US 12,006,300 B2
Sigma ligand compounds and uses thereof
Remy Luthringer, Geneva (CH); Nadine Noel, Gildwiller (FR); Florent Schmitt, Uttenheim (FR); Sandra Werner, Ostwald (FR); Hans Maag, Oberammergau (DE); and Jay Saoud, Groton, MA (US)
Assigned to Minerva Neurosciences, Inc., Burlington, MA (US)
Filed by Minerva Neurosciences, Inc., Waltham, MA (US)
Filed on Aug. 12, 2021, as Appl. No. 17/400,207.
Claims priority of provisional application 63/066,064, filed on Aug. 14, 2020.
Prior Publication US 2023/0054070 A1, Feb. 23, 2023
Int. Cl. C07D 401/04 (2006.01); C07D 217/06 (2006.01); C07D 217/08 (2006.01); C07D 223/16 (2006.01); C07D 401/06 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 403/04 (2006.01); C07D 403/10 (2006.01); C07D 405/06 (2006.01); C07D 405/12 (2006.01); C07D 405/14 (2006.01); C07D 417/06 (2006.01)
CPC C07D 401/04 (2013.01) [C07D 217/06 (2013.01); C07D 217/08 (2013.01); C07D 223/16 (2013.01); C07D 401/06 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/04 (2013.01); C07D 403/10 (2013.01); C07D 405/06 (2013.01); C07D 405/12 (2013.01); C07D 405/14 (2013.01); C07D 417/06 (2013.01)] 41 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
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.