Compounds and methods for leukotriene biosynthesis inhibition
View Patent ↗This invention provides novel salt and crystalline forms thereof of (−)4-(4-fluorophenyl)-7-[({5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-yl}amino)-methyl]-2H-chromen-2-one. The compounds are 5-LO inhibitors and are useful for treatment of conditions such as asthma, allergic rhinitis, COPD, and atherosclerosis.
1. Crystalline p-toluenesulfonic acid salt of (−)4-(4-fluorophenyl)-7-[({5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-yl}amino)methyl]-2H-chromen-2-one characterized by having an XRPD pattern obtained using CuKα radiation containing at least one d-spacing selected from 17.77, 8.90 and 5.17.
2. Crystalline p-toluenesulfonic acid salt of (−)4-(4-fluorophenyl)-7-[({5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-yl}amino)methyl]-2H-chromen-2-one characterized by having at least one chemical shift value obtained by solid-state carbon-13 CPMAS NMR selected from the group consisting of 48.5, 124.1, 152.4, 28.4, 141.3, 162.1, 74.8, 154.4 and 164.5 parts per million.
3. Crystalline p-toluenesulfonic acid salt of (−)4-(4-fluorophenyl)-7-[({5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-yl}amino)methyl]-2H-chromen-2-one characterized by having at least two chemical shift values obtained by solid-state carbon-13 CPMAS NMR selected from the group consisting of 48.5, 124.1, 152.4, 28.4, 141.3, 162.1, 74.8, 154.4 and 164.5 parts per million.
4. Crystalline p-toluenesulfonic acid salt of (−)4-(4-fluorophenyl)-7-[({5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-yl}amino)methyl]-2H-chromen-2-one characterized by having at least one chemical shift value obtained by solid-state fluorine-19 CPMAS NMR selected from the group consisting of −50.2, −75.6 and −101.3.
5. Crystalline p-toluenesulfonic acid salt of (−)4-(4-fluorophenyl)-7-[({5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-yl}amino)methyl]-2H-chromen-2-one characterized by having at least two chemical shift values obtained by solid-state fluorine-19 CPMAS NMR selected from the group consisting of −50.2, −75.6 and −101.3.
6. A pharmaceutical composition comprising a crystalline p-toluenesulfonic acid salt selected from the group consisting of:
(a) a salt characterized by having at least one chemical shift value obtained by solid-state carbon-13 CPMAS NMR selected from the group consisting of 48.5, 124.1, 152.4, 28.4, 141.3, 162.1, 74.8, 154.4 and 164.5 parts per million;
(b) a salt characterized by having at least two chemical shift values obtained by solid-state carbon-13 CPMAS NMR selected from the group consisting of 48.5, 124.1, 152.4, 28.4, 141.3, 162.1, 74.8, 154.4 and 164.5 parts per million;
(c) a salt characterized by having at least one chemical shift value obtained by solid-state fluorine-19 CPMAS NMR selected from the group consisting of −50.2, −75.6 and −101.3; and
(d) a salt characterized by having at least two chemical shift values obtained by solid-state fluorine-19 CPMAS NMR selected from the group consisting of −50.2, −75.6 and −101.3;
and a pharmaceutically acceptable carrier.