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NZ762393B2 - Compounds and compositions for treating hematological disorders - Google Patents
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NZ762393B2 - Compounds and compositions for treating hematological disorders - Google Patents

Compounds and compositions for treating hematological disorders

Info

Publication number
NZ762393B2
NZ762393B2 NZ762393A NZ76239318A NZ762393B2 NZ 762393 B2 NZ762393 B2 NZ 762393B2 NZ 762393 A NZ762393 A NZ 762393A NZ 76239318 A NZ76239318 A NZ 76239318A NZ 762393 B2 NZ762393 B2 NZ 762393B2
Authority
NZ
New Zealand
Prior art keywords
cancer
leukemia
lymphoma
adenocarcinoma
tumor
Prior art date
Application number
NZ762393A
Other versions
NZ762393A (en
Inventor
Robert Booher
Original Assignee
Curis Inc
Filing date
Publication date
Application filed by Curis Inc filed Critical Curis Inc
Priority claimed from PCT/US2018/058194 external-priority patent/WO2019089580A1/en
Publication of NZ762393A publication Critical patent/NZ762393A/en
Publication of NZ762393B2 publication Critical patent/NZ762393B2/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/63Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06Antianaemics

Abstract

The present invention provides methods of treating hematological disorders and solid malignant tumors, using substituted indazole compounds and pharmaceutically acceptable salts thereof. The compounds inhibit IRAK4 and BCL-2 kinases.

Claims (23)

WE CLAIM:
1. Use of a compound in the manufacture of a medicament for the treatment of cancer in a subject undergoing treatment with venetoclax, wherein the compound is or a pharmaceutically acceptable salt thereof.
2. The use of claim 1, wherein the compound is a pharmaceutically acceptable salt of
3. The use of claim 1, wherein the compound is .
4. The use of any one of claims 1-3, wherein the cancer is diffuse large B-cell lymphoma (DLBCL) or Waldenstrom’s macroglobulinemia (WM).
5. The use of claim 4, wherein the DLBCL or WM is characterized by an L265P mutation in MYD88.
6. The use of claim 4, wherein the cancer is DLBCL.
7. The use of claim 6, wherein the DLBCL is the activated B-cell subtype DLBCL.
8. The use of claim 4, wherein the cancer is WM.
9. The use of any one of claims 1-3, wherein the cancer is a non-Hodgkin’s lymphoma.
10. The use of claim 9, wherein the non-Hodgkin’s lymphoma is selected from mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), CNS lymphoma, and testicular lymphoma.
11. The use of any one of claims 1-3, wherein the cancer is leukemia.
12. The use of claim 11, wherein the leukemia is acute myeloid leukemia (AML).
13. The use of claim 11, wherein the leukemia is acute lymphoblastic leukemia (ALL).
14. The use of claim 11, wherein the leukemia is chronic lymphocytic leukemia (CLL).
15. The use of claim 11, wherein the leukemia is chronic myelogenous leukemia (CML).
16. The use of claim 11, wherein the leukemia is a myelodysplastic syndrome.
17. The use of claim 16, wherein the myelodysplastic syndrome is selected from refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia.
18. The use of any one of claims 1-3, wherein the cancer is a myeloproliferative neoplasm.
19. The use of claim 18, wherein the myeloproliferative neoplasm is selected from chronic myelogenous leukemia (CML), chronic neutrophilic leukemia (CNL), polycythemia vera (PCV), primary myelofibrosis, essential thrombocythemia, chronic eosinophilic leukemia, and mastocytosis.
20. The use of any one of claims 1-3, wherein the cancer is a solid malignant tumor.
21. The use of claim 20, wherein the solid malignant tumor is selected from biliary cancer, cholangiocarcinoma, bladder cancer, breast cancer, adenocarcinoma of the breast, papillary carcinoma of the breast, mammary cancer, medullary carcinoma of the breast, brain cancer, meningioma, glioma, astrocytoma, oligodendroglioma, glioblastoma, medulloblastoma, cervical cancer, cervical adenocarcinoma, colorectal cancer, colon cancer, rectal cancer, colorectal adenocarcinoma, gastric cancer, stomach adenocarcinoma, gastrointestinal stromal tumor (GIST), head and neck cancer, head and neck squamous cell carcinoma, oral cancer, oral squamous cell carcinoma (OSCC), kidney cancer, nephroblastoma, Wilms' tumor, renal cell carcinoma, liver cancer, hepatocellular cancer (HCC), malignant hepatoma, lung cancer, bronchogenic carcinoma, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), adenocarcinoma of the lung, neuroblastoma, neurofibroma, neurofibromatosis (NF) type 1 or type 2, schwannomatosis, neuroendocrine cancer, gastroenteropancreatic neuroendocrine tumor (GEP-NET), carcinoid tumor, osteosarcoma, ovarian cancer, cystadenocarcinoma, ovarian embryonal carcinoma, ovarian adenocarcinoma, pancreatic cancer, pancreatic adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), prostate cancer, prostate adenocarcinoma, skin cancer, squamous cell carcinoma (SCC), keratoacanthoma (A), melanoma, basal cell carcinoma (BCC), malignant fibrous histiocytoma (MFH), liposarcoma, malignant peripheral nerve sheath tumor (MPNST), chondrosarcoma, fibrosarcoma, myxosarcoma, and osteosarcoma.
22. The use of claim 20, wherein the solid malignant tumor is breast cancer or pancreatic cancer.
23. The use of any one of claims 1-22 substantially as herein described with reference to any one or more of the examples but excluding comparative examples.
NZ762393A 2018-10-30 Compounds and compositions for treating hematological disorders NZ762393B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201762579502P 2017-10-31 2017-10-31
PCT/US2018/058194 WO2019089580A1 (en) 2017-10-31 2018-10-30 Compounds and compositions for treating hematological disorders

Publications (2)

Publication Number Publication Date
NZ762393A NZ762393A (en) 2025-07-25
NZ762393B2 true NZ762393B2 (en) 2025-10-29

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