1,8-naphthyridine compounds for the treatment of cancer
View Patent ↗Compounds and compositions for treating, preventing or managing cancer are disclosed. The compositions provided herein comprise SNS-595 and N-desmethyl-SNS-595. Also provided are pharmaceutical compositions comprising the compounds and methods of treatment using the compounds and compositions.
1. A hydrate of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, wherein the hydrate exhibits an X-ray powder diffraction pattern comprising a peak at approximately 8.2 degrees 2θ.
2. The hydrate of claim 1 that exhibits an X-ray powder diffraction pattern further comprising peaks at approximately 6.9, 11.1 and 18.8 degrees 2θ.
3. The hydrate of claim 2 that exhibits an X-ray powder diffraction pattern further comprising peaks at approximately 16.4, 17.5, 20.8 and 24.9 degrees 2θ.
4. A hydrate of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, wherein the hydrate exhibits a differential scanning calorimetry thermogram comprising an endothermic event with an onset temperature of approximately 126.5° C. when heated from approximately 25° C. to approximately 350° C. at approximately 10° C./min.
5. The hydrate of claim 4 that exhibits a differential scanning calorimetry thermogram further comprising an endothermic event with an onset temperature of approximately 273.3° C.
6. A hydrate of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, wherein the hydrate exhibits a thermogravimetric analysis thermogram comprising a weight loss of approximately 4.4% when heated from approximately 25° C. to approximately 200° C. at approximately 10° C./min.
7. A hydrate of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, wherein the hydrate comprises between approximately 0.8 and 1.2 molar equivalents of water per mole of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid.
8. The hydrate of claim 7 that comprises between approximately 0.9 to 1.1 molar equivalents of water per mole of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid.
9. The hydrate of claim 7 that comprises between approximately 0.95 to 1.05 molar equivalents of water per mole of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid.
10. The hydrate of claim 7 that comprises between approximately 0.98 to 1.02 molar equivalents of water per mole of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid.
11. A pharmaceutical composition comprising the hydrate of claim 1 and a pharmaceutically acceptable carrier, excipient or adjuvant.
12. A hydrate of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid having an X-ray powder diffraction pattern characterized by FIG. 8 .
13. A hydrate of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, wherein the hydrate exhibits an X-ray powder diffraction pattern comprising peaks at approximately 6.89, 8.16, 11.13, 16.36, 17.52, 18.85, 20.77, 24.91 degrees 2θ.