Mitofusin activators and methods of use thereof
OwnerGerald W. Dorn, IIinventor
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Abstract
Compositions including small molecule mitofusin activators are described. The mitofusin activators 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. Methods of treatment, pharmaceutical formulations, and screening methods for identifying compounds that activate mitochondrial fusion are also described.
Claims18
A method comprising:
- administering a composition comprising one or more of a 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 formula of
- wherein:
- X is optionally substituted cycloalkyl or heterocycloalkyl;
- Z is optionally substituted pyridinyl or pyrimidinyl;
- Ra and Rb are independently selected from the group consisting of H, F, alkyl, and C3-7 cycloalkyl, or Ra and Rb taken together form a C3-7 cycloalkyl or heterocycloalkyl;
- Rc and Rd are independently selected from the group consisting of H, F, alkyl, and C3-7 cycloalkyl, or Rc and Rd taken together form a C3-7 cycloalkyl or heterocycloalkyl;
- Y is O, CReRf CReCRf, or cycloalkyl;
- Re and Rf are independently selected from the group consisting of H, F, alkyl, and cycloalkyl, or Re and Rf taken together form a C3-7 cycloalkyl or heterocycloalkyl;
- o is 0 or 1;
- p is 1;
- and
- q is 0, 1, 2, 3, or 4, provided that if Y is cycloalkyl, 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 one or more of a mitofusin activator or a pharmaceutically acceptable salt thereof, the mitofusin activator having a formula of
- wherein:
- X is optionally substituted cycloalkyl or heterocycloalkyl;
- Z is optionally substituted pyridinyl or pyrimidinyl;
- Ra and Rb are independently selected from the group consisting of H, F, alkyl, and C3-7 cycloalkyl, or Ra and Rb taken together form a C3-7 cycloalkyl or heterocycloalkyl;
- Rc and Rd are independently selected from the group consisting of H, F, alkyl, and C3-7 cycloalkyl, or Rc and Rd taken together form a C3-7 cycloalkyl or heterocycloalkyl,
- Y is O, CReRf CReCRf, or cycloalkyl;
- Re and Rf are independently selected from the group consisting of H, F, alkyl, and cycloalkyl, or Re and Rf taken together form a C3-7 cycloalkyl or heterocycloalkyl;
- o is 0 or 1;
- p is 1;
- and
- q is 0, 1, 2, 3, or 4, provided that if Y is cycloalkyl, 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.