TREATMENT AND PREVENTION OF INTESTINAL INFLAMMATORY DISEASES WITH A BILE ACID DERIVATIVE
The present application relates to methods of treating or preventing an intestinal inflammatory disease or condition (e.g., intestinal ischemia reperfusion injury) in a subject in need thereof, comprising administering a therapeutically effective amount of a compound of the application.
1 . A method of treating an intestinal inflammatory disease or condition in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula A:
or a pharmaceutically acceptable salt or amino acid conjugate thereof, wherein:
R 1 is C 1 -C 6 alkyl;
R 2 , R 3 , R 5 , and R 6 are each independently H or OH;
R 4 is CO 2 H or OSO 3 H; and
R 7 is H or C 1 -C 6 alkyl.
2 . The method of claim 1 , comprising administering to the subject a compound of formula 1:
or a pharmaceutically acceptable salt thereof.
3 . The method of claim 1 or 2 , comprising administering to the subject a compound of formula 1-Na:
4 . The method of claim 1 or 2 , comprising administering to the subject a compound of formula 1-TEA:
5 . The method of any one of the preceding claims, wherein the disease or condition is modulated by FXR.
6 . The method of any one of the preceding claims, wherein the disease or condition is modulated by TGR5.
7 . The method of any one of the preceding claims, wherein the disease is intestinal ischemia reperfusion injury.
8 . A method of reducing intestinal permeability in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula A:
or a pharmaceutically acceptable salt or amino acid conjugate thereof, wherein:
R 1 is C 1 -C 6 alkyl;
R 2 , R 3 , R 5 , and R 6 are each independently H or OH;
R 4 is CO 2 H or OSO 3 H; and
R 7 is H or C 1 -C 6 alkyl.
9 . A method of stimulating intestinal recovery through GLP-1 upregulation in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula A:
or a pharmaceutically acceptable salt or amino acid conjugate thereof, wherein:
R 1 is C 1 -C 6 alkyl;
R 2 , R 3 , R 5 , and R 6 are each independently H or OH;
R 4 is CO 2 H or OSO 3 H; and
R 7 is H or C 1 -C 6 alkyl.