Cancer treatment agents containing optically active azabicyclo ring derivatives
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- SUMITOMO PHARMA CO LTD
- Filing Date
- 2026-03-09
- Publication Date
- 2026-06-16
AI Technical Summary
【0174】 本開示の技術は、本明細書で提供されるような用法用量で本開示の化合物を用いることにより、白血病、真性多血症、悪性リンパ腫、B細胞性リンパ腫、骨髄腫、脳腫瘍、頭頸部がん、食道がん、甲状腺がん、小細胞肺がん、非小細胞肺がん、乳がん、胃がん、胆のう·胆管がん、肝がん、肝細胞がん、膵がん、結腸がん、直腸がん、肛門がん、絨毛上皮がん、子宮体がん、子宮頸がん、卵巣がん、膀胱がん、尿路上皮がん、腎がん、腎細胞がん、前立腺がん、睾丸腫瘍、精巣胚細胞腫瘍、卵巣胚細胞腫瘍、ウイルムス腫瘍、悪性黒色腫、神経芽細胞腫、骨肉種、ユーイング肉腫、軟骨肉腫、軟部肉腫、又は皮膚がんの治療剤および/または予防剤として有用であり、特定の遺伝子変異を有するがんに対して優れた抗がん作用を示す。限定されるものではないが、本開示の技術を用いて、ヒトに対して忍容性が確認されたまたは期待される用量で投与し各種治療剤および/または予防剤として用いることができる。さらに、本化合物及び併用薬剤を用いることにより更に抗がん作用を増強させることができる。
Smart Images
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Abstract
Claims
1. A pharmaceutical product for treating or preventing cancer, comprising 5-fluoro-2-[(4-{7-[(1S,3S,4R)-5-methylidene-2-azabicyclo[2.2.2]octane-3-carbonyl]-2,7-diazaspiro[3.5]nonan-2-yl}pyrimidine-5-yl)oxy]-N,N-di(propan-2-yl)benzamide (hereinafter sometimes referred to as "free form") or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, characterized in that it is administered orally to the subject.
2. The pharmaceutical product according to claim 1, characterized in that it is administered orally once a day to the target of the pharmaceutical product.
3. The pharmaceutical product according to claim 1, characterized in that it is administered orally twice a day to the target of the pharmaceutical product.
4. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 40 mg when converted to a free form.
5. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 60 mg when converted to a free form.
6. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 80 mg when converted to a free form.
7. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 100 mg when converted to a free form.
8. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 120 mg when converted to a free form.
9. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 140 mg when converted to a free form.
10. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 180 mg when converted to a free form.
11. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 200 mg when converted to a free form.
12. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 220 mg when converted to a free form.
13. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 240 mg when converted to a free form.
14. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 260 mg when converted to a free form.
15. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 280 mg when converted to a free form.
16. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 300 mg when converted to a free form.
17. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 320 mg when converted to a free form.
18. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 340 mg when converted to a free form.
19. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 360 mg when converted to a free form.
20. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 380 mg when converted to a free form.
21. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 400 mg when converted to a free form.
22. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 500 mg when converted to a free form.
23. A pharmaceutical product according to any one of claims 1 to 3, wherein the single dose of the active ingredient is 600 mg when converted to a free form.
24. A pharmaceutical product according to any one of claims 1 to 23, used in combination with another drug or a pharmaceutically acceptable salt thereof, wherein the other drug is at least one selected from antitumor alkylating agents, antitumor antimetabolites, antitumor antibiotics, plant-derived antitumor agents, antitumor platinum coordination compounds, antitumor camptothecin derivatives, antitumor tyrosine kinase inhibitors, antitumor serine / threonine kinase inhibitors, antitumor phospholipid kinase inhibitors, antitumor monoclonal antibodies, interferons, biological response modifiers, hormone preparations, angiogenesis inhibitors, immune checkpoint inhibitors, epigenetics-related molecule inhibitors, protein post-translational modification inhibitors, proteasome inhibitors, and other antitumor agents.
25. A pharmaceutical product according to any one of claims 1 to 23, which is used in combination with another drug or a pharmaceutically acceptable salt thereof, wherein the other drug is (1) Venetoclax and azacitidine (2) Cytarabine and daunorubicin, and (3) Gilteritinib A pharmaceutical product, which is at least one of the following.
26. A pharmaceutical product according to any one of claims 1 to 23, administered once daily in combination with gilteritinib.
27. A pharmaceutical product according to any one of claims 1 to 23, administered in combination with 120 mg of gilteritinib.
