Trans-4-hydroxycyclohexyl phenyl amide mitofusin activators and methods of use thereof
AssigneeMitochondria Emotion, Inc.
InventorGerald W. DORN, II
Life of this patent
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Abstract
Compounds and compositions including stereoisomers of 6-phenylhexanamide derivative small molecule mitofusin activators are described. In particular, mitofusin activators comprising derivatives of (trans-4-hydroxycyclohexyl)-6-phenylhexanamide, which are useful for treating diseases or disorders associated with a mitochondria-associated disease, disorder, or condition such as diseases or disorders associated with mitofusin-1 (MFN1) and/or mitofusin-2 (MFN2), or mitochondrial dysfunction, are described. Methods of treatment and pharmaceutical formulations are also described.
Claims22
A method comprising:
- administering a therapeutically effective amount of a composition comprising one or more of mitofusin activator or a pharmaceutically acceptable salt thereof to a subject having or suspected of having a mitochondria-associated disease, disorder or condition, the mitofusin activator having a structure represented by the following formula:
- wherein:
- Z is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
- R2 and R3 are independently selected from H, F, alkyl, and C3-7 cycloalkyl, or R2 and R3 taken together form a C3-7 cycloalkyl or heterocycloalkyl;
- R4 and R5 are independently selected from H, F, alkyl, and C3-7 cycloalkyl, or R4 and R5 taken together form a C3-7 cycloalkyl or heterocycloalkyl;
- Y is O, CR6R7, CR8═CR9, C≡C, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, NR8, S, SO2, SONR9, NR9SO2, NR8CO, CONR8, or NR8CONR9;
- R6 is H, F, alkyl, or cycloalkyl, R7 is H, F, alkyl, or cycloalkyl, or R6 and R7 taken together form a C3-7 cycloalkyl or heterocycloalkyl;
- R8 is H, alkyl, or C3-7 cycloalkyl, R9 is H, alkyl, or C3-7 cycloalkyl, or R8 and R9 taken together form a C3-7 cycloalkyl;
- o is 0, 1, 2, 3, 4 or 5;
- p is 0 or 1;
- and
- q is 0, 1, 2, 3, 4 or 5, provided that if Y is cycloalkyl and p is 1 the sum of o+p+q is not less than 3 or greater than 5, and otherwise the sum of o+p+q is 5.
A composition comprising:
- a mitofusin activator or a pharmaceutically acceptable salt thereof, the mitofusin activator having a structure represented by the following formula:
- wherein:
- Z is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
- R2 and R3 are independently selected from H, F, alkyl, and C3-7 cycloalkyl, or R2 and R3 taken together form a C3-7 cycloalkyl or heterocycloalkyl;
- R4 and R5 are independently selected from H, F, alkyl, and C3-7 cycloalkyl, or R4 and R5 taken together form a C3-7 cycloalkyl or heterocycloalkyl;
- Y is O, CR6R7, CR8═CR9, C≡C, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, NR8, S, SO2, SONR9, NR9SO2, NR8CO, CONR8, or NR8CONR9;
- R6 is H, F, alkyl, or cycloalkyl, R7 is H, F, alkyl, or cycloalkyl, or R6 and R7 taken together form a C3-7 cycloalkyl or heterocycloalkyl;
- R8 is H, alkyl, or C3-7 cycloalkyl, R9 is H, alkyl, or C3-7 cycloalkyl, or R8 and R9 taken together form a C3-7 cycloalkyl;
- o is 0, 1, 2, 3, 4 or 5;
- p is 0 or 1;
- and
- q is 0, 1, 2, 3, 4 or 5, provided that if Y is cycloalkyl and p is 1 the sum of o+p+q is not less than 3 or greater than 5, and otherwise the sum of o+p+q is 5.
Dependencies are inferred from the claim text.