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 pharmaceutical composition comprising 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 and a pharmaceutically acceptable carrier, excipient or adjuvant, wherein the hydrate exhibits an X-ray powder diffraction pattern comprising a peak at approximately 8.2 degrees 2θ, and the composition is for oral administration.
2. The pharmaceutical composition of claim 1 , wherein the hydrate exhibits an X-ray powder diffraction pattern further comprising peaks at approximately 6.9, 11.1 and 18.8 degrees 2θ.
3. The pharmaceutical composition of claim 2 , wherein the hydrate exhibits an X-ray powder diffraction pattern further comprising peaks at approximately 16.4, 17.5, 20.8 and 24.9 degrees 2θ.
4. The pharmaceutical composition of claim 2 , wherein the hydrate has an X-ray powder diffraction pattern substantially similar to FIG. 8 .
5. A pharmaceutical composition comprising 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 and a pharmaceutically acceptable carrier, excipient or adjuvant, 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, and wherein the composition is for oral administration.
6. The pharmaceutical composition of claim 5 , wherein the hydrate 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.
7. The pharmaceutical composition of claim 5 , wherein the hydrate 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.
8. The pharmaceutical composition of claim 5 , wherein the hydrate 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.