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US 7,247,748 B2Granted
Amide compounds and methods of using the same
AssigneeSmithKline Corporation
InventorsScott K. Thompson, James S. Frazee, Lara S. Kallander, Chun Ma, Joseph P. Marino, Michael J. Neeb, Ning Wang
Life of this patent
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Abstract
Disclosed is a compound having the formula (I) pharmaceutically acceptable salts or solvates thereof and pharmaceutical compositions containing the same, wherein the structural variables are as defined herein. The compounds, salts and solvates of this invention are useful as LXR agonists
Claims27
A compound of Formula I:
- wherein:
- Z is CH, CR3 or N, wherein when Z is CH or CR3, k is 0–4 and t is 0 or 1, and when Z is N, k is 0–3 and t is 0;
- Y is selected from —O—, —S—, —N(R12)—, and —C(R4)(R5)—;
- W1 is selected from C1–C6 alkyl, C0–C6 alkyl C3–C8 cycloalkyl, aryl and Het, wherein said C1–C8 alkyl, C3–C8 cycloalkyl, Ar and Het are optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, C1–C6 alkyl, C3–C6 alkenyl, C3–C6 alkynyl, —C0–C6 alkyl-CO2R12, —C0–C6 alkyl-C(O)SR12, —C0–C6 alkyl-CONR13R14, —C0–C6 alkyl-COR15, —C0–C6 alkyl-NR13R14, —C0–C6 alkyl-SR12, —C0–C6 alkyl-OR12, —C0–C6 alkyl-SO3H, —C0–C6 alkyl-SO2NR13R14, —C0–C6 alkyl-SO2R12, —C0–C6 alkyl-SOR15, —C0–C6 alkyl-OCOR15, —C0–C6 alkyl-OC(O)NR13R14, —C0–C6 alkyl-OC(O)OR15, —C0–C6 alkyl-NR13C(O)OR15, —C0–C6 alkyl-NR13C(O)NR13R14, and —C0–C6 alkyl-NR13COR15, where said C1–C6 alkyl, is optionally unsubstituted or substituted by one or more halo substituents;
- W2 is selected from H, halo, C1–C6 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, —C0–C6 alkyl-NR13R14, —C0–C6 alkyl-SR12, —C0–C6 alkyl-OR12, —C0–C6 alkyl-CO2R12, —C0–C6 alkyl-C(O)SR12, —C0–C6 alkyl-CONR13R14, —C0–C6 alkyl-COR15, —C0–C6 alkyl-OCOR15, —C0–C6 alkyl-OCONR13R14, —C0–C6 alkyl-NR13CONR13R14, —C0–C6 alkyl-NR13COR15, —C0–C6 alkyl-Het, —C0–C6 alkyl-Ar and —C0–C6 alkyl-C3–C7 cycloalkyl, wherein said C1–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, C1–C6 alkyl, C3–C6 alkenyl, C3–C6 alkynyl, —C0–C6 alkyl-CO2R12, —C0–C6 alkyl-C(O)SR12, —C0–C6 alkyl-CONR13R14, —C0–C6 alkyl-COR15, —C0–C6 alkyl-NR13R14, —C0–C6 alkyl-SR12, —C0–C6 alkyl-OR12, —C0–C6 alkyl-SO3H, —C0–C6 alkyl-SO2NR13R14, —C0–C6 alkyl-SO2R12, —C0–C6 alkyl-SOR15, —C0–C6 alkyl-OCOR15, —C0–C6 alkyl-OC(O)NR13R14, —C0–C6 alkyl-OC(O)OR15, —C0–C6 alkyl-NR13C(O)OR15, —C0–C6 alkyl-NR13C(O)NR13R14, and —C0–C6 alkyl-NR13COR15, where said C1–C6 alkyl, is optionally unsubstituted or substituted by one or more halo substituents;
- W3 is selected from the group consisting of:
