Isotopologues of 2-(tert-butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide
Provided herein are isotopologues of Compound A, which are enriched with isotopes such as, for example, deuterium. Pharmaceutical compositions comprising the isotope-enriched compounds, and methods of using such compounds are also provided.
1. A method for treating a disease selected from a group consisting of systemic sclerosis, scleroderma, chronic allograft nephropathy, antibody mediated rejection, and lupus, comprising administering to a subject having the disease an effective amount of a compound having the following structure:
or a pharmaceutically acceptable salt, stereoisomer or solvate thereof,
wherein one or more of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 , Y 9 , Y 10 , Y 11 , Y 12 , Y 13 , Y 14 , Y 15 , Y 16 , Y 17 , Y 18 , Y 19 , Y 20 , Y 21 and Y 22 is a hydrogen that is isotopically enriched with deuterium, and the others of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 , Y 9 , Y 10 , Y 11 , Y 12 , Y 13 , Y 14 , Y 15 , Y 16 , Y 17 , Y 18 , Y 19 , Y 20 , Y 21 and Y 22 are non-enriched hydrogen atoms.
2. The method of claim 1 , wherein the compound has the following structure:
3. The method of claim 1 , wherein one of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 , Y 9 , Y 10 , Y 11 , Y 12 , Y 13 , Y 14 , Y 15 , Y 16 , Y 17 , Y 18 , Y 19 , Y 20 , Y 21 and Y 22 is isotopically enriched with deuterium, and the others are non-enriched hydrogens.
4. The method of claim 1 , wherein two of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 , Y 9 , Y 10 , Y 11 , Y 12 , Y 13 , Y 14 , Y 15 , Y 16 , Y 17 , Y 18 , Y 19 , Y 20 , Y 21 and Y 22 are isotopically enriched with deuterium, and the others are non-enriched hydrogens.
5. The method of claim 1 , wherein the compound is:
6. The method of claim 1 , wherein the compound is:
7. The method of claim 1 , wherein the compound at a concentration of 10 μM inhibits JNK1 by at least about 50%.
8. The method of claim 1 , wherein the disease is systemic sclerosis.
9. The method of claim 1 , wherein the disease is scleroderma.
10. The method of claim 1 , wherein the disease is chronic allograft nephropathy.
11. The method of claim 1 , wherein the disease is antibody mediated rejection.
12. The method of claim 1 , wherein the disease is lupus.