Therapeutic compounds
AssigneesRegents of the University of Minnesota, The Board of Regents of the University of Oklahoma, Wake Forest University Health Sciences
InventorsAdam Duerfeldt, Julia Lee, Ziwei Hu, Dinesh Nath, Jian-Xing Ma, Bo HU
Life of this patent
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Abstract
The invention provides a compound of formula (I): or a salt thereof, wherein A, B, C, R1, and R have any of the values described in the specification, as well as compositions comprising a compound of formula (I). The compounds are useful for agonizing the activity of PPARα and for treating diseases modulated by PPARα, such as, for example, diabetic retinopathy, pain, and liver diseases including fibrosis, NASH and NAFLD. Certain compounds are also useful as both agonists of PPARα and inhibitors of STING.
Claims66
A compound of formula (I):
- or a salt thereof, wherein:
- R is —COOR2, —CN, or 5-tetrazolyl;
- ring A is additionally optionally substituted with one or more groups independently selected from the group consisting of halo, hydroxy, (C1-C4)alkyl, (C1-C6)alkoxy, and NRaRb;
- B is phenyl, a 5-membered heteroaryl, or a 6-membered heteroaryl;
- R1 is H, halo, cyano, (C1-C4)alkyl, (C3-C6)cycloalkyl, (C1-C4)alkylsulfonyl, hydroxy, or (C1-C4)alkoxy, which (C1-C4)alkyl, (C3-C6)cycloalkyl, and (C1-C4)alkoxy is optionally substituted with one or more groups independently selected from halo;
- R2 is H or (C1-C4)alkyl;
- B is additionally optionally substituted with one or more groups Rx that are independently selected from the group consisting of (C1-C4)alkyl, hydroxy, (C1-C4)alkoxy, nitro, and halo, wherein any (C1-C4)alkyl, and (C1-C4)alkoxy is optionally substituted with one or more groups independently selected from halo;
- ring C is additionally optionally substituted with one or more groups Ry that are that are independently selected from the group consisting of (C1-C4)alkyl, hydroxy, (C1-C4)alkoxy, nitro, NRcRd;
- and halo, wherein any (C1-C4)alkyl, and (C1-C4)alkoxy is optionally substituted with one or more groups independently selected from halo;
- each Ra and Rb is independently selected from the group consisting of H, (C1-C4)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-46)alkyl, and (C1-C4)alkanolyl, or Ra and Rb together with the nitrogen to which they are attached form a aziridino, azetidino, morpholino, piperazino, pyrrolidino or piperidino;
- and
- each Rc and Rd is independently selected from the group consisting of H, (C1-C4)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-46)alkyl, and (C1-C4)alkanolyl, or Rc and Rd together with the nitrogen to which they are attached form a aziridino, azetidino, morpholino, piperazino, pyrrolidino or piperidino.
A compound or salt that modulates the activity of PPARα and STING.
A compound or salt that has agonist activity of PPAR-alpha of less than 5 μM and that inhibits STING at less than 10 μM.
A compound selected from:
- or a salt thereof.
A method for treating a disease in an animal where both PPARα and STING are implicated and modulation of both targets may be beneficial, comprising administering to the animal, a compound or salt that is a dual modulator of PPARα and STING.
A method for treating a disease in an animal where agonism of PPAR-alpha and inhibition of STING are both implicated, comprising administering to the animal, a compound or pharmaceutically acceptable salt that is an agonist of PPARα and an inhibitor of STING.
A compound or salt that modulates the activity of PPARα and STING for use in medical therapy.
A compound or salt that modulates the activity of PPARα and STING for the prophylactic or therapeutic treatment of a disease or condition where both PPARα and STING are implicated and modulation of both PPARα and STING may be beneficial.
A compound or salt that has dual activity as an agonist of PPAR-alpha and as an inhibitor of STING for the prophylactic or therapeutic treatment of a disease or condition wherein agonism of PPAR-alpha and as an inhibition of STING may be beneficial.
The use of a compound or salt that modulates the activity of PPARα and STING to prepare a medicament for treating a disease or condition where both PPARα and STING are implicated and modulation of both PPARα and STING may be beneficial.
The use of a compound or salt that has dual activity as an agonist of PPAR-alpha and as an inhibitor of STING to prepare a medicament for treating a disease or condition wherein agonism of PPAR-alpha and as an inhibition of STING may be beneficial.
Dependencies are inferred from the claim text.