- H, halo, C1–C6 alkyl, —C0–C6 alkyl-NR13R14, —C0–C6 alkyl-SR12, —C0–C6 alkyl-OR12, —C0–C6 alkyl-CO2R12, —C0–C6 alkyl-C(O)SR12, —C0–C6 alkyl-CONR13R14, —C0–C6 alkyl-COR15, —C0–C6 alkyl-OCOR15, —C0–C6 alkyl-OCONR13R14, —C0–C6 alkyl-NR13CONR13R14, —C0–C6 alkyl-NR13COR15, —C0–C6 alkyl-Het, —C1–C6 alkyl-Ar and —C1–C6 alkyl-C3–C7 cycloalkyl, wherein said C1–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, C1–C6 alkyl, C3–C6 alkenyl, C3–C6 alkynyl, —C0–C6 alkyl-CO2R12, —C0–C6 alkyl-C(O)SR12, —C0–C6 alkyl-CONR13R14, —C0–C6 alkyl-COR15, —C0–C6 alkyl-NR13R14, —C0–C6 alkyl-SR12, —C0–C6 alkyl-OR12, —C0–C6 alkyl-SO3H, —C0–C6 alkyl-SO2NR13R14, —C0–C6 alkyl-SO2R12, —C0–C6 alkyl-SOR15, —C0–C6 alkyl-OCOR15, —C0–C6 alkyl-OC(O)NR13R14, —C0–C6 alkyl-OC(O)OR15, —C0–C6 alkyl-NR13C(O)OR15, —C0–C6 alkyl-NR13C(O)NR13R14, and —C0–C6 alkyl-NR13COR15, where said C1–C6 alkyl is optionally unsubstituted or substituted by one or more halo substituents;
- p is 0–8;
- n is 2–8;
- m is 0 or 1;
- q is 0 or 1;
- t is 0 or 1;
- each R1 and R2 are independently selected from H, halo, C1–C6 alkyl, C3–C6 alkenyl, C3–C6 alkynyl, —C0–C6 alkyl-NR13R14, —C0–C6 alkyl-OR12, —C0–C6 alkyl-SR12, —C1–C6 alkyl-Het, —C1–C6 alkyl-Ar and —C1–C6 alkyl-C3–C7 cycloalkyl, or R1 and R2 together with the carbon to which they are attached form a 3–5 membered carbocyclic or heterocyclic ring, wherein said heterocyclic ring contains one, or more heteroatoms selected from N, O, and S, where any of said C1–C6 alkyl is optionally unsubstituted or substituted by one or more halo substituents;
- each R3 is the same or different and is independently selected from halo, cyano, nitro, C1–C6 alkyl, C3–C6 alkenyl, C3–C6 alkynyl, —C0–C6 alkyl-Ar, —C0–C6 alkyl-Het, —C0–C6 alkyl-C3–C7 cycloalkyl, —C0–C6 alkyl-CO2R12, —C0–C6 alkyl-C(O)SR12, —C0–C6 alkyl-CONR13R14, —C0–C6 alkyl-COR15, —C0–C6 alkyl-NR13R14, —C0–C6 alkyl-SR12, —C0–C6 alkyl-OR12, —C0–C6 alkyl-SO3H, —C0–C6 alkyl-SO2NR13R14, —C0–C6 alkyl-SO2R12, —C0–C6 alkyl-SOR15, —C0–C6 alkyl-OCOR15, —C0–C6 alkyl-OC(O)NR13R14, —C0–C6 alkyl-OC(O)OR15, —C0–C6 alkyl-NR13C(O)OR15, —C0–C6 alkyl-NR13C(O)NR13R14, and —C0–C6 alkyl-NR13COR15, wherein said C1–C6 alkyl is optionally unsubstituted or substituted by one or more halo substituents;
- each R4 and R5 is independently selected from H, halo, C1–C6 alkyl, —C0–C6 alkyl-Het, —C0–C6 alkyl-Ar and —C0–C6 alkyl-C3–C7 cycloalkyl;
- R6 and R7 are each independently selected from H, halo, C1–C6 alkyl, —C0–C6 alkyl-Het, —C0–C6 alkyl-Ar and —C0–C6 alkyl-C3–C7 cycloalkyl;
- R8 and R9 are each independently selected from H, halo, C1–C6 alkyl, —C0–C6 alkyl-Het, —C0–C6 alkyl-Ar and —C0–C6 alkyl-C3–C7 cycloalkyl;
