Lactam compound
| Title: | Lactam compound |
|---|---|
| Patent Number: | 7,468,365 |
| Publication Date: | December 23, 2008 |
| Appl. No: | 11/329859 |
| Application Filed: | January 11, 2006 |
| Abstract: | The present invention provides crystalline (N)-((S)-2-hydroxy-3-methyl-butyryl)-1-(L-alaninyl)-(S)-1-amino-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one, a crystalline anydrate and dihydrates thereof, compositions comprising (N)-((S)-2-hydroxy-3-methyl-butyryl)-1-(L-alaninyl)-(S)-1-amino-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one, its crystalline anhydrate or dihydrate, and methods for using the same. |
| Inventors: | Audia, James Edmund (Zionsville, IN, US); Diseroad, Benjamin Alan (Martinsville, IN, US); John, Varghese (San Francisco, CA, US); Latimer, Lee H. (Oakland, CA, US); Nissen, Jeffrey Scott (Indianapolis, IN, US); Stephenson, Gregory Alan (Fishers, IN, US); Thorsett, Eugene D. (Half Moon Bay, CA, US); Tung, Jay S. (Belmont, CA, US) |
| Assignees: | Eli Lilly and Company (Indianapolis, IN, US), Elan (South San Francisco, CA, US) |
| Claim: | 1. (N)-((S)-2-Hydroxy-3-methyl-butyryl)-1-(L-alaninyl)-(S)-1-amino-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one or the dihydrate thereof. |
| Claim: | 2. The compound of claim 1 as the anhydrate. |
| Claim: | 3. The compound of claim 2 as the crystalline anhydrate Form-α characterized by at least one of the following: a) an X-ray powder diffraction pattern comprising a peak at 4.53, 5.36, 9.52, 9.79, 11.69, 12.46, 13.91, 14.72, 16.21, 17.92, or 19.10 (2θ±0.2°); b) an X-ray powder diffraction pattern comprising peaks at 9.52 and 9.79 (2θ±0.2°); 4.53 and 9.52 (2θ±0.2°); 4.53 and 9.79 (2θ±0.2°); or 9.52, 9.79, and 12.46 (2θ±0.2°); c) a solid state 13 C nuclear magnetic resonance spectrum having a peak at chemical shift 78.0, 79.0, 122.9, 135.5, 168.6, 169.5, or 177.8±0.1 ppm; and d) a DSC melting point of 214° C. |
| Claim: | 4. The compound of claim 2 as the crystalline anhydrate Form-β characterized by at least one of the following: a) an X-ray powder diffraction pattern comprising a peak at 8.10, or 10.66 (20±0.2°); b) a solid state 13 C nuclear magnetic resonance spectrum having a peak at chemical shift 19.1, 77.2, or 130.5+/−0.1 ppm; and c) a DSC melting point of 217° C. |
| Claim: | 5. The compound of claim 1 as the dihydrate in the crystalline form characterized by at least one of the following: a) an X-ray powder diffraction pattern comprising a peak at 8.36, 12.43, 15.34, 19.22, 20.50, or 20.63 (2θ±0.2°); b) an X-ray powder diffraction pattern comprising peaks at 8.36 and 15.34 (2θ±0.2°); 8.36 and 12.43 (2θ±0.2°); 8.36, 12.43, and 15.34 (2θ±0.2°); c) a solid state 13 C nuclear magnetic resonance spectrum having a peak at chemical shift 75.6, 35.3, 21.4, or 16.6±0.5 ppm. |
| Claim: | 6. A pharmaceutical composition comprising (N)-((S)-2-hydroxy-3-methyl-butyryl)-1-(L-alaninyl)-(S)-1-amino-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one or the dihydrate thereof and a pharmaceutically acceptable diluent. |
| Claim: | 7. A pharmaceutical composition of claim 6 comprising (N)-((S)-2-hydroxy-3-methyl-butyryl)-1-(L-alaninyl)-(S)-1-amino-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one anhydrate. |
| Claim: | 8. A pharmaceutical composition of claim 7 wherein (N)-((S)-2-hydroxy-3-methyl-butyryl)-1-(L-alaninyl)-(S)-1-amino-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one is in crystalline anhydrate Form-α. |
| Claim: | 9. A pharmaceutical composition of claim 7 wherein (N)-((S)-2-hydroxy-3-methyl-butyryl)-1-(L-alaninyl)-(S)-1-amino-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one is in crystalline anhydrate Form-β. |
| Claim: | 10. A pharmaceutical composition of claim 6 comprising (N)-((S)-2-hydroxy-3-methyl-butyryl)-1-(L-alaninyl)-(S)-1-amino-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one dihydrate and a pharmaceutically acceptable diluent. |
| Claim: | 11. A method of treating Alzheimer's disease comprising administering to a patient in need thereof with an effective amount of (N)-((S)-2-hydroxy-3-methyl-butyryl)-1-(L-alaninyl)-(S)-1-amino-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one or the dihydrate thereof. |
| Claim: | 12. A method of claim 11 comprising administering (N)-((S)-2-hydroxy-3-methyl-butyryl)-1-(L-alaninyl)-(S)-1-amino-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one anhydrate. |
| Claim: | 13. A method of claim 12 wherein (N)-((S)-2-hydroxy-3-methyl-butyryl)-1-(L-alaninyl)-(S)-1-amino-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one anhydrate is in crystalline Form-α. |
| Claim: | 14. A method of claim 12 wherein (N)-((S)-2-hydroxy-3-methyl-butyryl)-1-(L-alaninyl)-(S)-1-amino-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one anhydrate is in crystalline Form-β. |
| Claim: | 15. A method of claim 11 comprising administering (N)-((S)-2-hydroxy-3-methyl-butyryl)-1-(L-alaninyl)-(S)-1-amino-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one dihydrate. |
| Current U.S. Class: | 51421/207 |
| Patent References Cited: | 5283241 February 1994 Bochis et al. 5284841 February 1994 Chu et al. 5596000 January 1997 Esser et al. 6635632 October 2003 Wu et al. 7153847 December 2006 Wu et al. WO 98/28268 July 1998 WO 02/40421 May 2002 WO 02/40508 May 2002 WO 02/47671 June 2002 |
| Other References: | Reiffen, Manred et al., Specific Bradycardic Agents. 1. Chemistry, Pharmacology, and Structure-Activity Relationships of Substituted Benzazepinones, a New Class of Compounds Exerting Antiischemic Properties, J. Med. Chem., 1990, 1496-1504, 33(5). cited by other Devita, Roberg J. et al., Heterocyclic analogs of the Benzolactam Nucleus of the Non-Peptidic Growth Hormone Secretagogue L-692,429, Bioorganic & Medicinal Chemistry Letters, 1995, 1281-1286, 5(12). cited by other |
| Primary Examiner: | Kifle, Bruck |
| Attorney, Agent or Firm: | Titus, Robert D. |
| Accession Number: | edspgr.07468365 |
| Database: | USPTO Patent Grants |
| Language: | English |
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