Fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives
The invention relates to fluorinated compounds and their use as integrin receptor antagonists. Novel fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives and pharmaceutically acceptable salts or solvates thereof and their use are described.
1. A compound of formula III:
or a pharmaceutically acceptable salt or solvate thereof, wherein
R 1 is C 1 -C 6 alkoxy wherein said C 1 -C 6 alkoxy is substituted with 0, 1, 2, 3, 4, or 5 fluorine atoms; and
R 2 and R 3 are each independently selected from H and F,
provided that the compound of formula III contains at least one fluorine atom.
2. The compound of claim 1 , wherein R 1 is selected from OCH 2 F, OCHF 2 , and OCF 3 .
3. The compound of claim 1 , wherein R 1 is OCF 3 .
4. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutical carrier, diluent, or excipient.
5. A pharmaceutical composition comprising a compound of claim 2 or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutical carrier, diluent, or excipient.
6. A pharmaceutical composition comprising a compound of claim 3 or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutical carrier, diluent, or excipient.
7. A method of inhibiting bone resorption or vascular restenosis, promoting would healing, or treating or preventing osteoporosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammation, viral diseases, tumor growth, or metastasis, comprising administering to the subject a therapeutically effective amount of a compound of formula I:
or a pharmaceutically acceptable salt or solvate thereof, wherein
X is selected from CH and N;
Y is selected from CH and N;
R 1 is C 1 -C 6 alkoxy wherein said C 1 -C 6 alkoxy is substituted with 0, 1, 2, 3, 4, or 5 fluorine atoms; and
R 2 and R 3 are each independently selected from H and F, or R 2 and R 3 taken together with the carbon atom to which they are attached form a 3- or 4-membered carbocyclic or heterocyclic ring,
provided that the compound of formula I contains at least one fluorine atom.
8. The method of claim 7 , wherein the compound is of formula III:
or a pharmaceutically acceptable salt or solvate thereof, wherein
R 1 is C 1 -C 6 alkoxy wherein said C 1 -C 6 alkoxy is substituted with 0, 1, 2, 3, 4, or 5 fluorine atoms; and
R 2 and R 3 are each independently selected from H and F,
provided that the compound of formula III contains at least one fluorine atom.
9. The method of claim 7 , wherein the compound is
or a pharmaceutically acceptable salt or solvate thereof.
10. The method of claim 7 , further comprising administering to the subject a second therapy.
11. The method of claim 10 , wherein the second therapy is an inhibitor of VEGF.
12. The compound of claim 1 , wherein R 2 and R 3 are both H.
13. The compound of claim 1 , being
or a pharmaceutically acceptable salt or solvate thereof.
14. A pharmaceutical composition comprising a compound of claim 12 or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutical carrier, diluent, or excipient.
15. A pharmaceutical composition comprising a compound of claim 13 or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutical carrier, diluent, or excipient.
16. The method of claim 11 , wherein the inhibitor of VEGF is administered orally, intravenously, intraperitoneally, topically, subcutaneously, intramuscularly, or transdermally.
17. The method of claim 16 , wherein the inhibitor of VEGF is administered intravenously.