

-Co-C₆ alkyl-Het and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl; each R⁹ and each R¹⁰ are independently selected from H, C Ce alkyl, C₃-C₈ alkenyl, C₃-C₆ alkynyl, -C₀-C₆ alkyl-Ar, -C₀-C₆ alkyl-Het and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl, or R⁹ and R¹⁰ together with the nitrogen to which they are attached form a 4-7 membered heterocyclic ring which optionally contains one or more additional heteroatoms selected from N, O, and S; R¹¹ is selected from d-C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, -C₀-C₆ alkyl-Ar, -Co-C₆ alkyl-Het and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl; R¹² and R¹³ are each independently selected from H, d-C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, -C₀-C₆ alkyl-Ar, -C₀-C₆ alkyl-Het, -C₀-C₆ alkyl-C₃-C₇ cycloalkyl, -Co-Ce alkyl-O-Ar, -C₀-C₆ alkyl-O-Het, -C₀-C₆ alkyl-O-C₃-C₇ cycloalkyl, -Co-C₆ alkyl-S(O)_x-Cι-C₆ alkyl, -C₀-C₆ alkyl-S(O)_x-Ar, -C₀-C₆ alkyl-S(O)_x-Het, -Co-Ce alkyl-S(O)_x-C₃-C₇ cycloalkyl, -C₀-C₆ alkyl-NH-Ar, -C₀-C₆ alkyl-NH-Het, -Co-Ce alkyl-NH-C₃-C₇ cycloalkyl, -C₀-C₆ alkyl-N(Cι-C₄ alkyl)-Ar, -Co-C₆ alkyl-N(C C₄ alkyl)-Het, -C₀-C₆ alkyl-N(Cι-C₄ alkyl)-C₃-C₇ cycloalkyl,

-Co-Ce alkyl-Ar, -C₀-C₆ alkyl-Het and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl, where x is 0, 1 or 2, or R¹² and R¹³, together with the nitrogen to which they are attached, form a 4-7 membered heterocyclic ring which optionally contains one or more additional heteroatoms selected from N, O, and S, wherein said d-C₆ alkyl is optionally substituted by one or more of the substituents independently selected from halo, -OH, -SH, -NH₂, -NH(unsubstituted C C₆ alkyl), -N(unsubstituted Ci-Ce alkyl)(unsubstituted d-C₆ alkyl), unsubstituted -OCι-C₆ alkyl, -CO₂H, -CO₂(unsubstituted d-C₆ alkyl), -CONH₂, -CONH(unsubstituted Ci-C₆ alkyl), -CON(unsubstituted d-C₆ alkyl)(unsubstituted d-C₆ alkyl), -SO₃H, -SO₂NH₂, -SO₂NH(unsubstituted d-C₆ alkyl) and -SO₂N(unsubstituted d-C₆ alkyl)(unsubstituted Cι-C₆ alkyl); R¹⁴ is d-C₆ alkyl, -C₀-C₆ alkyl-C₃-C₇ cycloalkyl, -C₀-C₆ alkyl-Ar or -C₀-C₆ alkyl-Het; and R¹⁵ is H, d-C-e alkyl, -C₀-C₆ alkyl-C₃-C₇ cycloalkyl, -C₀-C₆ alkyl-Ar or -Co-Ce alkyl-Het; or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof. Unless otherwise provided, each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, aryl or Het (including any 3-5-membered, 4-7-membered, 5-6-membered or 5-7-membered carbocyclic or heterocyclic rings or ring moieties) herein is independently unsubstituted or substituted with one ore more substituents defined hereinbelow. Also included within the scope of this invention are methods for preparing compounds of this invention, or pharmaceutically acceptable salts or solvates thereof and methods of using the same. The present invention also provides pharmaceutical compositions comprising a compound of this invention, or a pharmaceutically acceptable salt or solvate thereof. LXR mediated diseases or conditions include inflammation, cardiovascular disease and atherosclerosis. Accordingly, the methods of this invention further comprise methods for increasing reverse cholesterol transport, inhibiting cholesterol absorption, and decreasing inflammation. The present invention also provides pharmaceutical compositions comprising a compound of this invention.

DETAILED DESCRIPTION OF THE INVENTION As used herein, the term "alkyl" represents a straight-or branched-chain saturated hydrocarbon, containing 1 to 10 carbon atoms, unless otherwise provided, which may be unsubstituted or substituted by one or more of the substituents described below. Exemplary alkyls include, but are not limited to methyl (Me), ethyl (Et), n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, neopentyl and hexyl and structural isomers thereof. Any "alkyl" herein may be optionally substituted by one or more of the substituents independently selected from halo, -OH, -SH, -NH₂, -NH(unsubstituted Cι-C₆ alkyl), -N(unsubstituted d-Cβ alkyl)(unsubstituted Ci-Ce alkyl), unsubstituted -Od-C₆ alkyl, -CO₂H, and -CO₂(unsubstituted C C₆ alkyl). When combined with another substituent term (e.g., aryl or cycloalkyl as in -alkyl-Ar or -alkyl-cycloalkyl), the "alkyl" term therein refers to an alkylene moiety, that is, an unsubstituted divalent straight-or branched-chain saturated hydrocarbon moiety, containing 1 to 10 carbon atoms, unless otherwise provided. For example, the term "-C₀-C₈ alkyl-Ar", where C is 1-6 is intended to mean the radical -alkyl-aryl (e.g., -CH₂-aryl or -CH(CH₃)-aryl) and is represented by the bonding arrangement present in a benzyl group. The term "C₀ alkyl" in a moiety, such as -C₀-C₆ alkyl-Ar or -O-(C₀-C₆ alkyl)-Ar, provides for no alkyl/alkylene group being present in the moiety. Thus, when C is zero, -C₀-C₆ alkyl-Ar is equivalent to -Ar and -O-(C₀-C₆ alkyl)-Ar is equivalent to -O-Ar. As used herein, the term "alkenyl" represents a straight-or branched-chain hydrocarbon, containing 2 to 10 carbon atoms, unless otherwise provided, and one or more carbon-carbon double bonds. Alkenyl groups may be unsubstituted or substituted by one or more of the substituents described below. Exemplary alkenyls include, but are not limited ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, isobutenyl, butadienyl, pentenyl and hexenyl and structural isomers thereof. Both cis (Z) and trans (E) isomers of each double bond that may be present in the compounds of this invention are included within the scope of this invention. Any "alkenyl" herein may be optionally substituted by one or more of the substituents independently selected from halo, -OH, -SH, -NH₂, -NH(unsubstituted Ci-Ce alkyl), -N(unsubstituted C C₆ alkyl)(unsubstituted C -Ce alkyl), unsubstituted -OC C₆ alkyl, -CO₂H, and -CO₂(unsubstituted Ci-Ce alkyl). As used herein, the term "alkynyl" represents a straight-or branched-chain hydrocarbon, containing 2 to 10 carbon atoms, unless otherwise provided, and one or more carbon-carbon triple bonds and, optionally, one or more carbon-carbon double bonds. Both cis (Z) and trans (E) isomers of each double bond that may be present in the compounds of this invention are included within the scope of this invention. Exemplary alkynyls include, but are not limited ethynyl, propynyl (propargyl, isopropynyl), 1-butynyl, 2-butynyl, 3-butynyl, pentynyl and hexynyl and structural isomers thereof. Any "alkynyl" herein may be optionally substituted by one or more of the substituents independently selected from halo, -OH, -SH, -NH₂, -NH(unsubstituted C C₆ alkyl), -N(unsubstituted Cι-C₆ alkyl)(unsubstituted d-C₆ alkyl), unsubstituted -Od-C₆ alkyl, -CO₂H, and -CO₂(unsubstituted Ci-Ce alkyl). For the purposes of this invention, when an alkenyl or alkynyl group is a substituent on an oxygen, nitrogen or sulfur atom (e.g., as in oxy (-OR), thio (-SR), ester (-CO₂R or -C(O)SR), amino (-NRR) or amido (-CONRR) moieties and the like), it is understood that a double or triple bond of the alkenyl or alkynyl group is not located on carbons that are α,β to the oxygen, nitrogen or sulfur atom. Compounds containing ene- amino or enol-type moieties (-NR-CR=CR- or -O-CR=CR-) are not intended to be included within the scope of this invention. "Cycloalkyl" represents a non-aromatic monocyclic, bicyclic, or tricyclic hydrocarbon containing from 3 to 10 carbon atoms which may be unsubstituted or substituted by one or more of the substituents described below and may be saturated or partially unsaturated. Exemplary cycloalkyls include monocyclic rings having from 3-7, preferably 3-6, carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclopentadienyl, cyclohexyl, cyclohexenyl and cycloheptyl. Any "cycloalkyl" herein may be optionally substituted by one or more of the substituents independently selected from halo, cyano, Cι-C₆ alkyl (which specifically includes d-C₈ haloalkyl, -C₀-C₆ alkyl-OH, -Co-Ce alkyl-SH and -C₀-C₆ alkyl-NR'R"), C₃-C₆ alkenyl, oxo, -Od-C₆alkyl, -OCi-C₆ alkenyl, -C₀-C₆ alkyl-COR', -C₀-C₆ alkyl-CO₂R', -C₀-C₆ alkyl-CONR'R", -OCo-Ce alkyl-CO₂H, -OC₂-C₆ alkyl-NR'R", and -C₀-C₆ alkyl-SO₂NR'R", wherein each R' and R" are independently selected from H and unsubstituted Ci-Ce alkyl. The terms "Ar" or "aryl" as used herein interchangeably at all occurrences mean a substituted or unsubstituted carbocyclic aromatic group, which may be optionally fused to another carbocyclic aromatic group moiety or to a cycloalkyl group moiety, which may be optionally substituted or unsubstituted. Examples of suitable Ar or aryl groups include phenyl, naphthyl indenyl, 1-oxo-1H-indenyl and tetrahydronaphthyl. Any "Ar", "aryl" or "phenyl" herein may be optionally unsubstituted or substituted by one or more of the substituents independently selected from halo, cyano, Cι-C₆ alkyl (which specifically includes d-C₆ haloalkyl, -C₀-C₆ alkyl-OH, -C₀-C₆ alkyl-SH and -C₀-C₆ alkyl-NR'R"), C₃-C₆ alkenyl, -Od-C₆alkyl, -Od-C₆ alkenyl, -C₀-C₆ alkyl-COR', -C₀-C₆ alkyl-CO₂R', -Co-Ce alkyl-CONR'R", -OC₀-C₆ alkyl-CO₂H, -OC₂-C₆ alkyl-NR'R", -Co-Ce alkyl-C(=NR')NR'R", and -C₀-C₆ alkyl-SO₂NR'R", wherein each R' and R" are independently selected from H and unsubstituted Ci-Ce alkyl. The term "Het" as used herein means a stable 5- to 7-membered monocyclic, a stable 7- to 10-membered bicyclic, or a stable 11- to 18-membered tricyclic heterocyclic ring group, any of which are saturated, unsaturated or aromatic, and consist of carbon atoms and from one to three heteroatoms selected from N, O and S, and which includes bicyclic and tricyclic rings containing one or more fused cycloalkyl, aryl (e.g., phenyl) or heteroaryl (aromatic Het) ring moieties. As used herein the term "Het" is also intended to encompass heterocyclic groups containing nitrogen and/or sulfur where the nitrogen or sulfur heteroatoms are optionally oxidized or the nitrogen heteroatom is optionally quatemized. The heterocyclic group may be attached at any heteroatom or carbon atom that results in the creation of a stable structure. Any "Het" herein may be optionally unsubstituted or substituted by one or more of the substituents independently selected from halo, cyano, d-C₆ alkyl (which specifically includes Ci-Ce haloalkyl, -C₀-C₆ alkyl-OH, -Co-Ce alkyl-SH and -C₀-C₆ alkyl-NR'R"), C₃-C₆ alkenyl, oxo, -Od-Cealkyl, -Od-Ce alkenyl, -C₀-C₆ alkyl-COR', -C₀-C₆ alkyl-CO₂R', -C₀-C₆ alkyl-CONR'R", -OCo-Ce alkyl-CO₂H, -OC₂-C₆ alkyl-NR'R", -C₀-C₆ alkyl-C(=NR')NR'R" and

