ISOTOPOLOGUES OF 5-AZACYTIDINE
The present disclosure provides pharmaceutical compositions comprising cytidine analogs for oral administration, wherein the compositions release the cytidine analog substantially in the stomach. Also provided are methods of treating diseases and disorders using the oral formulations provided herein.
1 - 74 . (canceled)
75 . A compound of the formula:
or a pharmaceutically acceptable salt or solvate thereof, wherein:
at least one of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 is a hydrogen isotopically enriched with deuterium, and the others of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 are non-enriched hydrogen atoms.
76 . The compound of claim 75 , wherein one of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 is a hydrogen isotopically enriched with deuterium, and the others of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 are non-enriched hydrogen atoms.
77 . The compound of claim 75 , wherein two of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 are hydrogens isotopically enriched with deuterium, and the others of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 are non-enriched hydrogen atoms.
78 . The compound of claim 75 , wherein three of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 are hydrogens isotopically enriched with deuterium, and the others of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 are non-enriched hydrogen atoms.
79 . The compound of claim 75 , wherein four of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 are hydrogens isotopically enriched with deuterium, and the others of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 are non-enriched hydrogen atoms.
80 . The compound of claim 75 , wherein five of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 are hydrogens isotopically enriched with deuterium, and the others of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 are non-enriched hydrogen atoms.
81 . The compound of claim 75 , wherein six of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 are hydrogens isotopically enriched with deuterium, and the other of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 is a non-enriched hydrogen atoms.
82 . The compound of claim 75 , wherein seven of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , and Y 7 are hydrogens isotopically enriched with deuterium.
83 . The compound of claim 75 , wherein Y 1 is a hydrogen isotopically enriched with deuterium.
84 . The compound of claim 75 , wherein Y 2 is a hydrogen isotopically enriched with deuterium.
85 . The compound of claim 75 , wherein Y 3 is a hydrogen isotopically enriched with deuterium.
86 . The compound of claim 75 , wherein Y 4 is a hydrogen isotopically enriched with deuterium.
87 . The compound of claim 75 , wherein Y 5 is a hydrogen isotopically enriched with deuterium.
88 . The compound of claim 75 , wherein Y 6 is a hydrogen isotopically enriched with deuterium.
89 . The compound of claim 75 , wherein Y 7 is a hydrogen isotopically enriched with deuterium.
90 . A pharmaceutical composition comprising the compound of claim 75 , or a pharmaceutically acceptable salt or solvate thereof.
91 . The composition of claim 90 , wherein the composition is a tablet comprising a non-enteric coating.
92 . A method for treating diseases associated with abnormal cell proliferation, comprising administering to a patient a compound of claim 75 , or a pharmaceutically acceptable salt or solvate thereof.
93 . The method of claim 92 , wherein the compound is administered orally.
94 . The method of claim 92 , wherein the method further comprises co-administrating to the patient an additional therapeutic agent.
95 . The method of claim 92 , wherein the disease associated with abnormal cell proliferation is myelodysplastic syndromes.
96 . The method of claim 92 , wherein the disease associated with abnormal cell proliferation is acute myelogenous leukemia.