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US 2017/0247366 A1Published application
Substituted 4-alkoxypicolinamide analogs as mglur5 negative allosteric modulators and methods of making and using the same
OwnerKyle A. EMMITTE, Craig W. LINDSLEY +3inventors
InventorsKyle A. EMMITTE, Craig W. LINDSLEY, P. Jeffrey CONN, Andrew S. FELTS, Katrina A. Bollinger
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Abstract
Disclosed are negative allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
Claims20
A compound having a structure represented by a formula:
- wherein R1 is selected from hydrogen, C1-C4 alkyl, C1-C4 monohaloalkyl, C1-C4 polyhaloalkyl, and Cy1;
- wherein Cy1, when present, is selected from C3-C4 cycloalkyl substituted with 0, 1, 2, or 3 fluoro groups;
- wherein R2 is selected from C1-C8 alkoxyalkyl, —CR20aR20bCy2, and Cy2 and substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, C1-C3 alkyl, C1-C3 monohaloalkyl, C1-C3 polyhaloalkyl, —OR21, and —SO2R22;
- wherein each of R20a and R20b, when present, is independently selected from hydrogen, fluorine, C1-C3 alkyl, C1-C3 monohaloalkyl, and C1-C3 polyhaloalkyl;
- wherein each of R21 and R22, when present, is independently selected from hydrogen, C1-C3 alkyl, C1-C3 monohaloalkyl, and C1-C3 polyhaloalkyl;
- wherein Cy2, when present, is selected from:
- wherein each n and m, when present, is an integer independently selected from 1, 2, and 3;
- wherein each L, when present, is CH2 when R2 is Cy2;
- or, wherein each L, when present, is independently selected from O, S, S(O), SO2, and CH2 when R2 is —CR20aR20bCy2;
- wherein each Q, when present, is independently selected from O, S, S(O), SO2, and CH2;
- wherein each Z, when present, is independently selected from O, S, S(O), SO2, and CH2;
- wherein R30, when present, is selected from hydrogen and methyl;
- wherein R31, when present, is selected from —COR40, —SO2R41, —CO2R42, and —CONR43aR43b;
- wherein each of R40, R41, and R42, when present, is independently selected from C1-C6 alkyl, C1-C6 alkoxyalkyl, and Cy3 and substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, methyl, —CH2F, —CHF2, —CF3, —OCH3, —OCHF2, and —OCF3;
- wherein Cy3, when present, is selected from C3-C6 cycloalkyl and C3-C5 heterocycloalkyl and substituted with 0, 1, 2, or 3 fluoro groups;
- wherein each of R43a and R43b, when present, is independently selected from C1-C3 alkyl and C1-C3 alkoxyalkyl and substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, methyl, —CH2F, —CHF2, —CF3, —OCH3, —OCHF2, and —OCF3;
- or, wherein each of R43a and R43b are covalently bonded, and together with the intermediate atoms, comprise an optionally substituted 4- to 6-membered ring group;
- wherein Ar1 is selected from phenyl and C2-C5 heteroaryl and substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —(C1-C4 alkyl)-CN, C1-C4 alkyl, C1-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C1-C4 monohaloalkyl, C1-C4 polyhaloalkyl, —O—(C1-C4 alkyl), —O—(C1-C4 monohaloalkyl), —O—(C1-C4 polyhaloalkyl), Cy4, and —O-Cy4, and wherein two of the substituents are optionally covalently bonded, and together with the intermediate atoms, comprise an optionally substituted 5- to 6-membered fused ring group;
- wherein Cy4, when present, is selected from C3-C4 cycloalkyl and substituted with 0, 1, 2, or 3 fluoro groups;
- or a pharmaceutically acceptable salt thereof.
17 more elements
Dependencies are inferred from the claim text.