-C₀-C₆ alkyl-SO₂NR'R", wherein each R' and R" are independently selected from H and unsubstituted d-C₆ alkyl. Examples of such heterocyclic groups include, but are not limited to piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, azepanyl, pyrrolyl, 4-piperidonyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, pyridinyl, pyrazinyl, oxazolidinyl, oxazolinyl, oxazolyl, isoxazolyl, morpholinyl, thiamorpholinyl (or thiomorpholinyl), thiazolidinyl, thiazolinyl, thiazolyl, 1 ,3-benzodioxolyl (e.g., methylenedioxy-substituted phenyl), 1 ,4-benzodioxolyl, quinuclidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, benzoxazolyl, furyl (or furanyl), pyranyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, benzoxazolyl, benzofuranyl, benzothienyl, dihydrobenzofuranyl, dihydrobenzothienyl, dihydroindolyl, tetrazolyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, and oxadiazolyl, as well as triazolyl, thiadiazolyl, oxadiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyridazinyl, pyrimidinyl and triazinyl which are available by routine chemical synthesis and are stable. Examples of the 4-7 membered heterocyclic rings useful in the compounds of this invention, include, but are not limited to azetidinyl, piperidinyl, piperazinyl, 2- oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, azepanyl, pyrrolyl, 4-piperidonyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, pyridinyl, pyrazinyl, oxazolidinyl, oxazolinyl, oxazolyl, isoxazolyl, morpholinyl, thiamorpholinyl (or thiomorpholinyl), thiazolidinyl, thiazolinyl, thiazolyl, furyl (or furanyl), pyranyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, tetrazolyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, and oxadiazolyl, as well as triazolyl, thiadiazolyl, oxadiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyridazinyl, pyrimidinyl and triazinyl which are available by routine chemical synthesis and are stable. The 4-7 membered heterocyclic group may be optionally unsubstituted or substituted by one or more of the substituents independently selected from halo, cyano, Cι-C₆ alkyl (which specifically includes C C₆ haloalkyl, -C₀-C₆ alkyl-OH, -Co-Ce alkyl-SH and -C₀-C₆ alkyl-NR'R"), C₃-C₆ alkenyl, oxo, -Od-C₆alkyl, -Od-Ce alkenyl, -C₀-C₆ alkyl-COR', -C₀-C₆ alkyl-CO₂R', -C₀-C₆ alkyl-CONR'R", -OCo-C₆ alkyl-CO₂H, -OC₂-C₆ alkyl-NR'R", -C₀-C₆ alkyl-C(=NR')NR'R" and -C₀-C₆ alkyl-SO₂NR'R", wherein each R' and R" are independently selected from H and unsubstituted Ci-Ce alkyl. Examples of 5 or 6 membered heterocyclic groups include, but are not limited to piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, pyrrolyl, 4- piperidonyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, pyridinyl, pyrazinyl, oxazolidinyl, oxazolinyl, oxazolyl, isoxazolyl, morpholinyl, thiamorpholinyl (or thiomorpholinyl), thiazolidinyl, thiazolinyl, thiazolyl, furyl (or furanyl), pyranyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, tetrazolyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, and oxadiazolyl, as well as triazolyl, thiadiazolyl, oxadiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyridazinyl, pyrimidinyl and triazinyl which are available by routine chemical synthesis and are stable. The 5-6 membered heterocyclic group may be attached at any heteroatom or carbon atom that results in the creation of a stable structure. The 5-6 membered heterocyclic group may be optionally unsubstituted or substituted by one or more of the substituents independently selected from halo, cyano, Cι-C₆ alkyl (which specifically includes Ci-Ce haloalkyl, -C₀-C₆ alkyl-OH, -C₀-C₆ alkyl-SH and -Co-Ce alkyl-NR'R"), C₃-C₆ alkenyl, oxo, -OCι-C₆alkyl, -OCι-C₆ alkenyl, -Co-Ce alkyl-COR', -C₀-C₆ alkyl-CO₂R', -C₀-C₆ alkyl-CONR'R", -OC₀-C₆ alkyl-CO₂H, -OC₂-Ce alkyl-NR'R", -C₀-C₆ alkyl-C(=NR')NR'R" and -C₀-C₆ alkyl-SO₂NR'R", wherein each R' and R" are independently selected from H and unsubstituted C C₆ alkyl. The terms "halogen" and "halo" represent chloro, fluoro, bromo or iodo substituents. "Alkoxy" is intended to mean the radical -OR_a, where R_a is an alkyl group, wherein alkyl is as defined above, provided that -O-d alkyl may be optionally substituted by one or more of the substituents independently selected from halo and -CO₂H.

Exemplary alkoxy groups include methoxy, ethoxy, propoxy, and the like. "Phenoxy" is intended to mean the radical -OR_ar, where R_ar is a phenyl group. "Acetoxy" is intended to mean the radical -O-C(=O)-methyl. "Benzoyloxy" is intended to mean the radical -O- C(=O)-phenyl. "Alkylenedioxy" is intended to mean the divalent radical -OR_aO- which is bonded to adjacent atoms (e.g., adjacent atoms on a phenyl or naphthyl ring), wherein R_a is a lower alkyl group. "Oxo" is intended to mean the keto diradical =O, such as present on a pyrrolidin-2-one ring. If a substituent described herein is not compatible with the synthetic methods of this invention, the substituent may be protected with a suitable protecting group that is stable to the reaction conditions used in these methods. The protecting group may be removed at a suitable point in the reaction sequence of the method to provide a desired intermediate or target compound. Suitable protecting groups and the methods for protecting and de-protecting different substituents using such suitable protecting groups are well known to those skilled in the art; examples of which may be found in T. Greene and P. Wuts, Protecting Groups in Chemical Synthesis (3rd ed.), John Wiley & Sons, NY (1999), which is incorporated herein by reference in its entirety. In some instances, a substituent may be specifically selected to be reactive under the reaction conditions used in the methods of this invention. Under these circumstances, the reaction conditions convert the selected substituent into another substituent that is either useful as an intermediate compound in the methods of this invention or is a desired substituent in a target compound. The term "pharmaceutically acceptable salt" is intended to describe a salt that retains the biological effectiveness of the free acid or base of a specified compound and is not biologically or otherwise undesirable. If an inventive compound is a base, a desired salt may be prepared by any suitable method known in the art, including treatment of the free base with an inorganic acid, such as hydrochloric acid, hydrobromic acid, sulfuhc acid, sulfamic acid, nitric acid, phosphoric acid, metaphosphoric acid and the like, or with an organic acid, such as acetic acid, trifluoroacetic acid, formic acid, maleic acid, lactic acid, succinic acid, mandelic acid, fumaric acid, malonic acid, malic acid, pyruvic acid, oxalic acid, glycolic acid, citric acid, tartaric acid, gluconic acid, glutaric acid, lactobionic, orotic, cholic, a pyranosidyl acid, such as glucuronic acid or galacturonic acid, an amino acid, such as aspartic acid or glutamic acid, an aromatic acid, such as benzoic acid, salicylic acid, cinnamic acid, pamoic acid or 1-hydroxy-2-naphthoic acid, a sulfonic acid, such as benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, methanesulfonic acid, ethanesulfonic acid or the like. Additional examples of pharmaceutically acceptable salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caproates, heptanoates, propiolates, oxalates, malonates succinates, suberates, sebacates, fumarates, maleates, butyne-1 ,4-dioates, hexyne-1 ,6-dioates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, phthalates, phenylacetates, phenylpropionates, phenylbutrates, citrates, lactates, γ-hydroxybutyrates, glycollates, tartrates mandelates, and sulfonates, such as xylenesulfonates, methanesulfonates, propanesulfonates, naphthalene-1- sulfonates and naphthalene-2-sulfonates. Embodiments of a pharmaceutically acceptable salts (e.g., hydrochloride salts, methanesulfonate salts, and trifluoroacetic acid salts, and the like) of the compounds of this invention are provided in the Examples. If an inventive compound is an acid, a desired salt may be prepared by any suitable method known to the art, including treatment of the free acid with an excess of an inorganic or organic alkaline reagent. Illustrative examples of suitable salts include salts derived from ammonia; primary, secondary, tertiary amines (including secondary and tertiary cyclic amines), such as ethylene diamine, dicyclohexylamine, ethanolamine, piperidine, morpholine, and piperazine; salts derived from amino acids such as glycine and arginine; as well as salts derived from an alkali metal , alkaline earth metal, or ammonium hydroxide, carbonate, alkoxide or sulfate, such as sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium sulfate, etc., and corresponding alkaline salts containing , for example, Li⁺, K⁺, Ca⁺⁺, Mg⁺⁺ and NH₄ ⁺ cations. The term "solvate" is intended to mean a pharmaceutically acceptable solvate form of a specified compound of this invention, or a salt thereof, that retains the biological effectiveness of such compound. Examples of solvates include compounds of the invention in combination with water, isopropanol, ethanol, methanol, DMSO, ethyl acetate, acetic acid, or ethanolamine. In the case of compounds, salts, or solvates that are solids, it is understood by those skilled in the art that the inventive compounds, salts, or solvates may exist in different crystal forms, all of which are intended to be within the scope of the present invention and specified formulas. Because the compounds of this invention may contain both acid and base moieties, pharmaceutically acceptable salts may be prepared by treating these compounds with an alkaline reagent or an acid reagent, respectively. Accordingly, this invention also provides for the conversion of one pharmaceutically acceptable salt of a compound of this invention, e.g., a hydrochloride salt, into another pharmaceutically acceptable salt of a compound of this invention, e.g., a mesylate salt or a sodium salt. Also included within the scope of this invention are prodrugs of the compounds of this invention. A prodrug of this invention can be converted under physiological conditions, e.g., by solvolysis or metabolically to a compound that is active as an LXR modulator and may be, itself, active as an LXR modulator. For example, a prodrug may be a derivative of one of the compounds of this invention that contains a carboxylic or phosphoric acid ester or amide moiety that may be cleaved under physiological conditions. A prodrug containing such a moiety may be prepared according to conventional procedures, for example, by treatment of a compound of this invention containing an amino, amido or hydroxyl moiety with a suitable derivatizing agent, for example, a carboxylic or phosphoric acid halide or acid anhydride, or by converting a carboxyl moiety of a compound of this invention to an ester or amide. Prodrugs of the compounds of this invention may be determined using techniques known in the art, for example, through metabolic studies. See, e.g., "Design of Prodrugs," (H. Bundgaard, Ed.) 1985, Elsevier Publishers B.V., Amsterdam, The Netherlands. It will be appreciated by those skilled in the art that the compounds of this invention may exist in different tautomeric forms. All tautomehc forms of the compounds described herein are intended to be encompassed within the scope of the present invention. The compounds of this invention may contain at least one chiral center and may exist as single stereoisomers (e.g., single enantiomers), mixtures of stereoisomers (e.g., any mixture of enantiomers or diastereomers) or racemic mixtures thereof. All such single stereoisomers, mixtures and racemates are intended to be encompassed within the broad scope of the present invention. Compounds identified herein as single stereoisomers are meant to describe compounds that are present in a form that are at least 90% enantiomerically pure. Where the stereochemistry of the chiral carbons present in the chemical structures illustrated herein is not specified, the chemical structure is intended to encompass compounds containing either stereoisomer of each chiral center present in the compound. Such compounds may be obtained synthetically, according to the procedures described herein using optically pure (enantiomerically pure) or substantially optically pure materials. Alternatively, these compounds may be obtained by resolution/separation of a mixture of stereoisomers, including racemic mixtures, using conventional procedures. Exemplary methods that may be useful for the resolution/separation of mixtures of stereoisomers include chromatography and crystallization/re-crystallization. Other useful methods may be found in "Enantiomers, Racemates, and Resolutions, "J. Jacques et al., 1981 , John Wiley and Sons, New York, NY, the disclosure of which is incorporated herein by reference. Unless otherwise provided, each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, aryl or