- R10 and R11 are each independently selected from H, C1–C12 alkyl, C3–C12 alkenyl, C3–C12 alkynyl, —C0–C8 alkyl-Ar, —C0–C8 alkyl-Het, —C0–C8 alkyl-C3–C7 cycloalkyl, —C0–C8 alkyl-O-Ar, —C0–C8 alkyl-O-Het, —C0–C8 alkyl-O—C3–C7 cycloalkyl, —C0–C8 alkyl-S(O)x—C0–C6 alkyl, —C0–C8 alkyl-S(O)x-Ar, —C0–C8 alkyl-S(O)x-Het, —C0–C8 alkyl-S(O)x—C3–C7 cycloalkyl, —C0–C8 alkyl-NH-Ar, —C0–C8 alkyl-NH-Het, —C0–C8 alkyl-NH—C3–C7 cycloalkyl, —C0–C8 alkyl-N(C1–C4 alkyl)-Ar, —C0–C8 alkyl-N(C1–C4 alkyl)-Het, —C0–C8 alkyl-N(C1–C4 alkyl)-C3–C7 cycloalkyl, —C0–C8 alkyl-Ar, —C0–C8 alkyl-Het and —C0–C8 alkyl-C3–C7 cycloalkyl, where x is 0, 1 or 2, or R10 and R11, 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 C1–C12 alkyl, C3–C12 alkenyl, or C3–C12 alkynyl is optionally substituted by one or more of the substituents independently selected from the group halo, —OH, —SH, —NH2, —NH(unsubstituted C1–C6 alkyl), —N(unsubstituted C1–C6 alkyl)(unsubstituted C1–C6 alkyl), unsubstituted —OC1–C6 alkyl, —CO2H, —CO2(unsubstituted C1–C6 alkyl), —CONH2, —CONH(unsubstituted C1–C6 alkyl), —CON(unsubstituted C1–C6 alkyl)(unsubstituted C1–C6 alkyl), —SO3H, —SO2NH2, —SO2NH(unsubstituted C1–C6 alkyl) and —SO2N(unsubstituted C1–C6 alkyl)(unsubstituted C1–C6 alkyl);
- R12 is selected from H, C1–C6 alkyl, C3–C6 alkenyl, C3–C6 alkynyl, —C0–C6 alkyl-Ar, —C0–C6 alkyl-Het and —C0–C6 alkyl-C3–C7 cycloalkyl;
- each R13 and each R14 are independently selected from H, C1–C6 alkyl, C3–C6 alkenyl, C3–C6 alkynyl, —C0–C6 alkyl-Ar, —C0–C6 alkyl-Het and —C0–C6 alkyl-C3–C7 cycloalkyl, or R13 and R14 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;
- and
- R15 is selected from C1–C6 alkyl, C3–C6 alkenyl, C3–C6 alkynyl, —C0–C6 alkyl-Ar, —C0–C6 alkyl-Het and —C0–C6 alkyl-C3–C7 cycloalkyl;
- provided that R10 and R11 are not both H when Z is CH or N, Y is —O—, n is 3, m is 1 and each R4, R5, R6, R7 are H, W3 is H, p is 0 or p is 1 or 2 and R1 and R2 are each H, k is 0 or k is 1 and R3 is halo or C1–C4 alkoxy, q is 0 or q is 1 or 2 and R8 and R9 are each H, Q is unsubstituted C3–C7 cycloalkyl, phenyl or Het, or phenyl substituted by one or more substituents selected from halo, —CH3, —CH2CH3, —CF3, —OC1–C4 alkyl, —OCH2CH2OH, —OCF3, —OCF2H, —SCH3, —SCF3, —SO2CH3, —CO2H, —CO2CH3, —OH, —OCH2CO2H, —CH2CONH2, —NO2, —CN, —N(CH3)2, and —NHC(O)CH3, or Het substituted by one or more substituents selected from:
- —C1–C3 alkyl, —OC1–C4 alkyl, —CH2OH, —CO2H, —CO2CH2CH3, —CO2-tert-C4H9 alkyl, —CO2CH2-phenyl, —CONH2, —C(O)phenyl, —C(O)CH3, —CH2CH2-phenyl, and oxo, t is 0, and W1 and W2 are each independently selected from unsubstituted cyclohexyl and unsubstituted phenyl;
- or
- provided that the compound is not:
