Cocrystal forms of ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo [2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl) methyl sulfamate, formulations and uses thereof
The present invention is directed to cocrystal forms of ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxcyclopentyl) methyl sulfamate of formula (I). The invention is also directed to methods of making cocrystal forms of ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl) methyl sulfamate of formula (I). The invention is also directed to the pharmaceutical use of a cocrystal form as an E1 activating enzyme inhibitor, as well as a pharmaceutical composition comprising a cocrystal form. The invention is further directed to a method of treatment comprising administering a cocrystal form of ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo [2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate of formula (I).
1. A cocrystal of ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate of formula (I) and a coformer:
wherein the coformer is selected from the group consisting of acetic acid, benzoic acid, camphoric acid, caproic acid, trans-cinnamic acid, ethylenediamine, fumaric acid, gentisic acid, D-glucuronic acid, glycolic acid, hippuric acid, DL-lactic acid, L-lysine, L-malic acid, malonic acid, DL-mandelic acid, meglumine, orotic acid, oxalic acid, piperazine, L-proline, L-pyroglutamic acid, saccharin, succinic acid, and vanillin.
2. The cocrystal of claim 1 , wherein the coformer is glycolic acid.
3. The cocrystal of claim 2 which is an anhydrous mono-glycolic acid cocrystal.
4. The cocrystal of claim 3 , characterized by an XRPD pattern having peaks at 2θ angles of 8.94°±0.2°, 18.48°±0.2°, and 20.41°±0.2°.
5. The cocrystal of claim 3 , characterized by an endothermic peak at about 138.1° C., as determined by differential scanning calorimetry.
6. The cocrystal of claim 3 , characterized by an about 5.3 wt % loss between about 101° C. and about 175° C. and a weight loss at about 216° C., as determined by thermal gravimetric analysis.
7. The cocrystal of claim 1 , wherein the coformer is hippuric acid.
8. The cocrystal of claim 7 which is an anhydrous mono-hippuric acid cocrystal.
9. The cocrystal of claim 8 , characterized by an XRPD pattern having peaks at 2θ angles of 4.05°±0.2°, 19.25°±0.2°, and 22.60°±0.2°.
10. The cocrystal of claim 8 , characterized by an endothermic peak at about 150.9° C., as determined by differential scanning calorimetry.
11. The cocrystal of claim 8 , characterized by a weight loss at about 235° C., as determined by thermal gravimetric analysis.
12. The cocrystal of claim 1 , wherein the coformer is saccharin.
13. The cocrystal of claim 12 which is an anhydrous mono-saccharin cocrystal.
14. The cocrystal of claim 13 , characterized by an XRPD pattern having peaks at 2θ angles of 7.86°±0.2°, 15.81°±0.2°, and 17.97°±0.2°.
15. The cocrystal of claim 13 , characterized by an endothermic peak at about 198.5° C. overlapping with an exothermic peak at about 201.8° C., as determined by differential scanning calorimetry.
16. The cocrystal of claim 13 , characterized by an about 1.9 wt % loss between about 171° C. and about 200° C., as determined by thermal gravimetric analysis.
17. The cocrystal of claim 1 , wherein the coformer is malonic acid.
18. The cocrystal of claim 17 which is an anhydrous mono-malonic acid cocrystal.
19. The cocrystal of claim 18 , characterized by an XRPD pattern having peaks at 2θ angles of 3.66°±0.2°, 19.24°±0.2°, and 25.14°±0.2°.
20. The cocrystal of claim 18 , characterized by an endothermic peak at about 155.1° C., as determined by differential scanning calorimetry.
21. The cocrystal of claim 18 , characterized by an about 14.0 wt % loss between about 135° C. and about 184° C., as determined by thermal gravimetric analysis.
22. A pharmaceutical composition comprising any one of the cocrystals of claim 1 , and pharmaceutically acceptable carrier or diluent.