Het herein is independently unsubstituted or substituted with one ore more substituents defined hereinabove. The LXR modulating agents of this invention may contain a variety of accessible A ring groups, as defined above. An accessible A ring group is an aromatic heterocycle that is available by chemical synthesis and is stable. Aromatic heterocyclic groups that are suitable as A ring groups include, but are not limited to: furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl and tetrazolyl. Optionally, a N or S heteroatom of the above-mentioned heterocycles may be oxidized (forming an NO, SO, or SO₂ ring moiety) provided that such oxidation provides a stable heterocyclic moiety. In one embodiment of this invention, the A ring group is selected from oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl and tetrazolyl. In specific embodiments of the compounds of this invention, the A ring group is isoxazolyl or pyrazolyl. In the compounds of this invention, t may be 0 or 1. When t is 1 , the compound of this invention is the N-oxide of the tertiary amine, having the formula:

When t is 0, the compound of this invention is the tertiary amine having the formula:

In specific embodiments of the compounds this invention, t is 0, q is 1 and R⁴, R⁵, R⁶ and R⁷ are each H. The total number of R¹ substituents that may be present in a compound of this invention is represented by "k". In the embodiments of the compounds of this invention, k is 0, 1 or 2 and each R¹ is independently selected from -Cι-C₄ alkyl, -C₂-C₄ alkyl-NR¹²R¹³, -C₀-C₄ alkyl-COOR⁸, and -C₀-C₄ alkyl-CONR¹²R¹³. In another embodiment, each R¹ is independently selected from -C C alkyl, -C₂-C₄ alkyl-NH(Cι-C₄ alkyl), -C₂-C₄ alkyl-N(C C₄ alkyl)(Cι-C₄ alkyl),

-C₂-C₄ alkyl-NH(d-C₄ alkyl-Ar), -C₂-C₄ alkyl-N(Cι-C₄ alkyl-Ar)(Cι-C₄ alkyl), -C₂-C₄ alkyl-NH(d-C₄ alkyl-Het), -C₂-C₄ alkyl-N(Cι-C₄ alkyl-Het)(C C₄ alkyl), -C₂-C₄ alkyl-(N-Het), -C₀-C₄ alkyl-COOH, -C₀-C₄ alkyl-COOCι-C₄ alkyl, -Cι-C₄ alkyl-CONH(Cι-C₄ alkyl), -C C₄ alkyl-CON(C C₄ alkyl)(Cι-C₄ alkyl), -Cι-C₄ alkyl-CONH(Cι-C₄ alkyl-Ar), -Cι-C₄ alkyl-CON(C₁-C₄ alkyl-Ar)(C C₄ alkyl),

-d-C₄ alkyl-CONH(Cι-C₄ alkyl-Het), -C C₄ alkyl-CON(C C₄ alkyl-Het)(Cι-C₄ alkyl), and -Cι-C alkyl-CO(N-Het), where said N-Het is a heterocyclic group containing at least one nitrogen atom and the group is bonded via the nitrogen atom. In another embodiment, k is 1 or 2 and each R¹ is independently selected from -d-C₃ alkyl, -C₂-C₃ alkyl-N(C C₄ alkyl)(Cι-C₄ alkyl), -C₂-C₃ alkyl-NH(Cι alkyl-Het), -C0-C₁ alkyl-COOH, -C₀-Cι alkyl-COO-C_rC₂ alkyl,

-Cι-C₂ alkyl-CON(Cι-C₄ alkyl)(Cι-C₄ alkyl), -C C₂ alkyl-CONH(Cι alkyl-Het), and -C C₂ alkyl-CO(N-Het), where said Het is a 5-membered aromatic heterocyclic group containing one heteroatom selected from N, O and S, and said N-Het is a 5- or 6- membered saturated heterocyclic group containing at least one nitrogen atom and optionally containing one other heteroatom selected from N, O and S, wherein the group is bonded via the nitrogen atom. In specific embodiments of the compounds of this invention, k is 1 or 2 and each R¹ is independently selected from -CH₃, -CO₂CH₃, -CH₂CO₂H, -CH₂CON(CH(CH₃)₂)₂, -CH₂CONHCH₂-furan-2-yl, -CH₂CO-morpholin-4-yl, -CH₂CO-thiomorpholin-4-yl, -CH₂CO-pyrrolidin-1-yl, -CH₂CH₂N(CH(CH₃)₂)₂, and -CH₂CH₂NHCH₂-furan-2-yl. By virtue of the definitions given above for the term "alkyl", the definition of R¹ also encompasses alkyl groups that are optionally substituted with the substituents specified in the definitions above. In another embodiment, the compounds of this invention of this invention are defined wherein n is 2-4. In specific embodiments, n is 3. In another embodiment of this invention, each R² and R³ are independently selected from H and d-C₄ alkyl. When the moiety -(CR²R³)_n- is substituted and R² and R³ are different on at least one (CR²R³) moiety (e.g., when one of R² or R³ is methyl and the other of R² or R³ is hydrogen) a chiral compound is provided. All single stereoisomers, mixtures and racemates of these chiral compounds are intended to be encompassed within the broad scope of the present invention. In specific embodiments of the compounds of this invention, each R² and R³ are H. In another embodiment, the compounds of this invention of this invention are defined wherein n is 2-4. In specific embodiments, n is 3. In a preferred embodiment of this invention, Y is O. Group Q is selected from C₃-C₇ cycloalkyl, aryl and Het. By virtue of the definitions given above for the terms "cycloalkyl", "aryl" and "Het", this definition of Q also encompasses cycloalkyl, aryl and Het groups that are optionally substituted from 1 to 4 times, more preferably, from 1 to 3 times. In one embodiment of this invention, Q is an aryl group or a Het group. In other embodiments, Q is a substituted phenyl group, containing one, two or three substituents independently selected from halo, d-d alkoxy; and d-C₄ alkyl (specifically, Cι-C haloalkyl). In specific embodiments, Q is a phenyl group substituted by two substituents independently selected from chloro and trifluoromethyl, specifically Q is 2-chloro-3-trifluoromethyl-phenyl. In one embodiment of the compounds of this invention, m is 0 or 1 and R⁴ and R⁵ are independently selected from H and Cι-C₄ alkyl. In specific embodiments, m is 1 and R⁴ and R⁵ are each H. In another embodiment, W³ is H, and W¹ and W² are the same or different and are selected from Cι-C alkyl, C₃-C₆ cycloalkyl, aryl and Het. In another embodiment, m is 1 , R⁴ and R⁵ are both H, W³ is H, W¹ is phenyl and W² is Cι-C₄ alkyl or phenyl. In specific embodiments of the compounds of this invention, m is 1 , R⁴ and R⁵ are both H, W³ is H, and W¹ and W² are each unsubstituted phenyl. In other embodiments of this invention, the -C₀-C₆ alkyl- and -C₀-C alkyl- moieties of the substitutents defined herein are unsubstituted -C₀-C₆ alkyl- and unsubstituted -C₀-C alkyl- moieties, respectively. It is to be understood that the present invention covers all combinations of particular and preferred groups described hereinabove. In another embodiment, this invention is directed to a compound of Formula II:

wherein: X is O, NH or N(R¹); W¹ is unsubstituted phenyl; W² is unsubstituted d-C₄ alkyl or phenyl; W³ is H; Q is phenyl or Het, wherein said phenyl or Het is optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, Cι-C₄ alkyl, -C₀-C₄ alkyl-CO₂R⁸, -C₀-C₄ alkyl-CONR⁹R¹⁰, -C₀-C₄ alkyl-OR⁸, where said Cι-C₄ alkyl is optionally unsubstituted or substituted by one or more halo substituents, • each R¹ is H, C₁-C₄ alkyl, -C₂-C₄ alkyl-NR¹²R¹³, -C₀-C₄ alkyl-COOR⁸ or -Co-C₄ alkyl-CONR¹²R¹³; each R² and R³ is independently selected from H, fluoro and C₁-C₄ alkyl; R⁸ is selected from H, C C₄ alkyl, -C₀-C₄ alkyl-Ar, -C₀-C₄ alkyl-Het and

-C₀-C alkyl-C₃-C₇ cycloalkyl; each R⁹ and each R¹⁰ are independently selected from H and C₁-C alkyl, or R⁹ and R¹⁰ together with the nitrogen to which they are attached form a 4-7 membered heterocyclic ring which optionally contains one or more additional heteroatoms selected from N, O, and S; R¹² and R¹³ are each independently selected from H, Cι-C alkyl, -C₀-C₄ alkyl-Ar, -C₀-C alkyl-Het, -C₀-C₄ alkyl-C₃-C₇ cycloalkyl, -C₀-C₄ alkyl-S(O)_x-Ar, -C₀-C₄ alkyl-S(O)_x-Het, -C₀-C₄ alkyl-S(O)_x-C₃-C₇ cycloalkyl, -C₂-C₄ alkyl-NH-Ar, -C₂-C₄ alkyl-NH-Het, -C₂-C₄ alkyl-NH-C₃-C₇ cycloalkyl, -C₂-C₄ alkyl-N(Cι-C₄ alkyl)-Ar, -C₂-C₄ alkyl-N(Cι-C₄ alkyl)-Het, -C₂-C₄ alkyl-N(Cι-C₄ alkyl)-C₃-C₇ cycloalkyl,

