Polymorphic compounds and uses thereof
The present invention relates to compounds and methods useful for selectively modulating mTORC1 activity.
1. A method of treating a disease, disorder, or condition selected from depression, treatment-resistant depression, a lysosomal storage disorder, juvenile neuronal ceroid lipofuscinosis (JNCL), cystinosis, Fabry disease, mucolipidosis type IV (MLIV), mental retardation or a genetic form of autism in a patient in need thereof,
comprising administering to the patient in need thereof an effective amount of a crystalline form of compound A:
or composition thereof, wherein the crystalline form is selected from the group consisting of Form A of compound A, Form B of compound A, and Form C of compound A; and wherein:
Form A of compound A is characterized by peaks in its XRPD pattern at about 4.4, about 16.2, about 17.3, about 17.5, and about 17.7 degrees 2-theta;
Form B of compound A is characterized by peaks in its XRPD pattern at about 5.0, about 6.2, about 15.2, about 17.5, and about 17.8 degrees 2-theta; and
Form C of compound A is characterized by peaks in its XRPD pattern at about 7.0, about 16.1, about 16.3, about 19.3, and about 19.5 degrees 2-theta.
2. The method of claim 1 , wherein said crystalline form is Form A of compound A having at least about 95% by weight of Form A of compound A.
3. The method of claim 1 , wherein said crystalline form is Form A of compound A having at least about 99% by weight of Form A of compound A.
4. The method of claim 1 , wherein said crystalline form is Form A of compound A.
5. The method of claim 1 , wherein said crystalline form is Form A of compound A having the XRPD pattern as depicted in FIG. 1 wherein each peak is within +/−0.2 degrees 2-theta.
6. The method of claim 1 , wherein said crystalline form is Form B of compound A.
7. The method of claim 1 , wherein said crystalline form is Form B of compound A having the XRPD pattern as depicted in FIG. 4 wherein each peak is within +/−0.2 degrees 2-theta.
8. The method of claim 1 , wherein said crystalline form is Form C of compound A.
9. The method of claim 1 , wherein said crystalline form is Form C of compound A having the XRPD pattern as depicted in FIG. 7 wherein each peak is within +/−0.2 degrees 2-theta.
10. The method of claim 1 , wherein said crystalline form is Form B of compound A having at least about 95% by weight of Form B of compound A.
11. The method of claim 1 , wherein said crystalline form is Form B of compound A having at least about 99% by weight of Form B of compound A.
12. The method of claim 1 , wherein said crystalline form is Form C of compound A having at least about 95% by weight of Form C of compound A.
13. The method of claim 1 , wherein said crystalline form is Form C of compound A having at least about 99% by weight of Form C of compound A.
14. The method of claim 1 , wherein the composition comprising the crystalline form of compound A further comprises a pharmaceutically acceptable carrier or excipient.
15. The method of claim 14 , wherein the crystalline form is Form A of compound A.
16. The method of claim 14 , wherein the crystalline form is Form B of compound A.
17. The method of claim 14 , wherein the crystalline form is Form C of compound A.
18. The method of claim 1 , wherein the disease, disorder, or condition is treatment-resistant depression.
19. A method of treating treatment-resistant depression in a patient in need thereof, comprising administering to the patient in need thereof an effective amount of a crystalline form of compound A:
or composition thereof, wherein the crystalline form is Form A of compound A; and wherein:
Form A of compound A is characterized by peaks in its XRPD pattern at about 4.4, about 16.2, about 17.3, about 17.5, and about 17.7 degrees 2-theta.
20. The method of claim 19 , having at least about 95% by weight of Form A of compound A.