- 3-[3-[[2-[3,4-bis(phenylmethoxy)phenyl]-2-hydroxyethyl](phenylmethyl)amino]propyl]-benzamide,
- (S)-2-hydroxy-5-[2-[(2-hydroxy-2-phenylethyl)(phenylmethyl)amino]ethoxy]-benzamide,
- 5-[2-[[2-[3,5-bis(phenylmethoxy)phenyl]-2-hydroxyethyl](phenylmethyl)amino]ethoxy]-2-hydroxy-benzamide,
- 2-hydroxy-4-[3-[(2-hydroxy-2-phenylethyl)(phenylmethyl)amino]propoxy]-benzamide,
- 2-hydroxy-4-[2-[(2-hydroxy-2-phenylethyl)(phenylmethyl)amino]ethoxy]-benzamide,
- (R)-2-hydroxy-5-[2-[(2-hydroxy-2-phenylethyl)(phenylmethyl)amino]ethoxy]-benzamide,
- 2-hydroxy-5-[3-[(2-hydroxy-2-phenylethyl)(phenylmethyl)amino]propyl]-benzamide,
- 2-hydroxy-5-[2-[(2-hydroxy-2-phenylethyl)(phenylmethyl)amino]ethoxy]-benzamide,
- 5-[2-[[2-(4-fluorophenyl)-2-hydroxyethyl](phenylmethyl)amino]ethoxy]-2-hydroxy-benzamide,
- 5-[2-[[2-[3-(aminosulfonyl)-4-methoxyphenyl]-2-hydroxyethyl](phenylmethyl)amino]ethoxy]-2-hydroxy-benzamide,
- (R)-4-[2-[[2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethyl](phenylmethyl)amino]ethoxy]-benzeneacetamide,
- (R)-4-[2-[(2-hydroxy-2-phenylethyl)(phenylmethyl)amino]ethoxy]-benzeneacetamide,
- 4-[2-[(2-hydroxy-2-phenylethyl)(phenylmethyl)amino]ethoxy]-benzeneacetamide,
- 5-[2-[[2-(4-fluorophenyl)-2-hydroxyethyl](phenylmethyl)amino]ethoxy]-2-hydroxy-benzamine, or
- 4-[2-[[2-[3,4-bis(phenylmethoxy)phenyl]-2-hydroxyethyl](phenylmethyl)amino]ethoxy]-benzamide,
- or a pharmaceutically acceptable salt or solvate thereof.
41 more elements
A compound having Formula II:
- wherein:
- Z is CH or N, wherein k is 0, 1 or 2;
- Y is —O— or —C(R4)(R5)—;
- W1 is selected from C1–C6 alkyl, C3–C8 cycloalkyl, aryl or Het, wherein said C1–C6 alkyl, C3–C8 cycloalkyl, Ar and Het are optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, C1–C6 alkyl, C3–C6 alkenyl, C3–C6 alkynyl, —C0–C4 alkyl-CO2R12, —C0–C4 alkyl-C(O)SR12, —C0–C4 alkyl-CONR13R14, —C0–C4 alkyl-COR15, —C0–C4 alkyl-NR13R14, —C0–C4 alkyl-SR12, —C0–C4 alkyl-OR12, —C0–C4 alkyl-SO3H, —C0–C4 alkyl-SO2NR13R14, —C0–C4 alkyl-SO2R12, —C0–C4 alkyl-SOR15, —C0–C4 alkyl-OCOR15, —C0–C4 alkyl-OC(O)NR13R14, —C0–C4 alkyl-OC(O)OR15, —C0–C4 alkyl-NR13C(O)OR15, —C0–C4 alkyl-NR13C(O)NR13R14, and —C0–C4 alkyl-NR13COR15, where said C1–C6 alkyl is optionally unsubstituted or substituted by one or more halo substituents;
- W2 is selected from H, halo, C1–C6 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, —C0–C4 alkyl-NR13R14, —C0–C4 alkyl-SR12, —C0–C4 alkyl-OR12, —C0–C4 alkyl-CO2R12, —C0–C4 alkyl-C(O)SR12, —C0–C4 alkyl-CONR13R14, —C0–C4 alkyl-COR15, —C0–C4 alkyl-OCOR15, —C0–C4 alkyl-OCONR13R14, —C0–C4 alkyl-NR13CONR13R14, —C0–C4 alkyl-NR13COR15, —C0–C4 alkyl-Het, —C0–C4 alkyl-Ar and —C0–C4 alkyl-C3–C7 cycloalkyl, wherein said