-Cι-C₄ alkyl-Ar, -C₁-C alkyl-Het and -d-C alkyl-C₃-C₇ cycloalkyl, where x is 0, 1 , or 2, or R¹² and R¹³, together with the nitrogen to which they are attached, form a 4-7 membered heterocyclic ring which optionally contains one or more additional heteroatoms selected from N, O, and S; or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof. Specific embodiments of this invention comprise compounds of Formula I and

Formula II wherein k is 0, 1 or 2; n is 3; m is 1 ; q is 1 ; t is 0; R², R³, R⁴, R⁵, R⁶ and R⁷ are each H; the A ring group is selected from oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl and tetrazolyl; Y is O; each R¹ is independently selected from -C C₃ alkyl, -C₂-C₃ alkyl-N(Cι-C₄ alkyl)(d-C₄ alkyl), -C₂-C₃ alkyl-NH(Cι alkyl-Het), -C₀-Cι alkyl-COOH, -C₀-Cι alkyl-COO-Cι-C₂ alkyl, -Cι-C₂ alkyl-CON(d-C₄ alkyl)(Cι-C₄ alkyl), -C C₂ alkyl-CONH(Cι alkyl-Het), and -Cι-C₂ alkyl-CO(N-Het), where said Het is a 5-membered aromatic heterocyclic group containing one heteroatom selected from N, O and S, and said N-Het is a 5- or 6- membered saturated heterocyclic group containing at least one nitrogen atom and optionally containing one other heteroatom selected from N, O and S, wherein the group is bonded via the nitrogen atom; Q is a substituted phenyl group, containing one, two or three substituents independently selected from halo, Cι-C alkoxy; and Cι-C₄ haloalkyl; W¹ is aryl; W² is aryl or C C alkyl; and W³ is H; or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof. More specific embodiments of this invention comprise compounds of Formula I and Formula II wherein k is 1 or 2; n is 3; m is 1 ; q is 1 ; t is 0; R², R³, R⁴, R⁵, R⁶ and R⁷ are each H; each R¹ is independently selected from -CH₃, -CO₂CH₃, -CH₂CO₂H, -CH₂CON(CH(CH₃)₂)₂, -CH₂CONHCH₂-furan-2-yl, -CH₂CO-morpholin-4-yl, -CH₂CO-thiomorpholin-4-yl, -CH₂CO-pyrrolidin-1-yl, -CH₂CH₂N(CH(CH₃)₂)₂, and -CH₂CH₂NHCH₂-furan-2-yl; the A ring group is isoxazolyl or pyrazolyl; Y is O; Q is a phenyl group substituted by two substituents independently selected from chloro and trifluoromethyl; W¹ and W² are each unsubstituted phenyl; W³ is H; or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof. Compounds of this invention include: (2-chloro-3-thfluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-[3-(5-methyl-1 H-pyrazol-3- yloxy)-propyl]-amine; 3-{3-[(2-chloro-3-thfluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-5- methyl-pyrazol-1 -yl)-acetic acid; 3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-carboxylic acid methyl ester; 3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-acetic acid; 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-1-thiomorpholin-4-yl-ethanone; 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-1-morpholin-4-yl-ethanone; 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-1 -pyrrolidin-1 -yl-ethanone; 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-Λ/-furan-2-ylmethyl-acetamide; 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-Λ/,Λ/-diisopropyl-acetamide; (2-chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-[3-(5-{2-[(furan-2-ylmethyl)- amino]-ethyl}-isoxazol-3-yloxy)-propyl]-amine; 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-ethyl]-diisopropylamine; or a stereoisomer, a stereoisomeric mixture or racemate thereof and or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof. The term "LXR modulator," as used herein, means a small molecule that modulates the biological activities of LXRα and/or LXRβ. More specifically, such an LXR modulator either enhances or inhibits the biological activities of LXR on its target genes. The compounds of the Examples described herein have demonstrated at least 20% activation of LXR relative to24(S),25-epoxycholesterol in Test Method 1. It should be noted that to show activity in the specific Test Methods described herein, the LXR modulator compound must bind to the LXR nuclear receptor, thereby forming a modulator compound-bound LXR complex, which subsequently recruits the specific peptide derived from the coactivator protein, SRC1. The compounds of this invention that form an LXR- modulator compound complex and recruit SRC1 , may also recruit at least one or more of the other >80 known different nuclear receptor cofactors. Recruiter peptides derived from any of these other nuclear receptor cofactors may be similarly prepared and assayed according to known procedures. Compounds that are closely structurally related to the compounds of the Examples described herein may be prepared that do not demonstrate at least 20% recruitment of the SRC1 -derived peptide. It is anticipated, however, that such compounds will bind to LXR and that the LXR-modulator compound-complex so formed will recruit at least one or more of the other >80 known different nuclear receptor cofactors. The compounds of this invention are useful for a variety of medicinal purposes. The compounds of this invention may be used in methods for the prevention or treatment of LXR mediated diseases and conditions. This invention further provides compounds of this invention for use in the preparation of a medicament for the prevention or treatment of an LXR mediated disease or condition. LXR mediated diseases or conditions include inflammation, cardiovascular disease including atherosclerosis, arteriosclerosis, hypercholesteremia, and hyperlipidemia. In particular, the compounds of this invention are useful in the treatment and prevention of inflammation, cardiovascular disease including atherosclerosis and hypercholesteremia. The present invention also provides a method for increasing reverse cholesterol transport, compounds of this invention for increasing reverse cholesterol transport and the use of compounds of this invention for the preparation of a medicament for increasing reverse cholesterol transport. Lipoprotein metabolism is a dynamic process comprised of production of triglyceride rich particles from the liver (as VLDL), modification of these lipoprotein particles within the plasma (VLDL to IDL to LDL) and clearance of the particles from the plasma, again by the liver. This process provides the transport of triglycerides and free cholesterol to cells of the body. Reverse cholesterol transport is the proposed mechanism by which peripheral cholesterol is returned to the liver from extra-hepatic tissue. The process is carried out by HDL cholesterol. The combination of lipoprotein production (VLDL, HDL) from the liver, modification of particles (all) within the plasma and subsequent clearance back to the liver, accounts for the steady state cholesterol concentration of the plasma. Without wishing to be bound by any particular theory, it is currently believed that the compounds of this invention increase reverse cholesterol transport by increasing cholesterol efflux from the arteries. Additionally, this invention provides a method for inhibiting cholesterol absorption, compounds of this invention for inhibiting cholesterol absorption and the use of compounds of this invention for the preparation of a medicament for inhibiting cholesterol absorption. This invention also provides a method for increasing reverse cholesterol transport, compounds of this invention for increasing reverse cholesterol transport and the use of compounds of this invention for the preparation of a medicament for increasing reverse cholesterol transport. The compounds of this invention may also be useful for the prevention or treatment of inflammation and neurodegenerative diseases or neurological disorders. Accordingly, this invention also provides a method for preventing or treating inflammation (See A.J. Fowler et al., J. Invest. Dermatol., 2003 Feb., 120 (2): 246-255 and S.B. Joseph, et al. Nat. Med., 2003 Feb., 9 (2): 213-219) and a method for preventing or treating neurodegenerative diseases or neurological disorders, particularly neurodegenerative diseases or disorders characterized by neuron degeneration, neuron injury or impaired plasticity or inflammation in the CNS (as disclosed in U.S. Provisional Patent Application No. 60/368,424, filed 27 March, 2002). Particular diseases or conditions that are characterized by neuron degeneration and inflammation, and thus benefiting from the growth and/or repair of neurons include stroke, Alzheimer's disease, fronto-temporal dementias (tauopathies), peripheral neuropathy, Parkinson's disease, dementia with Lewy bodies, Huntington's disease, amyotrophic lateral sclerosis and multiple sclerosis. Diseases or conditions that are characterized by neuron degeneration and/or impaired plasticity include psychiatric disorders such as schizophrenia and depression. Particular diseases or conditions that are characterized by neuronal injury include those conditions associated with brain and/or spinal cord injury, including trauma. The methods of the present invention are useful for the treatment of animals including mammals generally and particularly humans. The present invention further provides the use of compounds of this invention for the preparation of a medicament for increasing reverse cholesterol transport. The methods of the present invention comprise the step of administering a therapeutically effective amount of the compound of this invention. As used herein, the term "therapeutically effective amount" refers to an amount of the compound of this invention that is sufficient to achieve the stated effect. Accordingly, a therapeutically effective amount of a compound of this invention used in the method for the prevention or treatment of LXR mediated diseases or conditions will be an amount sufficient to prevent or treat the LXR mediated disease or condition. Similarly, a therapeutically effective amount of a compound of this invention for use in the method of increasing reverse cholesterol transport will be an amount sufficient to increase reverse cholesterol transport. The amount of a compound of this invention or pharmaceutically acceptable salt or solvate thereof, which is required to achieve the desired biological effect will depend on a number of factors such as the use for which it is intended, the means of administration, and the recipient, and will be ultimately at the discretion of the attendant physician or veterinarian. In general, a typical daily dose for the treatment of LXR mediated diseases and conditions in a human, for instance, may be expected to lie in the range of from about 0.01 mg/kg to about 100 mg/kg. This dose may be administered as a single unit dose or as several separate unit doses or as a continuous infusion. Similar dosages would be applicable for the treatment of other diseases, conditions and therapies including increasing reverse cholesterol transport, and inhibiting cholesterol absorption. In another embodiment, the present invention provides pharmaceutical compositions comprising a compound of this invention or a pharmaceutically acceptable salt or solvate thereof, as the active ingredient, and at least one pharmaceutical carrier or diluent. These pharmaceutical compositions may be used in the prophylaxis and treatment of the foregoing diseases or conditions and in cardiovascular therapies as mentioned above. The carrier must be pharmaceutically acceptable and must be compatible with, i.e. not have a deleterious effect upon, the other ingredients in the composition. The carrier may be a solid or liquid and is preferably formulated as a unit dose formulation, for example, a tablet which may contain from 0.05 to 95% by weight of the active ingredient. Possible formulations include those suitable for oral, sublingual, buccal, parenteral (for example subcutaneous, intramuscular, or intravenous), rectal, topical including transdermal, intranasal and inhalation administration. Most suitable means of administration for a particular patient will depend on the nature and severity of the disease or condition being treated or the nature of the therapy being used and on the nature of the active compound, but where possible, oral administration is preferred for the prevention and treatment of LXR mediated diseases and conditions. Formulations suitable for oral administration may be provided as discrete units, such as tablets, capsules, cachets, lozenges, each containing a predetermined amount of the active compound; as powders or granules; as solutions or suspensions in aqueous or non-aqueous liquids; or as oil-in-water or water-in-oil emulsions. Formulations suitable for sublingual or buccal administration include lozenges comprising the active compound and, typically a flavored base, such as sugar and acacia or tragacantft and pastilles comprising the active compound in an inert base, such as gelatin and glycerine or sucrose acacia. Formulations suitable for parenteral administration typically comprise sterile aqueous solutions containing a predetermined concentration of the active compound; the solution is preferably isotonic with the blood of the intended recipient. Additional formulations suitable for parenteral administration include formulations containing physiologically suitable co-solvents and/or complexing agents such as surfactants and cyclodextrins. Oil-in-water emulsions are also suitable formulations for parenteral formulations. Although such solutions are preferably administered intravenously, they may also be administered by subcutaneous or intramuscular injection. Formulations suitable for rectal administration are preferably provided as unit-dose suppositories comprising the active ingredient in one or more solid carriers forming the suppository base, for example, cocoa butter. Formulations suitable for topical or intranasal application include ointments, creams, lotions, pastes, gels, sprays, aerosols and oils. Suitable carriers for such formulations include petroleum jelly, lanolin, polyethyleneglycols, alcohols, and combinations thereof. Formulations of the invention may be prepared by any suitable method, typically by uniformly and intimately admixing the active compound with liquids or finely divided solid carriers or both, in the required proportions and then, if necessary, shaping the resulting mixture into the desired shape. For example a tablet may be prepared by compressing an intimate mixture comprising a powder or granules of the active ingredient and one or more optional ingredients, such as a binder, lubricant, inert diluent, or surface active dispersing agent, or by molding an intimate mixture of powdered active ingredient and inert liquid diluent. Suitable formulations for administration by inhalation include fine particle dusts or mists which may be generated by means of various types of metered dose pressurized aerosols, nebulisers, or insufflators. For pulmonary administration via the mouth, the particle size of the powder or droplets is typically in the range 0.5 -10μM, preferably 1-5μM, to ensure delivery into the bronchial tree. For nasal administration, a particle size in the range 10-500μM is preferred to ensure retention in the nasal cavity. Metered dose inhalers are pressurized aerosol dispensers, typically containing a suspension or solution formulation of the active ingredient in a liquefied propellant. During use, these devices discharge the formulation through a valve adapted to deliver a metered volume, typically from 10 to 150 μL, to produce a fine particle spray containing the active ingredient. Suitable propellants include certain chlorofluorocarbon compounds, for example, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane and mixtures thereof. The formulation may additionally contain one or more co-solvents, for example, ethanol surfactants, such as oleic acid or sorbitan trioleate, anti-oxidants and suitable flavoring agents. Nebulisers are commercially available devices that transform solutions or suspensions of the active ingredient into a therapeutic aerosol mist either by means of acceleration of a compressed gas typically air or oxygen, through a narrow venturi orifice, or by means of ultrasonic agitation. Suitable formulations for use in nebulisers consist of the active ingredient in a liquid carrier and comprising up to 40% w/w of the formulation, preferably less than 20%w/w. The carrier is typically water or a dilute aqueous alcoholic solution, preferably made isotonic with body fluids by the addition of, for example, sodium chloride. Optional additives include preservatives if the formulation is not prepared sterile, for example, methyl hydroxy-benzoate, anti-oxidants, flavoring agents, volatile oils, buffering agents and surfactants. Suitable formulations for administration by insufflation include finely comminuted powders which may be delivered by means of an insufflator or taken into the nasal cavity in the manner of a snuff. In the insufflator, the powder is contained in capsules or cartridges, typically made of gelatin or plastic, which are either pierced or opened in situ and the powder delivered by air drawn through the device upon inhalation or by means of a manually-operated pump. The powder employed in the insufflator consists either solely of the active ingredient or of a powder blend comprising the active ingredient, a suitable powder diluent, such as lactose, and an optional surfactant. The active ingredient typically comprises from 0.1 to 100 w/w of the formulation. In addition to the ingredients specifically mentioned above, the formulations of the present invention may include other agents known to those skilled in the art of pharmacy, having regard for the type of formulation in issue. For example, formulations suitable for oral administration may include flavoring agents and formulations suitable for intranasal administration may include perfumes.

