Claims for Patent: 10,774,085

Summary for Patent: 10,774,085

Title:	Method of treatment using substituted pyrazolo[1,5-A] pyrimidine compounds
Abstract:	Compounds useful in the synthesis of compounds for treating pain, cancer, inflammation, neurodegenerative disease or Typanosoma cruzi infection in a mammal.
Inventor(s):	Haas; Julia (Boulder, CO), Andrews; Steven W. (Boulder, CO), Jiang; Yutong (Boulder, CO), Zhang; Gan (Stamford, CT)
Assignee:	ARRAY BIOPHARMA INC. (Boulder, CO)
Application Number:	16/044,653
Patent Claims:	1. A method for attenuating or ameliorating one or more symptoms of a cancer in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of a compound of Formula (I): ##STR00155## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is H or (1-6C alkyl); R.sup.2 is NR.sup.bR.sup.c; NR.sup.bR.sup.c forms a 5-membered heterocyclic ring optionally substituted with one or two substituents independently selected from OH and (1-4C)alkyl; Y is phenyl optionally substituted with one or more substituents independently selected from halogen, (1-4C)alkoxy, CF.sub.3 and CHF.sub.2; X is --CH.sub.2--; R.sup.3 is H or (1-4C alkyl); each R.sup.4 is independently selected from halogen, (1-4C)alkyl, OH, (1-4C)alkoxy, NH.sub.2, NH(1-4C alkyl) and CH.sub.2OH; and n is 0, 1, or 2, wherein the cancer exhibits one or more of overexpression, activation, amplification, and mutation of a Trk kinase. 2. The method of claim 1, wherein Y is phenyl optionally substituted with one or more halogen atoms. 3. The method of claim 2, wherein Y is phenyl optionally substituted with one or two fluorine atoms. 4. The method of claim 3, wherein R.sup.3 is hydrogen. 5. The method of claim 4, wherein R.sup.1 is hydrogen. 6. The method of claim 5, wherein the compound of Formula (I) is a trifluoroacetate salt, a sulfate salt or a hydrochloride salt. 7. The method of claim 5, wherein the compound of Formula (I) is a sulfate salt. 8. The method of claim 1, wherein the Trk kinase is TrkA. 9. The method of claim 1, wherein the Trk kinase is TrkB. 10. The method of claim 1, wherein the Trk kinase is TrkA and TrkB. 11. The method of claim 1, wherein the Trk kinase is selected from one or more of: TrkA, TrkB, and TrkC. 12. The method of claim 1, wherein the cancer exhibits overexpression of a Trk kinase. 13. The method of claim 1, wherein the cancer exhibits activation of a Trk kinase. 14. The method of claim 1, wherein the cancer exhibits amplification of a Trk kinase. 15. The method of claim 1, wherein the cancer exhibits mutation of a Trk kinase. 16. The method of claim 1, wherein the cancer is a hematological malignancy. 17. The method of claim 1, wherein the cancer is a solid tumor. 18. The method of claim 17, wherein the cancer is selected from the group consisting of a breast cancer, a lung cancer, a renal cancer, a thyroid cancer, an ovarian cancer, a prostate cancer, a pancreatic cancer, and a colorectal cancer. 19. The method of claim 1, wherein the cancer is selected from the group consisting of a neuroblastoma, a multiple myeloma, an astrocytoma, a medulloblastoma, a glioma, a melanoma, a thyroid carcinoma, a lung adenocarcinoma, a bone metastasis, and a large cell neuroendocrine tumor. 20. The method of claim 19, wherein the cancer is a lung adenocarcinoma. 21. The method of claim 1, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered orally. 22. The method of claim 1, wherein the method further comprises treating the mammal with a second therapy selected from the group consisting of surgery, radiotherapy, chemotherapy, a signal transduction inhibitor, or a monoclonal antibody. 23. The method of claim 1, wherein the method further comprises administering a second agent selected from the group consisting of a mitotic inhibitor, an alkylating agent, an anti-metabolite, an antisense DNA, an antisense RNA, an intercalating antibiotic, a growth factor inhibitor, a signal transduction inhibitor, a cell cycle inhibitor, an enzyme inhibitor, a retinoid receptor modulator, a proteasome inhibitor, a topoisomerase inhibitor, a biological response modifier, an anti-hormone, an angiogenesis inhibitor, a cytostatic agent, an anti-androgen, a targeted antibody, a HMG-CoA reductase inhibitor, and a prenyl-protein transferase inhibitor.