TYK2 inhibitors, uses, and methods for production thereof
The present invention provides compounds of formula I useful as inhibitors of Tyrosine Kinase 2 (Tyk2) solid forms and compositions thereof, methods of producing the same, and methods of using the same in the treatment of Tyk2-mediated diseases.
1. A method for inhibiting non-receptor tyrosine protein kinase 2 (Tyk2) in a patient in need thereof, comprising administering to the patient a compound of Formula I:
or a pharmaceutically acceptable salt thereof,
wherein the patient suffers from a Tyk2-mediated disorder and the Tyk2-mediated disorder is selected from:
a) an autoimmune disorder selected from ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, systemic sclerosis, psoriasis, Crohn's disease, and ulcerative colitis;
b) an inflammatory disorder selected from psoriatic arthritis, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, psoriasis, and inflammatory bowel disease;
c) T-cell acute lymphoblastic leukemia (T-ALL);
d) an endocrine disorder selected from polycystic ovary syndrome, Crouzon's syndrome, and type 1 diabetes;
e) Alzheimer's disease; or
f) a disorder associated with transplantation selected from transplant rejection and graft versus host disease;
wherein each of X, Y, and Z is independently hydrogen or deuterium.
2. The method of claim 1 , wherein the disorder is an autoimmune disorder selected from ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, systemic sclerosis, psoriasis, Crohn's disease, and ulcerative colitis.
3. The method of claim 1 , wherein the disorder is an inflammatory disorder selected from rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, and inflammatory bowel disease.
4. The method of claim 1 , wherein the disorder is T-cell acute lymphoblastic leukemia (T-ALL).
5. The method of claim 4 , wherein the T-cell acute lymphoblastic leukemia is associated with one or more activating mutations in TYK2.
6. The method of claim 1 , wherein the disorder is a disorder associated with transplantation selected from transplant rejection and graft versus host disease.
7. The method of claim 1 , wherein the disorder is an endocrine disorder selected from polycystic ovary syndrome, Crouzon's syndrome, and type 1 diabetes.
8. The method of claim 1 , wherein the disorder is Alzheimer's disease.
9. A method of treating a Tyk2-mediated disorder comprising administering to a patient in need thereof a compound of Formula I:
or a pharmaceutically acceptable salt thereof,
wherein the patient suffers from a Tyk2-mediated disorder and the Tyk2-mediated disorder is selected from:
a) an autoimmune disorder selected from ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Crohn's disease, and ulcerative colitis; or
b) an inflammatory disorder selected from psoriatic arthritis and inflammatory bowel disease;
wherein each of X, Y, and Z is independently hydrogen or deuterium.
10. The method of claim 9 , wherein the disorder is ankylosing spondylitis.
11. The method of claim 9 , wherein the disorder is systemic lupus erythematosus.
12. The method of claim 9 , wherein the disorder is psoriasis.
13. The method of claim 9 , wherein the disorder is Crohn's disease.
14. The method of claim 9 , wherein the disorder is ulcerative colitis.
15. The method of claim 9 , wherein the disorder is psoriatic arthritis.
16. The method of claim 9 , wherein the disorder is inflammatory bowel disease.
17. A method of treating a Tyk2-mediated disorder comprising administering to a patient in need thereof a compound of Formula I:
or a pharmaceutically acceptable salt thereof,
wherein the Tyk2-mediated disorder is T-cell acute lymphoblastic leukemia (T-ALL);
wherein each of X, Y, and Z is independently hydrogen or deuterium.
18. The method of claim 17 , wherein the T-cell acute lymphoblastic leukemia is associated with one or more activating mutations in TYK2.