General Methods Compounds of Formula I and/or Formula II were prepared by methods analogous to those described in Schemes 1 - 4, as follows. Compounds of Formula I and/or II containing an isoxazolyl ring moiety may be prepared by the methods analogous to those outlined in Schemes 1 , 2 and 3.

Scheme 1

Reductive amination of the amine (2) and the aldehyde (3) yielded the secondary amine (4) which was alkylated with bromopropanol to form the tertiary amine (5) (Scheme 1). Mitsunobu reaction of 3-hydroxy-isoxazole-5-carboxylic acid methyl ester (6) and (5) yielded the isoxazole (7).

Scheme 2

Hydrolysis of the ester (7) with LiOH gave the acid (8) (Scheme 2). The acid (8) was then converted to the acyl chloride which then underwent an Arndt-Eistert reaction to form the ester (9). Next, hydrolysis of (9) with LiOH yielded the acid (10). Scheme 3

The acid (10) was treated with furan-2-yl methylamine and BOP reagent (benzotriazol-l-yloxy-tris(dimethyl-amino)phosphonium hexafluorophosphate) to yield the amide (11) (Scheme 4). The amide (11) was then converted to the corresponding amine (12) via reduction using either DiBAL-H.

Compounds of Formula I and/or II containing a pyrazolyl ring moiety may be prepared by the methods analogous to that outlined in Schemes 4.

Scheme 4

NaH, THF BrCH₂C0₂H

Treatment of tertiary amine (5), prepared according to Scheme 1 with 5-methyl- 1H-pyrazol-3-ol, provided pyrazole (13). Treatment of the sodium anion of the pyrazole (13) with bromoacetic acid yielded the acid (14) (Scheme 4). Each of the above-described methods further include the optional step(s) of forming a pharmaceutically acceptable salt of a compound of this invention, and/or of forming a pharmaceutically acceptable solvate of a compound of this invention or a pharmaceutically acceptable salt or solvate thereof.

EXAMPLES The following Test Methods and Examples are intended for illustration only and are not intended to limit the scope of the invention in any way; the present invention being defined by the claims. In the Test Methods and Examples, the following terms have the designated meaning: "pRSETa" is a known expression vector available from Invitrogen; "IPTG" means isopropyl β-D-thiogalactopyranoside; "PO " means phosphate; "PBS" means phosphate buffered saline; "TBS" means tris-buffered saline; EDTA means ethylenediamine tetraacetic acid; "DTT" means dithiothreitol; "FAF-BSA" means fatty-acid free bovine serum albumin; "SRC-1" means steroid receptor coactivator 1 ; "CS" means charcoal stripped; "nM" means nanomolar; "μM" means micromolar; "mM" means millimolar; "pM" means picomolar; "mmol" means millimoles; "g" means grams; "ng" means nanograms; "mg/ml" means milligram per milliliter; "μL" means microliters; and "mL" means milliliter.

Example 1 (2-Chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-[3-(5-methyl-1 H-pyrazol-3-yloxy)- propyl]-amine trifluoroacetic acid salt

a) Λ-(2,2-diphenylethyl)-Λ/-(2-chloro-3-trifluoromethyl-benzyl)amine To a solution of 2,2-diphenethylamine (2.0 g, 10.0 mmole) and 2-chloro-3- trifluoromethylbenzaldehyde (2.33 g, 11.0 mmole) in CH2CI2 (20 mL) was added sodium triacetoxyborohydride (2.36 g, 11.0 mmole) and AcOH (2.0 mL). The reaction mixture was stirred overnight. Solvent was removed, the residue was washed with saturated NaHCOβ, and extracted three times with EtOAc. The organic extracts were dried over Na2SO4, filtered, and concentrated. The crude mixture was subjected to column chromatography over silica gel (silica gel 60, EM Science) using 30% EtOAc.hexane as eluent to afford the title compound as a yellow oil (3.0 g, 76% yield): MS(ES) m/e 390.0 [M+H]⁺.

b) Λ/-(2,2-Diphenylethyl)-Λ/-(3-hydroxy-propyl)-/V-(2-chloro-3-trifluoromethyl-benzyl)amine To a stirring solution of 3-bromo-propanol (77 ul, 0.84 mmol) in CH3CN (10 mL) was added Nal (0.25 g, 1.7 mmol) and K2CO3 (0.23 g, 1.7 mmol). The mixture was stirred at 85 °C for 1 h, and then Λ/-(2,2-diphenylethyl)-Λ/-(2-chloro-3-trifluoromethyl- benzyl)amine (0.43 g, 1.12 mmol) was added. The reaction mixture was heated at 85 °C overnight. Solvent was removed, the residue was washed with H₂O, and extracted twice with EtOAc. The EtOAc extracts were dried over Na₂SO₄, filtered, and concentrated. The crude mixture was purified by preparative HPLC (TMC CombiPrep PDS, 75X30 mm, 25mlJmin, acetonitrile:H₂O, UV detection at 254 nm) to give 225 mg (60%) of the title compound as a white solid: MS(ES) m/e 448.0 [M+H]⁺. c) (2-Chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-[3-(5-methyl-1H-pyrazol-3- yloxy)-propyl]-amine To a solution of 5-methyl-1r/-pyrazol-3-ol (0.098 g, 1.0 mmol), polymer bound triphenylphosphine (0.411 g, 1.23 mmol, 3 mmol/g, Fluka Chemie /V-(2,2-diphenylethyl)- Λ/-(3-hydroxy-propyl)-Λ/-(2-chloro-3-trifluoromethyl-benzyl)amine (0.35 g, 0.77 mmol), and THF (10 mL), diisopropylazodicarboxylate (0.19 mL, 1.23 mmol) was added and the reaction mixture was stirred for 72h. The mixture was then filtered, concentrated, and purified via combifiash to yield the product as a yellow oil (0.10 g, 29%): MS(ES) m/e 528.2 [M+H]⁺.

Example 2 (3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-5-methyl- pyrazoI-1-yl)-acetic acid trifluoroacetic acid salt

To a solution of NaH (60% in oil)(62 mg, 1.55 mmol) and THF (1 mL), a mixture of

(2-Chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-[3-(5-methyl-1 - -pyrazol-3-yloxy)- propylj-amine (25 mg, 0.05 mmol) and THF (1 mL) was added. After the mixture stirred 0.25h, BrCH2COOH (12.0 g, 84.9 mmol) was added and the mixture was stirred overnight. The reaction mixture was poured into NH4CI and extracted with CH2CI2- The organic layers were combined, dried over a2SO4, filtered, and concentrated. Purification via preparative HPLC (TMC CombiPrep PDS, 75X30 mm, 25mlJmin, acetonitrile:H₂O:TFA, UV detection at 254 nm) yielded the (18 mg, 66%): MS(ES) m/e 586.2 [M+H]⁺. Example 3 3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-isoxazol-5- carboxylic acid methyl ester

Following the procedure of Example 1 except substituting 3-hydroxy-isoxazole-5- carboxylic acid methyl ester for 5-methyl-1H-pyrazol-3-ol in part c, the title compound was obtained as a clear oil (251 mg, 51%): MS(ES) m/e 573.2 [M+H]⁺.