C1–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–C4 alkyl-Het, —C0–C4 alkyl-Ar and —C0–C4 alkyl-C3–C7 cycloalkyl are optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, C1–C6 alkyl, C3–C6 alkenyl, C3–C6 alkynyl, —C0–C4 alkyl-CO2R12, —C0–C4 alkyl-C(O)SR12, —C0–C4 alkyl-CONR13R14, —C0–C4 alkyl-COR15, —C0–C4 alkyl-NR13R14, —C0–C4 alkyl-SR12, —C0–C4 alkyl-OR12, —C0–C4 alkyl-SO3H, —C0–C4 alkyl-SO2NR13R14, —C0–C4 alkyl-SO2R12, —C0–C4 alkyl-SOR15, —C0–C4 alkyl-OCOR15, —C0–C4 alkyl-OC(O)NR13R14, —C0–C4 alkyl-OC(O)OR15, —C0–C4 alkyl-NR13C(O)OR15, —C0–C4 alkyl-NR13C(O)NR13R14, and —C0–C4 alkyl-NR13COR15, where said C1–C6 alkyl, is optionally unsubstituted or substituted by one or more halo substituents;
- W3 is selected from the group consisting of:
- H, halo, C1–C6 alkyl, —C0–C4 alkyl-NR13R14, —C0–C4 alkyl-SR12, —C0–C4 alkyl-OR12, —C0–C4 alkyl-CO2R12, —C0–C4 alkyl-C(O)SR12, —C0–C4 alkyl-CONR13R14, —C0–C4 alkyl-COR15, —C0–C4 alkyl-OCOR15, —C0–C4 alkyl-OCONR13R14, —C0–C4 alkyl-NR13CONR13R14, —C0–C4 alkyl-NR13COR15, —C0–C4 alkyl-Het, —C1–C4 alkyl-Ar and —C1–C4 alkyl-C3–C7 cycloalkyl, wherein said C1–C6 alkyl is optionally unsubstituted or substituted by one or more halo substituents;
- Q is phenyl or Het;
- wherein said phenyl or Het are optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, C1–C6 alkyl, C3–C6 alkenyl, C3–C6 alkynyl, —C0–C4 alkyl-CO2R12, —C0–C4 alkyl-C(O)SR12, —C0–C4 alkyl-CONR13R14, —C0–C4 alkyl-COR15, —C0–C4 alkyl-NR13R14, —C0–C4 alkyl-SR12, —C0–C4 alkyl-OR12, —C0–C4 alkyl-SO3H, —C0–C4 alkyl-SO2NR13R14, —C0–C4 alkyl-SO2R12, —C0–C4 alkyl-SOR15, —C0–C4 alkyl-OCOR15, —C0–C4 alkyl-OC(O)NR13R14, —C0–C4 alkyl-OC(O)OR15, —C0–C4 alkyl-NR13C(O)OR15, —C0–C4 alkyl-NR13C(O)NR13R14, and —C0–C4 alkyl-NR13COR15, where said C1–C6 alkyl is optionally unsubstituted or substituted by one or more halo substituents,
- p is 0–4;
- n is 3;
- m is 0 or 1;
- q is 0 or 1;
- t is 0;
- each R1 and R2 are independently selected from H, fluoro, C1–C6 alkyl, —C0–C4 alkyl-OR12, —C0–C4 alkyl-SR12, —C1–C4 alkyl-Het, —C1–C4 alkyl-Ar and —C1–C4 alkyl-C3–C7 cycloalkyl, where any of said C1–C6 alkyl is optionally unsubstituted or substituted by one or more halo substituents;
- each R3 is the same or different and is independently selected from halo, cyano, C1–C6 alkyl, —C0–C4 alkyl-NR13R14, —C0–C4 alkyl-OR12, —C0–C4 alkyl-SO2NR13R14, and —C0–C4 alkyl-CO2H, wherein said C1–C6 alkyl is optionally unsubstituted or substituted by one or more halo substituents;
- each R4 and R5 is independently selected from H, fluoro and C1–C6 alkyl;
- R6 and R7 are each independently selected from H, fluoro and C1–C6 alkyl;
- R8 and R9 are each independently selected from H, fluoro and C1–C6 alkyl;
