Co-crystals of pyrrolidinones
View Patent ↗The present invention relates to new co-crystals of pyrrolidinones having the formula (I) wherein R 1 is a C- 1 -C 6 alkyl group. R 2 is a C- 1 -C 6 alkyl group which is optionally substituted by 1 to 3 halogens or R 2 is a C 2 -C 6 alkenyl group.
1. A co-crystal comprising a pyrrolidinone having the formula (I)
wherein
R 1 is a C 1 -C 6 alkyl group;
R 2 is a C 1 -C 6 alkyl group which is optionally substituted by 1 to 3 halogens or R 2 is a C 2 -C 6 alkenyl group;
and one or more salts selected of the group consisting of MgCl 2 , MgSO 4 , MgBr 2 , Mg 3 (PO4) 2 , MgHPO4, Mg(H 2 PO 4 ) 2 , MgCO 3 , Mg(HCO 3 ) 2 , CaCl 2 , CaSO 4 , CaBr 2 , CaCO 3 , Mg(HCO 3 ) 2 , Ca 3 (PO4) 2 , CaHPO4, Ca(H 2 PO 4 ) 2 , KCl, KBr, K 2 SO 4 , KHSO 4 , K 2 CO 3 , K 2 HPO 4 , KH 2 PO 4 , K 3 PO 4 , NaCl, NaBr, Na 2 SO 4 , Na 2 CO 3 , Na 2 HPO 4 , NaH 2 PO 4 , Na 3 PO 4 , NH 4 Cl, NH 4 Br, (NH 4 ) 2 SO 4 , (NH 4 ) 2 CO 3 , (NH 4 ) 2 HPO 4 , NH 4 H 2 PO 4 , Na 3 PO 4 and their hydrates, or a magnesium, calcium, potassium, sodium, or ammonium salt of malic acid, maleic acid, citric acid, pamoic acid, acetic acid, lactic acid, fumaric acid, methyl sulfonic acid, mesylic acid, or ascorbic acid.
2. The co-crystal according to claim 1 , wherein the salt is selected from MgCl 2 , MgSO 4 , MgBr 2 , Mg 3 (PO4) 2 , MgHPO4, Mg(H 2 PO 4 ) 2 , MgCO 3 , Mg(HCO 3 ) 2 , Mg(HCO 3 ) 2 .
3. The co-crystal according to claim 2 , wherein the salt is MgCl 2 .
4. The co-crystal according to claim 3 , which is a hydrate.
5. The co-crystal according to claim 1 , wherein the pyrrolidinone having the formula (I) is (2S)-2-(2-oxo-4-n-propyl-1-pyrrolidinyl)butanamide.
6. The co-crystal according to claim 1 , wherein the pyrrolidinone having the formula (I) is ((2S)-2-((4R)-2-oxo-4-n-propyl-1-pyrrolidinyl)butanamide
7. The co-crystal according to claim 6 wherein the stoichiometry of the co-crystal is as follows: ((2S)-2-((4R)-2-oxo-4-n-propyl-1-pyrrolidinyl)butanamide×0.5 MgCl 2 ×2 H 2 O.
8. The co-crystal according to claim 7 , characterized by an x-ray powder diffraction pattern as follows: 7.44, 11.74, 12.26, 13.40, 14.92, 15.82, 18.64, 21.40, 21.80, 22.14, 22.68, 23.60, 23.70, 25.12 and 26.80 degrees 2-theta.
9. A pharmaceutical composition which comprises a co-crystal according to claim 1 , 5 , 6 , or 7 together with a pharmaceutically acceptable excipient.
10. A method for treating epilepsy, epileptogenesis, and convulsions, the method comprising administering an effective amount of a co-crystal according to claim 1 , 5 , 6 , or 7 .