Example 4 3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-isoxazol-5-yl)- acetic acid

a) 3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-isoxazol-5- carboxylic acid To a solution of 3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]- propoxy}-isoxazole-5-carboxylic acid methyl ester (116 mg, 0.2 mmol) and THF (7.5 mL) and H2O (2.5 mL), LiOH (10 mg, 0.4 mmol) was added and the reaction mixture was stirred for 12h. The mixture was concentrated and H2O was added. The mixture was acidified with 1 N HCI, extracted several times with EtOAc, and then concentrated to yield the product as a clear oil (102 mg, 92 %): MS(ES) m/e 559.2 [M+H]⁺.

b) (3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-isoxazol-5- yl)-acetic acid methyl ester To a solution of 3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]- propoxy}-isoxazole-5-carboxylic acid (97 mg, 0.17 mmol) in toluene (1.5 mL) was added SOCI₂ (102 mg, 0.86 mmol) under N₂ and the reaction mixture was stirred at 95 °C for 3.5h. All volatiles were removed under reduced pressure and TMSCHN₂ (0.3 mL, 2M in hexane) was added. After the evolution of gas ceased, MeOH (1.5 mL) and silver benzoate (39 mg, 0.17 mmol) were added and the mixture was stirred at 50 °C for 0.5 h and at RT overnight. The reaction mixture was filtered and concentrated to give a crude oil which was purified by silica gel chromatography to give pure product as a yellow oil (26 mg, 26%): MS(ES) m/e 587.2 [M+H]⁺. c) (3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-isoxazol-5- yl)-acetic acid. To a solution of (3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]- propoxy}-isoxazole-5-yl)-acetic acid methyl ester (26 mg, 0.05 mmol) and THF (1.5 mL) and H2O (0.5 mL), LiOH (2.0 mg, 0.09 mmol) was added and the reaction mixture was stirred for 12h. The mixture was concentrated and H2O was added. The mixture was acidified with 1 N HCI, extracted several times with EtOAc, and then concentrated to yield the product as a yellow oil (25 mg, 100 %): MS(ES) m/e 573.2 [M+H]⁺. Example 5

2-(3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-isoxazol-5- yl)-1-thiomorpholin-4-yl-ethanone

To a solution of (3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]- propoxy}-isoxazol-5-yl)-acetic acid (32 mg, 0.06 mmol), thiomorpholine (6 mg, 0.06 mmol), and CH₃CN (1 mL), benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent) (28.4 mg, 0.06 mmol) was added and the mixture stirred overnight. The mixture was concentrated, washed with 1N HCI and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated to give the product as a yellow oil (35 mg, 96%): MS(ES) m/e 658.0 [M+H]⁺.

Example 6 2-(3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-isoxazol-5- yl)-1 -morpholin-4-yl-ethanone

Following the procedure of Example 5 except substituting morpholine for thiomorpholine, the title compound was obtained as a yellow oil (25 mg, 100 %): MS(ES) m/e 642.2 [M+H]⁺. Example 7 2-(3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-isoxazol-5- yl)-1-pyrrolidin-1-yl-ethanone

Following the procedure of Example 5 except substituting pyrrolidine for thiomorpholine, the title compound was obtained as a yellow oil (35 mg, 90%): MS(ES) m/e

626.2 [M+H]⁺ . Example 8

2-(3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-isoxazol-5- yl)-Λ/-furan-2-ylmethyl-acetamide

Following the procedure of Example 5 except substituting furan-2-yl methylamine for thiomorpholine, the title compound was obtained as a yellow oil (39 mg, 100%): MS(ES) m/e 652.2 [M+H]⁺.

Example 9 2-(3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-isoxazol-5- yl)-Λ/,Λ/-diisopropyl-acetamide

Following the procedure of Example 5 except substituting diisopropylamine for thiomorpholine, the title compound was obtained as a clear oil (34 mg, 54%): MS(ES) m/e 656.2 [M+H]⁺. Example 10 (2-Chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-[3-(5-{2-[(furan-2-ylmethyl)-amino]- ethyl}-isoxazol-3-yloxy)-propyl]-amine

To a solution of 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl- amino]-propoxy}-isoxazol-5-yl)-Λ/-furan-2-ylmethyl-acetamide (23 mg, 0.035 mmol) and toluene (0.5 mL), DIBAL-H (1.5 M in toluene)(0.06 mL, 0.09 mmol) was added at -78 °C and the mixture was stirred for 12h at RT. A saturated solution of Rochelle's salt was added and the mixture stirred for 5h. The mixture was then poured into a saturated

NH4CI and extracted with EtOAc. The organic layer was dried over Na SO4, filtered, and concentrated. Purification via preparative HPLC (TMC CombiPrep PDS, 75X30 mm, 25mL/min, acetonitrile:H₂O:TFA, UV detection at 254 nm) yielded the product as a clear oil (3 mg, 12%): MS(ES) m/e 638.2 [M+H]⁺ .

Example 11 2-(3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-ethyl]-diisopropylamine

Following the procedure of Example 10 except substituting 2-(3-{3-[(2-chloro-3- trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-isoxazol-5-yl)-A ,Λ/-diisopropyl- acetamide for 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]- propoxy}-isoxazol-5-yl)-Λ/-furan-2-ylmethyl-acetamide, the title compound was obtained as a clear oil (30 mg, 82%): MS(ES) m/e 642.2 [M+H]⁺.

Biological Testing The LXRα and LXRβ activity of the compounds described herein were determined using the following assay methods. Test Method 1 : Ligand Sensing Assay (LiSA) for LXRβ Agonist Activity This assay measures the recruitment of a peptide derived from the coactivator protein, SRC1 , to the agonist-bound LXRβ. Peptides derived from other nuclear receptor cofactors may be similarly prepared and assayed. To generate the human LXRβ ligand binding domain suitable for LiSA, a modified polyhistidine tag (MKKGHHHHHHG) (SEQ ID No. 1) was fused in frame to the human LXRβ ligand binding domain (amino acids 185-461 of Genbank accession number U07132) and subcloned into the expression vector pRSETa (Invitrogen) under the control of an IPTG inducible T7 promoter. The human LXRβ ligand binding domain was expressed in E. coli strain BL21 (DE3). Ten-liter fermentation batches were grown in Rich PO media with 0.1 mg/mL Ampicillin at 25°C for 12 hours, cooled to 9°C and held at that temperature for 36 hours to a density of OD600=14. At this cell density, 0.25 mM IPTG was added and induction proceeded for 24 hours at 9°C, to a final OD600 = 16. Cells were harvested by centrifugation (20 minutes, 3500g, 4°C), and concentrated cell slurries were stored in PBS at -80°C. Typically 25-50 g of cell paste is resuspended in 250-500 mL TBS, pH 8.0 (25mM Tris, 150 mM NaCl). Cells are lysed by passing 3 times through an APV Rannie MINI-lab homogenizer and cell debris is removed by centrifugation (30 minutes, 20,000g, 4°C). The cleared supernatant is filtered through coarse pre-filters, and TBS, pH 8.0, containing 500 mM imidazole is added to obtain a final imidazole concentration of 50mM. This lysate is loaded onto a column (XK-26, 10 cm) packed with Sepharose [Ni++ charged] Chelation resin (available from Pharmacia) and pre-equilibrated with TBS pH 8.0/ 50mM imidazole. After washing to baseline absorbance with equilibration buffer, the column is washed with approximately one column volume of TBS pH -8.0 containing 95mM imidazole.

LXRβLBD(185-461) is eluted with a gradient from 50 to 500 mM imidazole. Column peak fractions are pooled immediately and diluted 5 fold with 25 mM Tris pH 8.0, containing 5% 1 ,2-propanediol, 0.5mM EDTA and 5mM DTT. The diluted protein sample is then loaded onto a column (XK-16, 10cm) packed with Poros HQ resin (anion exchange). After washing to baseline absorbance with the dilution buffer the protein is eluted with a gradient from 50 -500 mM NaCl. Peak fractions are pooled and concentrated using Centri-prep 10K (Amicon) filter devices and subjected to size exclusion, using a column (XK-26, 90 cm) packed with Superdex-75 resin (Pharmacia) pre-equilibrated with TBS, pH 8.0, containing 5 % 1 ,2-propanediol, 0.5mM EDTA and 5mM DTT. LXRβ protein was diluted to approximately 10μM in PBS and five-fold molar excess of NHS-LC-Biotin (Pierce) was added in a minimal volume of PBS. This solution was incubated with gentle mixing for 30 minutes at ambient room temperature. The biotinylation modification reaction was stopped by the addition of 2000x molar excess of Tris-HCl, pH 8. The modified LXRβ protein was dialyzed against 4 buffer changes, each of at least 50 volumes, PBS containing 5mM DTT, 2mM EDTA and 2% sucrose. The biotinylated LXRβ protein was subjected to mass spectrometric analysis to reveal the extent of modification by the biotinylation reagent. In general, approximately 95% of the protein had at least a single site of biotinylation; and the overall extent of biotinylation followed a normal distribution of multiple sites, ranging from one to nine. The biotinylated protein was incubated for 20-25 minutes at a concentration of 5nM in assay buffer (50mM NaF, 50mM MOPS-pH 7.5, 0.1 mg/ml FAF-BSA, 0.05mM CHAPS, 10mM DTT) with equimolar amounts of streptavidin-AlloPhycoCyanin (APC, Molecular Probes). At the same time, the biotinylated peptide comprising amino acids 676-700 of SRC-1 (CPSSHSSLTERHKILHRLLQEGSPS-CONH2) (SEQ ID No. 2) at a concentration of 10nM was incubated in assay buffer with a ^ΛA molar amount of streptavidin-labelled Europium (Wallac) for 20-25 minutes. After the initial incubations are completed, a 20 molar excess of biotin was added to each of the solutions to block the unattached streptavidin reagents. After 20 min at room temp, the solutions were mixed yielding a concentration of 5nM for the dye-labeled LXR protein and 10nM for SRC-1 peptide. 49uL of the protein/peptide mixture was added to each well of an assay plate containing 1ul of test compound serial diluted in 100% DMSO. The final volume in each well was 0.05mL, and the concentration in the well for the dye-labeled protein and peptide was 5nM protein and 10nM SRC1 -peptide. The final test compound concentrations were between 33pM and 20uM. The plates were incubated at room temp 2-hours and then counted on a Wallac Victor V fluorescent plate reader. In this assay 1μM 24(S), 25-epoxycholesterol gave a reading of 20000 fluorescence units over a background reading of 10000 fluorescence units.

Test Method 2: Ligand Sensing Assay for LXRα Agonist Activity The assay for LXRα was run according to the procedures of Test Method 1 , above using his-tagged LXRα ligand binding domain (amino acids 183-447 of Genbank accession number U22662 , with the 14^th amino acid corrected to A from R). In this assay 1μM 24(S),25-epoxycholesterol gave a reading of 20000 fluorescence units over a background reading of 10000 fluorescence units. Where indicated below, various compounds were purified by Combifiash chromatography which was generally conducted on silica gel using ethyl acetate/hexane (gradient: 5:95-50:50)).