- R10 and R11 are each independently selected from H, C1–C10 alkyl, C3–C8 alkenyl, C3–C8 alkynyl, —C0–C6 alkyl-Ar, —C0–C6 alkyl-Het, —C0–C6 alkyl-C3–C7 cycloalkyl, —C0–C6 alkyl-O-Ar, —C0–C6 alkyl-O-Het, —C0–C6 alkyl-O—C3–C7 cycloalkyl, —C0–C6 alkyl-S(O)x—C1–C6 alkyl, —C0–C6 alkyl-S(O)x-Ar, —C0–C6 alkyl-S(O)x-Het, —C0–C6 alkyl-S(O)x—C3–C7 cycloalkyl, —C0–C6 alkyl-NH-Ar, —C0–C6 alkyl-NH-Het, —C0–C6 alkyl-NH—C3–C7 cycloalkyl, —C0–C6 alkyl-N(C1–C4 alkyl)-Ar, —C0–C6 alkyl-N(C1–C4 alkyl)-Het, —C0–C6 alkyl-N(C1–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 R11 and R12, 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 C1–C10 alkyl, C3–C10 alkenyl, C3–C10 alkynyl are optionally substituted by one or more of the substituents independently selected from the group halo, —OH, —SH, —NH2, —NH(unsubstituted C1–C4 alkyl), —N(unsubstituted C1–C4 alkyl)(unsubstituted C1–C4 alkyl), unsubstituted —OC1–C4 alkyl, —CO2H, —CO2(unsubstituted C1–C4 alkyl), —CONH2, —CONH(unsubstituted C1–C4 alkyl), —CON(unsubstituted C1–C4 alkyl)(unsubstituted C1–C4 alkyl), —SO3H, —SO2NH2, —SO2NH(unsubstituted C1–C4 alkyl) and —SO2N(unsubstituted C1–C4 alkyl)(unsubstituted C1–C4 alkyl);
- R12 is selected from H, C1–C6 alkyl, —C0–C4 alkyl-Ar, —C0–C4 alkyl-Het and —C0–C4 alkyl-C3–C7 cycloalkyl;
- each R13 and R14 are each independently selected from H, C1–C6 alkyl, —C0–C4 alkyl-Ar, —C0–C4 alkyl-Het and —C0–C4 alkyl-C3–C7 cycloalkyl, or R13 and R14 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;
- and
- R15 is selected from C1–C6 alkyl, —C0–C4 alkyl-Ar, —C0–C4 alkyl-Het and —C0–C4 alkyl-C3–C7 cycloalkyl;
- provided that R10 and R11 are not both H when Z is CH or N, Y is —O—, n is 3, m is 1 and each R4, R5, R6, R7 are H, W3 is H, p is 0 or p is 1 or 2 and R1 and R2 are each H, k is 0 or k is 1 and R3 is halo or C1–C4 alkoxy, q is 0 or q is 1 or 2 and R8 and R9 are each H, Q is unsubstituted phenyl or Het, or phenyl substituted by one or more substituents selected from halo, —CH3, —CH2CH3, —CF3, —OC1–C4 alkyl, —OCH2CH2OH, —OCF3, —OCF2H, —SCH3, —SCF3, —SO2CH3, —CO2H, —CO2CH3, —OH, —OCH2CO2H, —CH2CONH2, —NO2, —CN, —N(CH3)2, and —NHC(O)CH3, or Het substituted by one or more substituents selected from:
- —C1–C3 alkyl, —OC1–C4 alkyl, —CH2OH, —CO2H, —CO2CH2CH3, —CO2-tert-C4H9 alkyl, —CO2CH2-phenyl, —CONH2, —C(O)phenyl, —C(O)CH3, —CH2CH2-phenyl, and oxo, t is 0, and W1 and W2 are each independently selected from unsubstituted cyclohexyl and unsubstituted phenyl;
- or
- provided that the compound is not 2-hydroxy-4-[3-[(2-hydroxy-2-phenylethyl)(phenylmethyl)amino]propoxy]-benzamide,
- or a pharmaceutically acceptable salt or solvate thereof.
