Mitofusin activators and methods of use thereof
AssigneeMitochondria Emotion, Inc.
InventorGerald W. Dorn, II
Life of this patent
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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.
Claims25
A method comprising:
- administering a therapeutically effective amount of 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 selected from cycloalkyl and heterocycloalkyl,
- Z is aryl;
- Ra and Rb are independently selected from 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 H, F, alkyl, CORg, and C3-7 cycloalkyl, or Rc and Rd taken together form a C3-7 cycloalkyl or heterocycloalkyl;
- Y is selected from O, CReRf, CRe═CRf, C≡C cycloalkyl, heterocycloalkyl, aryl, heteroaryl, NRg, S, SO2, SONRh, NRgSO2, NRgCO, CONRg, and NRgCONRh;
- Re and Rf are independently selected from H, F, alkyl, and cycloalkyl, or Re and Rf taken together form C3-7 cycloalkyl or heterocycloalkyl;
- Rg is selected from H, alkyl, and C3-7 cycloalkyl;
- Rh is selected from H, alkyl, CORg, and C3-7 cycloalkyl;
- o is 0, 1, 2, 3, 4, or 5;
- p is O 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 one or more of a mitofusin activator or a pharmaceutically acceptable salt thereof, the mitofusin activator having a formula of
- wherein:
- X is selected from cycloalkyl and heterocycloalkyl,
- Z is aryl;
- Ra and Rb are independently selected from 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 H, F, alkyl, CORg, and C3-7 cycloalkyl, or Rc and Rd taken together form a C3-7 cycloalkyl or heterocycloalkyl;
- Y is selected from O, CReRf, CRe═CRf, C≡C cycloalkyl,
- heterocycloalkyl, aryl, heteroaryl, NRg, S, SO2, SONRh, NRgSO2, NRgCO, CONRg, and NRgCONRh;
- Re and Rf are independently selected from H, F, alkyl, and cycloalkyl, or Re and Rf taken together form C3-7 cycloalkyl or heterocycloalkyl;
- Rg is selected from H, alkyl, and C3-7 cycloalkyl;
- Rh is selected from H, alkyl, CORg, and C3-7 cycloalkyl;
- o is 0, 1, 2, 3, 4, or 5;
- p is O 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.