The above description fully discloses how to make and use the present invention. However, this invention is not limited to the particular embodiments described hereinabove, but includes all modification thereof within the scope of the appended claims and their equivalents. Those skilled in the art will recognize through routine experimentation that various changes and modifications can be made without departing from the scope of this invention. The various references to journals, patents and other patent applications that are cited herein are incorporated by reference herein as though fully set forth.

Claims

What is claimed is:

1. A compound of Formula I:

wherein: the A ring is an accessible 5-membered aromatic heterocyclic group comprising 1 ,

2 or 3 heteroatoms each independently selected from N, O or S, wherein the N or S heteroatom is optionally oxidized; Y is selected from -O-, -S-, -N(R⁸)-, and -C(R²)(R³)-; W¹ is selected from C₃-C₈ cycloalkyl, aryl and Het, wherein said C₃-C₈ cycloalkyl, aryl and Het are optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, Ci-Ce alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, -Co-C₆ alkyl-CO₂R⁸, -C₀-C₆ alkyl-C(O)SR⁸, -C₀-C₆ alkyl-CONR⁹R¹⁰, -C₀-C₆ alkyl-COR¹¹, -Co-Ce alkyl-NR⁹R¹⁰, -C₀-C₆ alkyl-SR⁸, -C₀-C₆ alkyl-OR⁸, -C₀-C₆ alkyl-SO₃H, -Co-C₆ alkyl-SO₂NR⁹R¹⁰, -C₀-C₆ alkyl-SO₂R¹⁴, -C₀-C₆ alkyl-SOR¹¹, -C₀-C₆ alkyl-OCOR¹¹, -C₀-C₆ alkyl-OC(O)NR⁹R¹⁰, -C₀-C₆ alkyl-OC(O)OR¹¹, -C₀-C₆ alkyl-NR¹⁵C(O)OR¹¹, -Co-C₆ alkyl-NR¹⁵C(O)NR⁹R¹⁰, and -C₀-C₆ alkyl-NR ⁵COR¹¹, where said Cι-C₆ alkyl, is optionally unsubstituted or substituted by one or more halo substituents; W² is selected from H, halo, d-Ce alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, -Co-C₆ alkyl-NR⁹R¹⁰, -C₀-C₆ alkyl-SR⁸, -C₀-C₆ alkyl-OR⁸, -C₀-C₆ alkyl-CO₂R⁸,

-Co-Ce alkyl-C(O)SR⁸, -C₀-C₆ alkyl-CONR⁹R¹⁰, -C₀-C₆ alkyl-COR¹¹, -C₀-C₆ alkyl-OCOR¹¹, -Co-Ce alkyl-OCONR⁹R¹⁰, -C₀-C₆ alkyl-NR¹⁵CONR⁹R¹⁰, -C₀-C₆ alkyl-NR¹⁵COR¹¹, -Co-Ce alkyl-Het, -C₀-C₆ alkyl-Ar and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl, wherein said d-C₆ alkyl is optionally unsubstituted or substituted by one or more halo substituents, and wherein the C₃-C₇ cycloalkyl, Ar and Het moieties of said -C₀-C₆ alkyl-Het, -C₀-C₆ alkyl-Ar and -Co-C₆ alkyl-C₃-C₇ cycloalkyl are optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, Ci-Ce alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, -C₀-C₆ alkyl-CO₂R⁸, -C₀-C₆ alkyl-C(O)SR⁸, -C₀-C₆ alkyl-CONR⁹R¹⁰, -Co-Ce alkyl-COR¹¹, -C₀-C₆ alkyl-NR⁹R¹⁰, -C₀-C₆ alkyl-SR⁸, -C₀-C₆ alkyl-OR⁸, -Co-Ce alkyl-SO₃H, -C₀-C₆ alkyl-SO₂NR⁹R¹⁰, -C₀-C₆ alkyl-SO₂R¹⁴, -C₀-C₆ alkyl-SOR¹¹, -Co-Ce alkyl-OCOR¹¹, -C₀-C₆ alkyl-OC(O)NR⁹R¹⁰, -C₀-C₆ alkyl-OC(O)OR¹¹, -Co-Ce alkyl-NR¹⁵C(O)OR¹¹, -C₀-C₆ alkyl-NR¹⁵C(O)NR⁹R¹⁰, and -C₀-C₆ alkyl-NR¹⁵COR¹¹, where said Cι-C₆ alkyl, is optionally unsubstituted or substituted by one or more halo substituents; W³ is selected from H, halo, C C₆ alkyl, -C₀-C₆ alkyl-NR⁹R¹⁰, -C₀-C₆ alkyl-SR⁸,

-Co-Ce alkyl-OR⁸, -C₀-C₆ alkyl-CO₂R⁸, -C₀-C₆ alkyl-C(O)SR⁸, -C₀-C₆ alkyl-CONR⁹R¹⁰, -Co-Ce alkyl-COR¹¹, -C₀-C₆ alkyl-OCOR¹¹, -C₀-C₆ alkyl-OCONR⁹R¹⁰, -Co-Ce alkyl-NR¹⁵CONR⁹R¹⁰, -C₀-C₆ alkyl-NR¹⁵COR¹¹, -C₀-C₆ alkyl-Het, -Cι-C₆ alkyl-Ar and -Cι-C₆ alkyl-C₃-C₇ cycloalkyl, wherein said Cι-C₆ alkyl is optionally unsubstituted or substituted by one or more halo substituents; Q is selected from C₃-C₈ cycloalkyl, Ar and Het; wherein said C₃-C₈ cycloalkyl, Ar and Het are optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, Ci-Ce alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, -Co-C₆ alkyl-CO₂R⁸, -C₀-C₆ alkyl-C(O)SR⁸, -C₀-C₆ alkyl-CONR⁹R¹⁰, -C₀-C₆ alkyl-COR¹¹, -Co-Ce alkyl-NR⁹R¹⁰, -C₀-C₆ alkyl-SR⁸, -C₀-C₆ alkyl-OR⁸, -C₀-C₆ alkyl-SO₃H,

-Co-C₆ alkyl-SO₂NR⁹R¹⁰, -C₀-C₆ alkyl-SO₂R¹⁴, -C₀-C₆ alkyl-SOR¹¹, -C₀-C₆ alkyl-OCOR¹¹, -Co-Ce alkyl-OC(O)NR⁹R¹⁰, -C₀-C₆ alkyl-OC(O)OR¹¹, -C₀-C₆ alkyl-NR¹⁵C(O)OR¹¹, -Co-Ce alkyl-NR¹⁵C(O)NR⁹R¹⁰, and -C₀-C₆ alkyl-NR¹⁵COR¹¹, where said d-C₆ alkyl is optionally unsubstituted or substituted by one or more halo substituents; k is O, 1 or 2; n is 2-8; m is O or 1 ; q is 0 or 1 ; t is 0 or 1 ; each R¹ is the same or different and is independently selected from halo, cyano, nitro, oxo, Cι-Cι₂ alkyl, -C₂-Ci₂ alkenyl, -C₂-C₄ alkyl -OR⁸, -C₂-C₄ alkyl-NR¹²R¹³, -Cι-C₄ alkyl-CN, -C₀-C₄ alkyl-COOR⁸, -C₀-C₄ alkyl-COR¹¹, -C₂-C₄ alkyl-OCOR¹¹, -d-d alkyl-CONR¹²R¹³, -C₂-C₄ alkyl-N(R¹⁵)COR¹¹, -C₀-C₄ alkyl-SO₃H, -C₀-C₄ alkyl-SO₂R¹⁴, -C₀-C₄ alkyl-SO₂NR⁹R¹⁰, -C₀-C₄-C(=NR¹⁵)NR⁹R¹⁰, -C₂-C₄ alkyl-N(R¹⁵)SO₂R¹⁴, and -C C₄ alkyl-Het, where Het is a 5 or 6-membered heterocyclic group; each R² and R³ is independently selected from H, halo, d-C₆ alkyl, -Co-Ce alkyl-Het, -C₀-C₆ alkyl-Ar and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl; R⁴ and R⁵ are each independently selected from H, halo, d-C₆ alkyl, -Co-Ce alkyl-Het, -C₀-C₆ alkyl-Ar and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl; R⁶ and R⁷ are each independently selected from H, halo, C C₆ alkyl, -C₀-C₆ alkyl-Het, -C₀-C₆ alkyl-Ar and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl; R⁸ is selected from H, Cι-C₆ alkyl, C₃-C_β alkenyl, C₃-C₆ alkynyl, -C₀-C₆ alkyl-Ar, -Co-C₆ alkyl-Het and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl; each R⁹ and each R¹⁰ are independently selected from H, d-C₆ alkyl,

C₃-C₆ alkenyl, C₃-C₆ alkynyl, -C₀-C₆ alkyl-Ar, -C₀-C₆ alkyl-Het and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl, or R⁹ and R¹⁰ together with the nitrogen to which they are attached form a 4-7 membered heterocyclic ring which optionally contains one or more additional heteroatoms selected from N, O, and S; R¹¹ is selected from Cι-C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, -C₀-C₆ alkyl-Ar,

-Co-C₆ alkyl-Het and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl; R¹² and R¹³ are each independently selected from H, d-C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, -C₀-C₆ alkyl-Ar, -C₀-C₆ alkyl-Het, -C₀-C₆ alkyl-C₃-C₇ cycloalkyl, -Co-C₆ alkyl-O-Ar, -C₀-C₆ alkyl-O-Het, -C₀-C₆ alkyl-O-C₃-C₇ cycloalkyl, -Co-Ce alkyl-S(O)_x-Cι-C₆ alkyl, -C₀-C₆ alkyl-S(O)_x-Ar, -C₀-C₆ alkyl-S(O)_x-Het, -Co-Ce alkyl-S(O)_x-C₃-C₇ cycloalkyl, -C₀-C₆ alkyl-NH-Ar, -C₀-C₆ alkyl-NH-Het, -Co-C₆ alkyl-NH-C₃-C₇ cycloalkyl, -C₀-C₆ alkyl-N(Cι-C₄ alkyl)-Ar, -Co-C₆ alkyl-N(C C₄ alkyl)-Het, -C₀-C₆ alkyl-N(d-C₄ alkyl)-C₃-C₇ cycloalkyl, -C₀-C₆ alkyl-Ar, -C₀-C₆ alkyl-Het and -C₀-C₆ alkyl-C₃-C₇ cycloalkyl, where x is 0, 1 or 2, or R¹² and R¹³, together with the nitrogen to which they are attached, form a 4-7 membered heterocyclic ring which optionally contains one or more additional heteroatoms selected from N, O, and S, wherein said d-C₆ alkyl is optionally substituted by one or more of the substituents independently selected from halo, -OH, -SH, -NH₂, -NH(unsubstituted Cι-C₆ alkyl), -N(unsubstituted d-C₆ alkyl)(unsubstituted d-C₆ alkyl), unsubstituted -OCι-C₆ alkyl, -CO₂H, -CO₂(unsubstituted Ci-Ce alkyl), -CONH₂, -CONH(unsubstituted d-Ce alkyl), -CON(unsubstituted Ci-Ce alkyl)(unsubstituted d-C₆ alkyl), -SO₃H, -SO₂NH₂, -SO₂NH(unsubstituted d-C₆ alkyl) and -SO₂N(unsubstituted Ci-Ce alkyl)(unsubstituted Ci-C₆ alkyl); R¹⁴ is Cι-C₆ alkyl, -C₀-C₆ alkyl-C₃-C₇ cycloalkyl, -C₀-C₆ alkyl-Ar or -C₀-C₆ alkyl-Het; and R¹⁵ is H, Cι-C₆ alkyl, -C₀-C₆ alkyl-C₃-C₇ cycloalkyl, -C₀-C₆ alkyl-Ar or -C₀-C₆ alkyl-Het; or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof.