26 more elements
A compound selected from:
- 2-(3-{3-[(2-chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-propoxy}phenyl)-1-morpholin-4-yl-ethanone;
- 2-(3-{3-[(2-chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-propoxy}phenyl)-N-methyl-acetamide;
- 2-(3-{3-[(2-chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-propoxy}phenyl)-N,N-dimethyl-acetamide;
- 2-(3-{3-[(2-chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-propoxy}phenyl)-1-piperidyn-1-yl-ethanone;
- 2-(3-{3-[(2-chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-propoxy}phenyl)-1-(4-methyl-piperazin-1-yl)-ethanone;
- 2-(3-{3-[(2-chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-propoxy}phenyl)-1-pyrrolidin-1-yl-ethanone;
- 2-(3-{3-[(2-chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-propoxy}phenyl)-N-ethyl-acetamide;
- 2-(3-{3-[(2-chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-propoxy}phenyl)-N,N-diethyl-acetamide;
- 2-(3-{3-[(2-chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-propoxy}phenyl)-1-azetidin-1-yl-ethanone;
- 2-(3-{3-[(2-chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-propoxy}phenyl)-1-azepan-1-yl-ethanone;
- (S)-2-(3-{3-[[2-chloro-3-(trifluoromethyl)benzyl](2-phenyl-propyl)amino]propoxy}-phenyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(1H-imidazol-2-ylmethyl)-acetamide;
- N-(5-bromo-thiophen-2-ylmethyl)-2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-thiophen-2-ylmethyl-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(2-methoxy-ethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(2-dimethylamino-ethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(2-morpholin-4-yl-ethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(2-methoxy-1-methyl-ethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(2-methoxy-ethyl)-N-methyl-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N,N-bis-(2-methoxy-ethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-furan-2-ylmethyl-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(3-methyl-isoxazol-5-ylmethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(2-thiomorpholin-4-yl-ethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(2-pyrrolidin-1-yl-ethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-pyridin-3-ylmethyl-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(2-pyridin-2-yl-ethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(3-phenoxy-ethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(3-isopropoxy-propyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(3-methoxy-propyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(5-methyl-[1,3,4] oxadiazol-2-ylmethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(4-methyl-thiazol-2-ylmethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(1-thiophen-2-yl-ethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-thiophen-3-ylmethyl-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(5-methyl-4H-[1,2,4]triazol-3-ylmethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-pyridin-2-ylmethyl-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(tetrahydro-furan-2-ylmethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-(1-ethyl-pyrrolidin-2-ylmethyl)-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-octyl-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-decyl-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-[2-(2-hydroxy-ethoxy)-ethyl]-acetamide;
- [2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-ethanoylamino]-2-thiophen-2-yl-acetic acid;
- 3-[2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-ethanoylamino]-propionic acid;
- 3-[2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-ethanoylamino]-acetic acid;
- (R)-2-(3-{3-[(2-chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-2-methyl-propoxy}phenyl)-1-morpholin-4-yl-ethanone;
- 2-(3-{(R)-3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-butoxy}-phenyl)-1-morpholin-4-yl-ethanone;
- 4-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-N,N-dimethyl-benzamide;
- 1-(4-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-1-morpholin-4-yl-methanone;
- 1-(4-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-1-(4-methyl-piperazin-1-yl)-methanone;
- 3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-N,N-dimethyl-benzamide;
- 3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-N-phenyl-benzamide;
- 1-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-1-morpholin-4-yl-methanone;
- 1-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-1-(4-methyl-piperazin-1-yl)-methanone;
- N-[1-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-methanoyl]-methanesulfonamide;
- N-[1-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-methanoyl]-benzenesulfonamide;
- N-[2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-ethanoyl]-methanesulfonamide;
- N-[2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-ethanoyl]-benzenesulfonamide
- N-[-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl-ethanoyl]-N-methyl-benzenesulfonamide;
- N-[2-(3-{3-[(chlorotrifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-ethanoyl]-N-methyl-methanesulfonamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-((S)-2-phenyl-propyl)-amino]-propoxy}-phenyl)-1-morpholin-4-yl-ethanone;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-((S)-2-phenyl-propyl)-amino]-propoxy}-phenyl)-N-ethyl-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-((R)-2-phenyl-propyl)-amino]-propoxy}-phenyl)-N,N-dimethyl-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-((R)-2-phenyl-propyl)-amino]-propoxy}-phenyl)acetamide;
- 2-(3-{3-[(2-cChloro-3-trifluoromethyl-benzyl)-((R)-2-phenyl-propyl)-amino]-propoxy}-phenyl)-N-methyl-acetamide;
- 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-((R)-2-phenyl-propyl)-amino]-propoxy}-phenyl)-N,N-dimethyl-acetamide,
- and a stereoisomer, a stereoisomeric mixture or racemate thereof and a pharmaceutically acceptable salt or solvate thereof.
62 more elements
Dependencies are inferred from the claim text.