Crystalline pharmaceutical and methods of preparation and use thereof
View Patent ↗Novel crystalline polymorphic forms, Forms A, B, C, D, and E of a compound of Formula I, which has been found to be a potent inhibitor of LFA-1, are disclosed. Methods of preparation and uses thereof in the treatment of LFA-1 mediated diseases are also disclosed in this invention.
1. A compound of the formula:
or its pharmaceutically acceptable salts.
2. A compound of the formula:
or its pharmaceutically acceptable salts.
3. A compound of the formula:
4. A compound of the formula:
or its pharmaceutically acceptable salts.
5. A reaction mixture comprising the compound of claim 1 or 2 , a solvent, and a coupling reagent.
6. The reaction mixture of claim 5 further comprising a base.
7. The reaction mixture of claim 6 comprising the compound of
or its pharmaceutically acceptable salts.
8. The reaction mixture of claim 7 wherein a compound of the formula:
is produced.
9. The reaction mixture of claim 5 wherein the solvent is DMF.
10. The reaction mixture of claim 5 wherein the coupling reagent is 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU).
11. The reaction mixture of claim of claim 6 wherein the base is triethylamine.
12. A compound of the formula:
13. A reaction mixture comprising the compound of claim 4 , a solvent, and an acid.
14. The reaction mixture of claim 4 wherein a compound of the formula:
is produced.
15. The reaction mixture of claim 13 wherein the solvent is dioxane.
16. The reaction mixture of claim 13 wherein the acid is HCl.
17. A reaction mixture comprising the compound of claim 12 , a solvent, and a base.
18. The reaction mixture of claim 17 further comprising benzofuranoyl chloride.
19. The reaction mixture of claim 18 wherein a compound of the formula:
is produced.
20. The reaction mixture of claim 17 wherein the solvent is methylene chloride.
21. The reaction mixture of claim 17 wherein the base is diisopropylethylamine.