Metabotropic glutamate receptor negative allosteric modulators (nams) and uses thereof
AssigneeSanford Burnham Prebys Medical Discovery Institute
InventorsNicholas David Peter COSFORD, Dhanya RAVEENDRA-PANICKAR, Douglas J. SHEFFLER, John Howard HUTCHINSON, Reto Andreas GADIENT
Life of this patent
Estimating the term…
Abstract
Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor negative allosteric modulators (NAMs), compositions comprising the compounds, and methods of using the compounds and compositions.
Claims41
A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof, having the structure of Formula (I):
- wherein:
- ring
- is thiazolyl, thiadiazolyl, or triazolyl;
- ring
- is an aryl ring or heteroaryl ring;
- R1 is —CO2H, —CN, —C(O)NHOH, —C(O)NHOMe, —C(O)NHSO2Me, —NHC(O)Me, —C(O)NHMe,
- each R2 is independently halogen, —OR5, unsubstituted C1-C6alkyl, or unsubstituted C1-C6 fluoroalkyl;
- each R3 is independently unsubstituted C1-C6alkyl, unsubstituted C1-C6fluoroalkyl, unsubstituted C3-C6cycloalkyl, or unsubstituted aryl;
- each R4 is independently halogen, —OR5, unsubstituted C1-C6alkyl, unsubstituted C1-C6fluoroalkyl, unsubstituted C3-C6cycloalkyl, or unsubstituted aryl;
- or two R4 taken together with the carbon atoms to which they are attached to form a unsubstituted C2-C8 heterocycloalkyl;
- each R5 is independently hydrogen, or unsubstituted C1-C6alkyl;
- n is 0, 1, 2, or 3;
- m is 0 or 1;
- and
- p is 0, 1, 2, or 3;
- and
- at least one pharmaceutically acceptable excipient.
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A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof, having the structure of Formula (II):
- wherein:
- ring
- is an aryl ring or heteroaryl ring;
- X is a bond, —O—, or —S—;
- R1 is —CO2H, —C(O)NHOH, —C(O)NHOMe, —C(O)NHSO2Me, —NHC(O)Me, —C(O)NHMe,
- each R2 is independently halogen, —OR5, NO2, unsubstituted C1-C6alkyl, or unsubstituted C1-C6 fluoroalkyl;
- each R3 is independently halogen, —OR5, —SR5, unsubstituted C1-C6alkyl, unsubstituted C1-C6fluoroalkyl, unsubstituted C3-C6cycloalkyl, or unsubstituted aryl;
- R4 is H, —CF3, —CH3, or unsubstituted phenyl;
- each R5 is independently hydrogen, or unsubstituted C1-C6 alkyl;
- n is 0, 1, 2, or 3;
- and
- m is 0, 1 or 2;
- and
- at least one pharmaceutically acceptable excipient.
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A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof, having the structure of Formula (III):
- wherein:
- Z is ═N— or ═C(H)—;
- R1 is halogen, —OR5, —NO2, —CN, unsubstituted C1-C6alkyl, unsubstituted C1-C6fluoroalkyl, unsubstituted aryl, unsubstituted heteroaryl, or —CO2R6;
- each R2 is independently halogen, —OR5, NO2, unsubstituted C1-C6alkyl, or unsubstituted C1-C6fluoroalkyl;
- R3 is —X—R4;
- X is —O—, —S—, —S(O)2—, —N(R7)—, or —C≡C—;
- R4 is unsubstituted C3-C6cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
- each R5 is independently hydrogen, or unsubstituted C1-C6alkyl;
- R6 is hydrogen, or unsubstituted C1-C6alkyl;
- R7 is hydrogen, or unsubstituted C1-C6alkyl;
- each R8 is independently halogen, or unsubstituted C1-C6alkyl;
- n is 1, 2, or 3;
- and
- m is 0, 1, or 2.
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Dependencies are inferred from the claim text.