ME02663B - Derivati benzimidazola kao inhibitori pi3 kinaze - Google Patents
Derivati benzimidazola kao inhibitori pi3 kinazeInfo
- Publication number
- ME02663B ME02663B MEP-2017-59A MEP5917A ME02663B ME 02663 B ME02663 B ME 02663B ME P5917 A MEP5917 A ME P5917A ME 02663 B ME02663 B ME 02663B
- Authority
- ME
- Montenegro
- Prior art keywords
- cancer
- leukemia
- cell
- lymphoma
- pharmaceutically acceptable
- Prior art date
Links
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title 1
- 150000001556 benzimidazoles Chemical class 0.000 title 1
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims 12
- 150000001875 compounds Chemical class 0.000 claims 10
- 206010028980 Neoplasm Diseases 0.000 claims 9
- 208000032839 leukemia Diseases 0.000 claims 8
- 208000008770 Multiple Hamartoma Syndrome Diseases 0.000 claims 6
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims 6
- 206010060862 Prostate cancer Diseases 0.000 claims 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 6
- 201000011510 cancer Diseases 0.000 claims 5
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- 206010006187 Breast cancer Diseases 0.000 claims 4
- 208000026310 Breast neoplasm Diseases 0.000 claims 4
- 201000002847 Cowden syndrome Diseases 0.000 claims 4
- 206010014733 Endometrial cancer Diseases 0.000 claims 4
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 4
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 claims 4
- 206010018338 Glioma Diseases 0.000 claims 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 4
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 4
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 claims 4
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 claims 4
- 206010038389 Renal cancer Diseases 0.000 claims 4
- 208000035269 cancer or benign tumor Diseases 0.000 claims 4
- 210000004027 cell Anatomy 0.000 claims 4
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 claims 4
- 201000010536 head and neck cancer Diseases 0.000 claims 4
- 208000014829 head and neck neoplasm Diseases 0.000 claims 4
- 201000010982 kidney cancer Diseases 0.000 claims 4
- 208000014018 liver neoplasm Diseases 0.000 claims 4
- 201000001441 melanoma Diseases 0.000 claims 4
- XTKLTGBKIDQGQL-UHFFFAOYSA-N 2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylbenzimidazole-4-carboxylic acid Chemical compound CC1=NC2=C(C(O)=O)C=C(N3CCOCC3)C=C2N1CC1=CC=CC(C(F)(F)F)=C1C XTKLTGBKIDQGQL-UHFFFAOYSA-N 0.000 claims 3
- 206010009944 Colon cancer Diseases 0.000 claims 3
- 208000032612 Glial tumor Diseases 0.000 claims 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 3
- 210000001744 T-lymphocyte Anatomy 0.000 claims 3
- 230000007812 deficiency Effects 0.000 claims 3
- 206010017758 gastric cancer Diseases 0.000 claims 3
- 201000011549 stomach cancer Diseases 0.000 claims 3
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 2
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 claims 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 2
- 201000007815 Bannayan-Riley-Ruvalcaba syndrome Diseases 0.000 claims 2
- 206010005003 Bladder cancer Diseases 0.000 claims 2
- 208000011691 Burkitt lymphomas Diseases 0.000 claims 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 2
- 208000012609 Cowden disease Diseases 0.000 claims 2
- 206010014967 Ependymoma Diseases 0.000 claims 2
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 claims 2
- 208000036566 Erythroleukaemia Diseases 0.000 claims 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 2
- 208000006168 Ewing Sarcoma Diseases 0.000 claims 2
- 208000002966 Giant Cell Tumor of Bone Diseases 0.000 claims 2
- 208000017604 Hodgkin disease Diseases 0.000 claims 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims 2
- 206010062904 Hormone-refractory prostate cancer Diseases 0.000 claims 2
- 208000005726 Inflammatory Breast Neoplasms Diseases 0.000 claims 2
- 206010021980 Inflammatory carcinoma of the breast Diseases 0.000 claims 2
- 208000022010 Lhermitte-Duclos disease Diseases 0.000 claims 2
- 206010061523 Lip and/or oral cavity cancer Diseases 0.000 claims 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 2
- 206010025323 Lymphomas Diseases 0.000 claims 2
- 208000000172 Medulloblastoma Diseases 0.000 claims 2
- 208000035490 Megakaryoblastic Acute Leukemia Diseases 0.000 claims 2
