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US 2021/0332012 A1Published application
N-substituted indoles and other heterocycles for treating brain disorders
AssigneeThe Regents of the University of California
InventorsDavid E. OLSON, Lee DUNLAP, Florence Wagner
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Abstract
The present invention provides N-substituted indoles and other heterocycles and methods of using the compounds for treating brain disorders.
Claims30
A compound of Formula I:
- wherein:
- X is CR3;
- R1a and R1b are each independently hydrogen, C1-6 alkyl, C3-8 cycloalkyl, or C4-14 alkyl-cycloalkyl;
- R1c is C1-6 alkyl, C3-8 cycloalkyl, or C4-14 alkyl-cycloalkyl;
- alternatively, two of R1a, R1b, and R1c are combined with the atoms to which they are attached to form a C3-12 heterocycloalkyl;
- R2, R3, R4, R5, R6 and R7 are each independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halogen, C1-6 haloalkyl, C1-6 alkylamine, C1-6 alkoxy, C1-6 haloalkoxy, —OR8a, —NO2, —CN, —C(O)R8b, —C(O)OR8b, —OC(O)R8b, —OC(O)OR8b, —N(R8bR8c), —N(R8b)C(O)R8c, —C(O)N(R8bR8c), —N(R8b)C(O)OR8c, —OC(O)N(R8bR8c), —N(R8b)C(O)N(R8cR8d), —C(O)C(O)N(R8bR8c), —S(O2)R8b, —S(O)2N(R8bR8c), C3-8 cycloalkyl, C3-14 alkyl-cycloalkyl, C4-10 heterocycloalkyl, C4-16 alkyl-heterocycloalkyl, C6-12 aryl, C7-18 alkyl-aryl, C5-10 heteroaryl, or C4-16 alkyl-heteroaryl;
- R8a is C3-8 cycloalkyl, C3-14 alkyl-cycloalkyl, C4-10 heterocycloalkyl, C4-16 alkyl-heterocycloalkyl, C6-12 aryl, C7-18 alkyl-aryl, C5-10 heteroaryl, or C4-16 alkyl-heteroaryl;
- R8b, R8c and R8d are each independently H or C1-6 alkyl;
- alternatively, one of R1a, R1b, or R1c is combined with R2 to form a C5-12 heterocycloalkyl;
- alternatively, R2 and R3 are combined with the atoms to which they are each attached to form a C4-8 cycloalkyl, C4-10 heterocycloalkyl, or C6-12 aryl;
- alternatively, R4 and R5, R5 and R6, or R6 and R7 are combined with the atoms to which they are each attached to form a C4-6 cycloalkyl, C4-6 heterocycloalkyl, C6-12 aryl, or C5-10 heteroaryl;
- and
- L is C1-6 alkylene,
- or pharmaceutically acceptable salts and isomers thereof,
- wherein when R1a, R1b and R1c are each Me, L is methylene, X is CR3 and R2, R3, R4, R5, R6 and R7 are hydrogen, then the compound is
- and
- wherein the compound is other than
14 more elements
A compound of Formula II:
- wherein:
- X is CR3;
- R1a and R1b are each independently hydrogen, C1-6 alkyl, C3-8 cycloalkyl, or C4-14 alkyl-cycloalkyl;
- alternatively, R1a and R1b are combined with the atoms to which they are attached to form a C3-12 heterocycloalkyl;
- R2, R3, R4, R5, R6 and R7 are each independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halogen, C1-6 haloalkyl, C1-6 alkylamine, C1-6 alkoxy, C1-6 haloalkoxy, —OR8a, —NO2, —CN, —C(O)R8b, —C(O)OR8b, —OC(O)R8b, —OC(O)OR8b, —N(R8bR8c), —N(R8b)C(O)R8c, —C(O)N(R8bR8c), —N(R8b)C(O)OR8c, —OC(O)N(R8bR8c), —N(R8b)C(O)N(R8cR8d), —C(O)C(O)N(R8bR8c), —S(O2)R8b, —S(O)2N(R8bR8c), C3-8 cycloalkyl, C3-14 alkyl-cycloalkyl, C4-10 heterocycloalkyl, C4-16 alkyl-heterocycloalkyl, C6-12 aryl, C7-18 alkyl-aryl, C5-10 heteroaryl, or C4-16 alkyl-heteroaryl;
- R8a is C3-8 cycloalkyl, C3-14 alkyl-cycloalkyl, C4-10 heterocycloalkyl, C4-16 alkyl-heterocycloalkyl, C6-12 aryl, C7-18 alkyl-aryl, C5-10 heteroaryl, or C4-16 alkyl-heteroaryl;
- R8b, R8c and R8d are each independently H or C1-6 alkyl;
- alternatively, one of R1a or R1b is combined with R2 to form a C5-12 heterocycloalkyl;
- alternatively, R2 and R3 are combined with the atoms to which they are each attached to form a C4-8 cycloalkyl, C4-10 heterocycloalkyl, or C6-12 aryl;
- alternatively, R4 and R5, R5 and R6, or R6 and R7 are combined with the atoms to which they are each attached to form a C4-6 cycloalkyl, C4-6 heterocycloalkyl, C6-12 aryl, or C5-10 heteroaryl;
- and
- L is C1-6 alkylene,
- or pharmaceutically acceptable salts and isomers thereof,
- wherein when R1a and R1b are both Me, and L is methylene, then at least one of R2, R3, R4, R5, R6, and R7 is not hydrogen and the compound is other than:
- wherein when R1a and R1b are Me, L is ethylene, and X is CR3, then at least one of R2, R3, R4, R5, R6 and R7 is not hydrogen;
- wherein when R1c is hydrogen, and R5 is Br, Cl, F, —NH2, —NO2, or C1-3 alkoxy, then at least one of R2, R3, R4, R6, or R7 is not hydrogen;
- and
- wherein when R1c is hydrogen and R5 is F, then at least one of R2, R3, R4, R6, or R7 is not hydrogen and R6 is not F.
15 more elements
Dependencies are inferred from the claim text.