US 9,751,869 B2 · LXR modulators

Abstract

The present invention provides compounds of Formula I and Formula II: or pharmaceutically acceptable salts or solvates thereof, as modulators of liver X receptors (LXRs), and compositions comprising any of such novel compounds and methods of use thereof. These compounds are useful as medicaments for treatment and/or prophylaxis for diseases or conditions related to activity of LXRs.

A compound of the formula I or II,

or a pharmaceutically acceptable salt or solvate thereof, wherein
Ring C is selected from oxazolyl and triazolyl;
Ring D is selected from phenyl and pyridyl;
A is phenyl or a 5 or 6 membered heteroaryl, wherein the phenyl is optionally fused to a 5 or 6 membered heterocyclyl or 5 or 6 membered heteroaryl, wherein A is optionally substituted with 1, 2, or 3 RA groups, wherein
each RA is independently RA1, —C1-C6alkyl-RA1, C1-C6alkyl, C1-C6 haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, pyrrolidinone, or pyrrolidinyl, wherein the cycloalkyl is optionally substituted with 1, 2, 3, or 4 groups that are independently RA1, C1-C6alkyl, or —C1-C6alkyl-RA1, wherein
each RA1 is independently halogen, cyano, nitro, —OR, —NR2, —SR, —C(O)R, or —C(O)OR;
alternatively, two RA's on adjacent carbons can join to form a —O—CH2—O—, —O—CH2—CH2—, —O—CH2—CH2—O—, —CH2—CH2—CH2—, or —O—CF2—O—;
RB1 is hydrogen, C1-3alkyl, halo, cyclopropyl, or C1-3haloalkyl;
RB2 is hydrogen, halo, —CN, —C(O)NR2, or C1-3alkyl;
RB3 is C1-6alkyl, C1-6haloalkyl, or C3-6cycloalkyl, each of which is substituted with 0-1 RB5;
hydrogen;
cyano;
—C(O)—R;
—C(O)NR2;
—NHC(O)R;
—NHSO2R;
or a 5-membered ring heteroaryl, wherein the heteroaryl ring consists of carbon atoms and 1, 2, or 3 heteroatoms independently selected from the group consisting of N, S, and O and is substituted with 0-1 R;
RB4 is H, halogen, C1-3alkyl, C1-3haloalkyl, —C3-C6cycloalkyl, or —O—C1-3alkyl;
RB5 is cyano, —O—R, —C(O)NR2, —C(O)OR, —NR2, —OC(O)—NH2, —S(O)2NR2, or a 5-membered ring heteroaryl, wherein the heteroaryl ring consists of carbon atoms and 1, 2, or 3 heteroatoms independently selected from the group consisting of N, S, and O;
RC is hydrogen, halogen, cyano, or nitro;
n is 0, 1, 2, 3, or 4;
and
each RD1 and RD2 are independently RD3, C1-C6alkyl, —C1-C6alkyl-RD3, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, or C3-C8cycloalkyl, wherein the cycloalkyl is each optionally substituted with 1, 2, 3, or 4 groups that are independently RD3, C1-C6alkyl, C3-C6cycloalkyl, or —C1-C6alkyl-RD3, wherein
each RD3 is independently halogen, cyano, —OR, —NR2, —SR, —C(O)R, —C(O)OR, —C(O)NR2, —S(O)R, —S(O)2R, —S(O)NR2, —S(O)2NR2, —OC(O)R, —OC(O)OR, —OC(O)NR2, —N(R)C(O)R, —N(R)C(O)OR, —N(R)C(O)NR2, —N(R)S(O)2R, —N(R)S(O)2OR, —N(R)S(O)2NR2, or —S(O)2N(R)C(O)NR2;
and
RL is hydrogen, C1-C6alkyl, C3-C6cycloalkyl, C1-C6haloalkyl, —C(O)R, —C(O)OR, —C(O)NR2, —S(O)R, —S(O)2R, —S(O)OR, —S(O)2OR, —S(O)NR2, or —S(O)2NR2;
wherein
each R group is independently hydrogen, C1-C6alkyl, —C1-C6alkyl-R2, C1-C6haloalkyl, —C1-C6haloalkyl-R2, C2-C6alkenyl, C2-C6alkynyl, or C3-C8cycloalkyl, or —C1-C6alkyl-C3-6cycloalkyl;
or for any —C(O)NR2 or —NR2, alternatively, the two Rs along with the N to which they attach may form morpholinyl, pyrrolidinyl, or piperdinyl;
and
wherein
each R2 is independently cyano, —OR3, —C(O)NH2, —N(R3)2, —N(R3)S(O)2R3, —N(R3)S(O)2OR3, or —N(R3)S(O)2N(R3)2, wherein each R3 is independently hydrogen, C1-C6alkyl, C3-6cycloalkyl, or C1-C6haloalkyl.

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LXR modulators

Life of this patent

LXR modulators

Life of this patent

Abstract

Claims19