2. The compound according to claim 1 , wherein t is 0.

3. The compound according to claim 1 or claim 2, wherein k is 1 or 2.

4. The compound according to any one of claims 1-3, wherein Y is O.

5. The compound according to any one of claims 1-4, wherein each R¹ is independently selected from -Cι-C₄ alkyl, -C₂-C₄ alkyl-NR¹²R¹³, -C₀-C₄ alkyl-COOR⁸, and -C₀-C₄ alkyl-CONR¹²R¹³.

6. The compound according to any one of claims 1-5, wherein each R¹ is independently selected from -Cι-C₄ alkyl, -C₂-C alkyl-NH(Cι-C alkyl), -C₂-C₄ alkyl-N(Cι-C₄ alkyl)(C C₄ alkyl), -C₂-C₄ alkyl-NH(Cι-C₄ alkyl-Ar),

-C₂-C₄ alkyl-N(Cι-C₄ alkyl-Ar)(Cι-C₄ alkyl), -C₂-C₄ alkyl-NH(Cι-C₄ alkyl-Het),

-C₂-C₄ alkyl-N(Cι-C₄ alkyl-Het)(Cι-C₄ alkyl), -C₂-C₄ alkyl-(N-Het), -C₀-C₄ alkyl-COOH,

-d-d alkyl-COOCι-C₄ alkyl, -Cι-C₄ alkyl-CONH(Cι-C₄ alkyl),

-Cι-C₄ alkyl-CON(d-C₄ alkyl)(d-C₄ alkyl), -d-C₄ alkyl-CONH(Cι-C₄ alkyl-Ar), -d-d alkyl-CON(Cι-C₄ alkyl-Ar)(Cι-C₄ alkyl), -C C₄ alkyl-CONH(Cι-C₄ alkyl-Het),

-d-C₄ alkyl-CON(Cι-C₄ alkyl-Het)(Cι-C₄ alkyl), and -Cι-C₄ alkyl-CO(N-Het), where said N- Het is a heterocyclic group containing at least one nitrogen atom and the group is bonded via the nitrogen atom.

7. The compound according to any one of claims 1-6, wherein n is 2-4.

8. The compound according to any one of claims 1-7, wherein n is 3.

9. The compound according to any one of claims 1-8, wherein q is 1.

10. The compound according to any one of claims 1-9, wherein R⁶ and R⁷ are each H.

11. The compound according to any one of claims 1-10, wherein Q is aryl.

12. The compound according to any one of claims 1-11 , wherein Q is 2-chloro- 3-trifluoromethyl-phenyl.

13. The compound according to any one of claims 1-12, wherein m is 1 and R⁴ and R⁵ are both H.

14. The compound according to any one of claims 1-13, wherein W³ is H

15. The compound according to any one of claims 1-14 wherein W¹ and W² are each unsubstituted phenyl.

16. A compound of Formula II:

wherein: X is O, NH or N(R¹); W¹ is unsubstituted phenyl; W² is unsubstituted Cι-C₄ alkyl or phenyl; W³ is H; Q is phenyl or Het, wherein said phenyl or Het is optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, Cι-d alkyl, -C₀-C₄ alkyl-CO₂R⁸, -C₀-C₄ alkyl-CONR⁹R¹⁰, -C₀-C₄ alkyl-OR⁸, where said C C₄ alkyl is optionally unsubstituted or substituted by one or more halo substituents, each R¹ is H, Cι-C₄ alkyl, -C₂-C₄ alkyl-NR¹²R¹³, -C₀-C₄ alkyl-COOR⁸ or -C₀-C₄ alkyl-CONR¹²R¹³; each R² and R³ is independently selected from H, fluoro and d-C alkyl; R⁸ is selected from H, C C₄ alkyl, -C₀-C₄ alkyl-Ar, -C₀-C₄ alkyl-Het and

-C₀-C₄ alkyl-C₃-C₇ cycloalkyl; each R⁹ and each R¹⁰ are independently selected from H and d-C alkyl, or R⁹ and R¹⁰ together with the nitrogen to which they are attached form a 4-7 membered heterocyclic ring which optionally contains one or more additional heteroatoms selected from N, O, and S; R¹² and R¹³ are each independently selected from H, Cι-C₄ alkyl, -C₀-C alkyl-Ar, -d-d alkyl-Het, -C₀-C₄ alkyl-C₃-C₇ cycloalkyl, -C₀-C₄ alkyl-S(O)_x-Ar, -d-d alkyl-S(O)_x-Het, -C₀-C₄ alkyl-S(O)_x-C₃-C₇ cycloalkyl, -C₂-C₄ alkyl-NH-Ar, -C₂-C₄ alkyl-NH-Het, -C₂-C₄ alkyl-NH-C₃-C₇ cycloalkyl, -C₂-C₄ alkyl-N(Cι-C₄ alkyl)-Ar, -C₂-C₄ alkyl-N(Cι-C₄ alkyl)-Het, -C₂-C₄ alkyl-N(C C₄ alkyl)-C₃-C₇ cycloalkyl,

-Cι-C₄ alkyl-Ar, -C C₄ alkyl-Het and -d-C alkyl-C₃-C₇ cycloalkyl, where x is 0, 1 , or 2, or R¹² and R¹³, together with the nitrogen to which they are attached, form a 4-7 membered heterocyclic ring which optionally contains one or more additional heteroatoms selected from N, O, and S; or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof.

17. The compound according to claim 1, wherein k is 0, 1 or 2; n is 3; m is 1; q is 1 ; t is 0; R², R³, R⁴, R⁵, R⁶ and R⁷ are each H; the A ring group is selected from oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl and tetrazolyl; Y is O; each R is independently selected from -Cι-C₃ alkyl, -C₂-C₃ alkyl-N(Cι-C₄ alkyl)(Cι-C₄ alkyl), -C₂-C₃ alkyl-NH(Cι alkyl-Het), -C₀-C₁ alkyl-COOH, -d-d alkyl-COO-C C₂ alkyl, -Cι-C₂ alkyl-CON(Cι-C₄ alkyl)(C C₄ alkyl), -C C₂ alkyl-CONH(Cι alkyl-Het), and -Cι-C₂ alkyl-CO(N-Het), where said Het is a 5- membered aromatic heterocyclic group containing one heteroatom selected from N, O and S, and said N-Het is a 5- or 6-membered saturated heterocyclic group containing at least one nitrogen atom and optionally containing one other heteroatom selected from N, O and S, wherein the group is bonded via the nitrogen atom; Q is a substituted phenyl group, containing one, two or three substituents independently selected from halo, d-d alkoxy; and d-C haloalkyl; W¹ is aryl; W² is aryl or Cι-C₄ alkyl; and W³ is H; or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof.

18. The compound according to claim 17, wherein k is 1 or 2; n is 3; m is 1; q is 1 ; t is 0; R², R³, R⁴, R⁵, R⁶ and R⁷ are each H; each R¹ is independently selected from -CH₃, -CO₂CH₃, -CH₂CO₂H, -CH₂CON(CH(CH₃)₂)₂, -CH₂CONHCH₂-furan-2-yl, -CH₂CO-morpholin-4-yl, -CH₂CO-thiomorpholin-4-yl, -CH₂CO-pyrrolidin-1-yl, -CH₂CH₂N(CH(CH₃)₂)₂, and -CH₂CH₂NHCH₂-furan-2-yl; the A ring group is isoxazolyl or pyrazolyl; Y is O; Q is a phenyl group substituted by two substituents independently selected from chloro and trifluoromethyl; W¹ and W² are each unsubstituted phenyl; W³ is H; or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof.

19. A compound selected from: (2-chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-[3-(5-methyl-1H-pyrazol-3- yloxy)-propyl]-amine; 3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-5- methyl-pyrazol-1-yl)-acetic acid; 3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-carboxylic acid methyl ester; 3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-acetic acid; 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-1-thiomorpholin-4-yl-ethanone; 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-1-morpholin-4-yl-ethanone; 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-1 -pyrrolidin-1 -yl-ethanone; 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-Λ/-furan-2-ylmethyl-acetamide; 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-/V,Λ/-diisopropyl-acetamide; (2-chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-[3-(5-{2-[(furan-2-ylmethyl)- amino]-ethyl}-isoxazol-3-yloxy)-propyl]-amine; 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}- isoxazol-5-yl)-ethyl]-diisopropylamine; or a stereoisomer, a stereoisomeric mixture or racemate thereof and a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof.

20. A pharmaceutical composition comprising the compound according to any one of claims 1-19.

21. The pharmaceutical composition according to claim 20 further comprising a pharmaceutically acceptable carrier or diluent.

22. A method for the prevention or treatment of an LXR mediated disease or condition comprising administering a therapeutically effective amount of the compound according to any one of claims 1 -19.

23. The method according to claim 22, wherein said LXR mediated disease or condition is cardiovascular disease.

24. The method according to any one of claims 22-23, wherein said LXR mediated disease or condition is atherosclerosis.

25. The method according to any one of claims 22-24, wherein said LXR mediated disease or condition is inflammation.

26. A method for increasing reverse cholesterol transport, said method comprising administering a therapeutically effective amount of the compound according to any one of claims any one of claims 1-19.

27. A method for inhibiting cholesterol absorption, said method comprising administering a therapeutically effective amount of the compound according to any one of claims any one of claims 1-19.

28. A compound according to any one of claims 1-19 for use as a medicament.

29. Use of a compound according to any one of claims 1-19 for the preparation of a medicament for the prevention or treatment of an LXR mediated disease or condition.

30. Use of a compound according to any one of claims 1-19 for the preparation of a medicament for the prevention or treatment of cardiovascular disease.

31. Use of a compound according to any one of claims 1-19 for the preparation of a medicament for the prevention or treatment of atherosclerosis.

32. Use of a compound according to any one of claims 1-19 for the preparation of a medicament for the prevention or treatment of inflammation.

33. Use of a compound according to any one of claims 1-19 for the preparation of a medicament for increasing reverse cholesterol transport.

34. Use of a compound according to any one of claims 1 -19 for the preparation of a medicament for inhibiting cholesterol absorption.

35. A pharmaceutical composition comprising a compound according to any one of claims 1-19 for use in the prevention or treatment of an LXR mediated disease or condition.