28. A pharmaceutical product according to any one of claims 1 to 27, wherein the cancer is leukemia, polycythemia vera, malignant lymphoma, B-cell lymphoma, myeloma, brain tumor, head and neck cancer, esophageal cancer, thyroid cancer, small cell lung cancer, non-small cell lung cancer, breast cancer, stomach cancer, gallbladder and bile duct cancer, liver cancer, hepatocellular carcinoma, pancreatic cancer, colon cancer, rectal cancer, anal cancer, choriocarcinoma, endometrial cancer, cervical cancer, ovarian cancer, bladder cancer, urothelial carcinoma, kidney cancer, renal cell carcinoma, prostate cancer, testicular tumor, testicular germ cell tumor, ovarian germ cell tumor, Wilms' tumor, malignant melanoma, neuroblastoma, osteosarcoma, Ewing's sarcoma, chondrosarcoma, soft tissue sarcoma, or skin cancer.
29. A pharmaceutical product according to any one of claims 1 to 27, wherein the cancer is leukemia, B-cell lymphoma, neuroblastoma, or prostate cancer.
30. A pharmaceutical product according to any one of claims 1 to 27, wherein the cancer is leukemia.
31. The pharmaceutical product according to any one of claims 28 to 30, wherein the leukemia is acute leukemia, chronic lymphocytic leukemia, or chronic myeloid leukemia.
32. The pharmaceutical product according to claim 31, wherein the acute leukemia is MLL acute leukemia, MLL partial tandem overlap acute leukemia, or NPM1 mutation acute leukemia.
33. The pharmaceutical product according to claim 31, wherein the acute leukemia is MLL acute leukemia or NPM1 mutation acute leukemia.
34. The pharmaceutical product according to claim 31, wherein the acute leukemia is acute myeloid leukemia with MLL rearrangement.
35. The pharmaceutical product according to claim 31, wherein the acute leukemia is relapsed or refractory acute myeloid leukemia with MLL rearrangement.
36. The pharmaceutical product according to claim 31, wherein the acute leukemia is acute lymphoblastic leukemia with MLL rearrangement.
37. The pharmaceutical product according to claim 31, wherein the acute leukemia is relapsed or refractory acute lymphoblastic leukemia with MLL rearrangement.
38. The pharmaceutical product according to claim 31, wherein the acute leukemia is acute myeloid leukemia accompanied by an NPM1 mutation.
39. The pharmaceutical product according to claim 31, wherein the acute leukemia is relapsed or refractory acute myeloid leukemia accompanied by an NPM1 mutation.
40. The pharmaceutical product according to claim 31, wherein the acute leukemia is a leukemia accompanied by high expression of the HOXa gene group or the MEIS gene group.
41. A pharmaceutical product according to any one of claims 1 to 27, wherein the cancer is a tumor accompanied by a p53 gain-of-function mutation.
42. A pharmaceutical product according to any one of claims 1 to 27, wherein the cancer exhibits at least one genetic abnormality selected from NPM1 gene mutation, DNMT3A gene mutation, FLT gene mutation, and MLL translocation.
43. A pharmaceutical product according to any one of claims 1 to 27, wherein the cancer exhibits at least one genetic abnormality selected from NPM1 gene mutations, FLT gene mutations, and MLL translocations.
44. A pharmaceutical product according to any one of claims 1 to 27, wherein the cancer exhibits at least one genetic abnormality selected from NPM1 gene mutations and MLL translocations.
45. A pharmaceutical product according to any one of claims 1 to 44, administered to a subject having at least one genetic abnormality selected from NPM1 gene mutation, DNMT3A gene mutation, FLT gene mutation, and MLL translocation.
46. A pharmaceutical product according to any one of claims 1 to 44, administered to a subject having at least one genetic abnormality selected from NPM1 gene mutations and MLL translocations.
47. A pharmaceutical product according to any one of claims 1 to 44, administered to a subject having an NPM1 gene mutation.
48. Subjects with NPM1 gene mutations (1) A step of detecting NPM1 gene mutations in cancer cells obtained from the target, and (2) A step to determine whether or not the NPM1 gene mutation detected in step (1) is present. A pharmaceutical product according to claim 47, determined based on the above.
49. A pharmaceutical product according to any one of claims 1 to 44, administered to a subject having an MLL translocation.
50. MLL translocation thrombotic subjects (1) A step of detecting MLL translocations in cancer cells obtained from the target, and (2) A step to determine whether or not the MLL translocation detected in step (1) is present. A pharmaceutical product according to claim 49, determined based on the above.
51. A pharmaceutical product according to any one of claims 1 to 44, administered to a subject having an FLT gene mutation.
52. Subjects with FLT gene mutations (1) A step of detecting FLT gene mutations in cancer cells obtained from the target, and (2) A step to determine whether or not the FLT gene mutation detected in step (1) is present. A pharmaceutical product according to claim 51, determined based on the above.
53. A pharmaceutical product according to any one of claims 1 to 44, administered to a subject having a DNMT3A gene mutation.
54. Subjects with DNMT3A gene mutations (1) A step of detecting DNMT3A gene mutations in cancer cells obtained from the target, and (2) A step to determine whether or not the DNMT3A gene mutation detected in step (1) is present. A pharmaceutical product according to claim 53, determined based on the above.