Crystalline Pharmaceutical and Methods of Preparation and Use Thereof

• US 20150183765A1
• Filed: 12/01/2014
• Published: 07/02/2015
• Est. Priority Date: 10/21/2009
• Status: Active Grant

• Current Assignee: Bausch + Lomb Ireland Ltd. (Bausch Health Cos., Inc.)
• Original Assignee: Sarcode Bioscience Inc. (Shire plc)
• Inventors: BURNIER, John
• Granted Patent: US 9,353,088 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/10 linked by a carbon chain containing aromatic rings

Abstract

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.

Claims

1. A method of synthesizing a compound of Formula I:

2. The method of claim 1, wherein the aprotic solvent is dioxane.

3. The method of claim 1, wherein the base is sodium hydroxide.

4. The method of claim 1, wherein R is a substituted or unsubstituted group selected from lower alkyl, lower alkenyl, lower alkynyl, cyclo(lower)alkyl, cyclo(lower)alkenyl, aryl, aralkyl, heterocyclyl, and heteroaryl groups.

5. The method of claim 1, comprising the steps:

a) base hydrolysis of Formula A;

6. The method of claim 5, wherein the aprotic solvent is dioxane.

7. The method of claim 5, wherein the base is sodium hydroxide.

15. An isolated compound of Formula I:

8. A method of synthesizing a compound of Formula I:

9. The method of claim 8, wherein the aprotic solvent is dioxane.

10. The method of claim 8, wherein the acid is hydrogen chloride.

11. The method of claim 8, wherein R is a substituted or unsubstituted group selected from lower alkyl, lower alkenyl, lower alkynyl, cyclo(lower)alkyl, cyclo(lower)alkenyl, aryl, aralkyl, heterocyclyl, and heteroaryl groups.

12. The method of claim 8, comprising the steps:

a) acid hydrolysis of Formula A;

13. The method of claim 12, wherein the aprotic solvent is dioxane.

14. The method of claim 12, wherein the acid is hydrogen chloride.