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US 12,006,300 B2Granted
Sigma ligand compounds and uses thereof
AssigneeMinerva Neurosciences, Inc.
InventorsRemy Luthringer, Nadine Noel, Florent Schmitt, Sandra Werner, Hans Maag, Jay Saoud
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to compounds of Formula (I): and their prodrugs, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods of their preparation. The compounds disclosed herein are useful for modulating Sigma receptors and have antiviral activity, and may also be useful in the treatment and/or prevention of pain disorders, neurological disorders (e.g., Parkinson's disease and Alzheimer's disease), and cancer.
Claims41
A compound of Formula (I):
- or a solvate or pharmaceutically acceptable salt thereof, wherein
- X1 is absent, —(CR3R4)q—, —O—, —S(O)2—, —C(O)—, —C(S)—, —S(O)—, —NR3C(O)—, —C(O)NR3—, —C(O)O—, or —OC(O)—;
- X2 is absent, —(CR3R4)q—, —O—, —S(O2)—, —C(O)—, —C(S)—, —S(O)—, —NR3C(O)—, —C(O)NR3—, —C(O)O—, or —OC(O)—;
- R1 is H, OH, halogen, NH2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxyl, C1-C6 haloalkoxyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 12-membered heteroaryl comprising 1-6 heteroatoms selected from N, O, and S, 5- to 14-membered saturated or unsaturated heterocycloalkyl comprising 1-5 heteroatoms selected from N, O, and S;
- wherein the alkyl, alkenyl, alkynyl, haloalkyl, alkoxyl, haloalkoxyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl of any of the foregoing is optionally substituted with one or more R5;
- R2 is C6-C10 aryl, 5- to 12-membered heteroaryl comprising 1-6 heteroatoms selected from N, O, and S, or 5- to 14-membered saturated or unsaturated heterocycloalkyl comprising 1-5 heteroatoms selected from N, O, and S;
- wherein the aryl, heteroaryl, or heterocycloalkyl of any of the foregoing is optionally substituted with one or more R6;
- each R3 independently is H, halogen, or C1-C6 alkyl;
- each R4 independently is H, halogen, or C1-C6 alkyl;
- each R5 independently is OH, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxyl, C1-C6 haloalkoxyl, C3-C6 cycloalkyl, C6-C10 aryl, or 5- to 14-membered saturated or unsaturated heterocycloalkyl comprising 1-5 heteroatoms selected from N, O, and S;
- wherein the alkyl, alkenyl, alkynyl, cycloalkyl, or aryl of any of the foregoing is optionally substituted with one or more —C(O)C1-C6alkyl, —C(O)OC1-C6alkyl, —C(O)NH2, —C(O)NHC1-C6alkyl, or —C(O)N(C1-C6alkyl)2;
- each R6 independently is OH, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxyl, C1-C6 haloalkoxyl, C3-C6 cycloalkyl, C6-C10 aryl, or 5- to 14-membered saturated or unsaturated heterocycloalkyl comprising 1-5 heteroatoms selected from N, O, and S;
- wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or heterocycloalkyl of any of the foregoing is optionally substituted with one or more —C(O)C1-C6 alkyl, —C(O)OC1-C6 alkyl, —C(O)NH2, —C(O)NHC1-C6 alkyl, or —C(O)N(C1-C6alkyl)2;
- R7 is C1-C6 alkyl optionally substituted with one or more OH, halogen, or C1-C6 alkoxyl;
- R8 is C1-C6 alkyl optionally substituted with one or more OH, halogen, or C1-C6 alkoxyl;
- m is 1;
- n is 2;
- p is 1;
- and
- each q independently is 1, 2, 3, or 4.
17 more elements
A compound that is:
- or a solvate or pharmaceutically acceptable salt thereof.
A compound of Formula (I):
- or a solvate or pharmaceutically acceptable salt thereof, wherein
- X1 is absent, —(CR3R4)q—, —O—, —S(O)2—, —C(O)—, —C(S)—, —S(O)—, —NR3C(O)—, —C(O)NR3—, —C(O)O—, or —OC(O)—;
- X2 is absent, —(CR3R4)q—, —O—, —S(O2)—, —C(O)—, —C(S)—, —S(O)—, —NR3C(O)—, —C(O)NR3—, —C(O)O—, or —OC(O)—;
- R1 is H, OH, halogen, NH2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxyl, C1-C6 haloalkoxyl, C3-C6 cycloalkyl, C6-C10 aryl, 5- to 12-membered heteroaryl comprising 1-6 heteroatoms selected from N, O, and S, 5- to 14-membered saturated or unsaturated heterocycloalkyl comprising 1-5 heteroatoms selected from N, O, and S;
- wherein the alkyl, alkenyl, alkynyl, haloalkyl, alkoxyl, haloalkoxyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl of any of the foregoing is optionally substituted with one or more R5;
- R2 is
- each R3 independently is H, halogen, or C1-C6 alkyl;
- each R4 independently is H, halogen, or C1-C6 alkyl;
- each R5 independently is OH, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxyl, C1-C6 haloalkoxyl, C3-C6 cycloalkyl, C6-C10 aryl, or 5- to 14-membered saturated or unsaturated heterocycloalkyl comprising 1-5 heteroatoms selected from N, O, and S;
- wherein the alkyl, alkenyl, alkynyl, cycloalkyl, or aryl of any of the foregoing is optionally substituted with one or more —C(O)C1-C6alkyl, —C(O)OC1-C6alkyl, —C(O)NH2, —C(O)NHC1-C6alkyl, or —C(O)N(C1-C6alkyl)2;
- R7 is C1-C6 alkyl optionally substituted with one or more OH, halogen, or C1-C6 alkoxyl;
- R8 is C1-C6 alkyl optionally substituted with one or more OH, halogen, or C1-C6 alkoxyl;
- and
- each q independently is 1, 2, 3, or 4.
11 more elements
The compound of 28, wherein R1 is H, OH, or halogen.
Dependencies are inferred from the claim text.