SOLID FORMS OF (Z)-4-(5-((3-BENZYL-4-OXO-2-THIOXOTHIAZOLIDIN-5-YLIDENE) METHYL)FURAN-2-YL)BENZOIC ACID
The present invention provides new salts and crystalline forms of leukadherin LA1 [(Z)-4-(5-((3-benzyl-4-oxo-2-thioxothiazolidin-5-ylidene)methyl)furan-2-yl)benzoic acid] according to Formula I. Methods for preparation of the salts and crystalline forms are also described, as well as methods for treating β2 integrin-mediated diseases and conditions using the salts and crystalline forms.
1 - 58 . (canceled)
59 . A method for preparing a LA1 salt, the method comprising:
contacting LA1 free acid with a base in a solvent to form a reaction mixture; and
waiting a sufficient time to form a LA1 salt.
60 . The method of claim 59 , wherein the solvent is a member selected from the group consisting of tetrahydrofuran, dioxane, methanol, ethanol, isopropanol, N,N-dimethylformamide, N-methylpyrollidone, methyl tert-butyl ether, acetone, ethyl acetate, dichloromethane, water, and a mixture thereof.
61 . The method of claim 59 , wherein the solvent is a member selected from the group consisting of tetrahydrofuran, methanol acetone, ethanol and a mixture thereof.
62 . The method of claim 59 , wherein the reaction mixture is heated from about 25° C. to about 80° C.
63 . The method of claim 59 , wherein the sufficient time is from about 15 minutes to about 72 hours or longer.
64 . The method of claim 59 , wherein the base is a member selected from the group consisting of ammonia, L-arginine, calcium hydroxide, choline, meglumine, magnesium hydroxide, benethamine, benzathine, betaine, deanol, diethylamine, 2-diethylaminoethanol, hydrabamine, 1-(2-hydroxyethyl)-pyrrolidine, t-butylamine, tromethamine, piperazine, imidazole, ethylenediamine, ethanolamine, diethanolamine, and triethanolamine.
65 . The method of claim 59 , wherein the base is a member selected from the group consisting of ammonia, L-arginine, calcium hydroxide, choline, meglumine, and magnesium hydroxide.
66 . The method of claim 59 , wherein the LA1 salt is a choline salt according to the formula:
67 . The method of claim 66 , wherein the LA1 choline salt is recrystallized to form a crystalline form.
68 . The method of claim 67 , wherein the LA1 choline crystalline form is a member selected from the group consisting of form G, form O, form Q, form R and form S.
69 . The method of claim 59 , wherein the LA1 salt is a meglumine salt of LA1 according to formula:
70 . The method of claim 68 , wherein the LA1 megluamine salt is recrystallized to form a crystalline form.
71 . The method of claim 70 , wherein the LA1 megluamine crystalline form is a member selected from the group consisting of form H, form L, form M, form N and form T.