- 206010027406 Mesothelioma Diseases 0.000 claims 2
- 208000003445 Mouth Neoplasms Diseases 0.000 claims 2
- 208000034578 Multiple myelomas Diseases 0.000 claims 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims 2
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 claims 2
- 206010061306 Nasopharyngeal cancer Diseases 0.000 claims 2
- 206010029260 Neuroblastoma Diseases 0.000 claims 2
- 208000033755 Neutrophilic Chronic Leukemia Diseases 0.000 claims 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 2
- 206010033128 Ovarian cancer Diseases 0.000 claims 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 2
- 208000007452 Plasmacytoma Diseases 0.000 claims 2
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 claims 2
- 206010061934 Salivary gland cancer Diseases 0.000 claims 2
- 206010039491 Sarcoma Diseases 0.000 claims 2
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 claims 2
- 208000024313 Testicular Neoplasms Diseases 0.000 claims 2
- 206010057644 Testis cancer Diseases 0.000 claims 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 2
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 2
- 206010047741 Vulval cancer Diseases 0.000 claims 2
- 208000004354 Vulvar Neoplasms Diseases 0.000 claims 2
- 208000008383 Wilms tumor Diseases 0.000 claims 2
- 208000021841 acute erythroid leukemia Diseases 0.000 claims 2
- 208000013593 acute megakaryoblastic leukemia Diseases 0.000 claims 2
- 208000020700 acute megakaryocytic leukemia Diseases 0.000 claims 2
- 201000011143 bone giant cell tumor Diseases 0.000 claims 2
- 210000004556 brain Anatomy 0.000 claims 2
- 201000010881 cervical cancer Diseases 0.000 claims 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 2
- 201000010903 chronic neutrophilic leukemia Diseases 0.000 claims 2
- 201000004101 esophageal cancer Diseases 0.000 claims 2
- 201000003444 follicular lymphoma Diseases 0.000 claims 2
- 208000005017 glioblastoma Diseases 0.000 claims 2
- 201000009277 hairy cell leukemia Diseases 0.000 claims 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 2
- 201000004653 inflammatory breast carcinoma Diseases 0.000 claims 2
- 201000007270 liver cancer Diseases 0.000 claims 2
- 201000005202 lung cancer Diseases 0.000 claims 2
- 208000020816 lung neoplasm Diseases 0.000 claims 2
- 201000011649 lymphoblastic lymphoma Diseases 0.000 claims 2
- 208000003747 lymphoid leukemia Diseases 0.000 claims 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 2
- 201000008968 osteosarcoma Diseases 0.000 claims 2
- 201000002528 pancreatic cancer Diseases 0.000 claims 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims 2
- 206010041823 squamous cell carcinoma Diseases 0.000 claims 2
- 201000003120 testicular cancer Diseases 0.000 claims 2
- 201000002510 thyroid cancer Diseases 0.000 claims 2
- 206010044412 transitional cell carcinoma Diseases 0.000 claims 2
- 208000022679 triple-negative breast carcinoma Diseases 0.000 claims 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims 2
- 201000005102 vulva cancer Diseases 0.000 claims 2
- 201000003741 Gastrointestinal carcinoma Diseases 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 239000007983 Tris buffer Substances 0.000 claims 1
- 229940034982 antineoplastic agent Drugs 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 210000001072 colon Anatomy 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 201000002313 intestinal cancer Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 210000002784 stomach Anatomy 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic 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
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/10—Radicals substituted by halogen atoms or nitro radicals
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
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- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
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- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
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- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
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- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (14)
1.Jedinjenje formule (Ia) koje je 2-metil-1-{[2-metil-3-(trifluorometil)fenil]metil}-6-(4-morfolinil) 1H-benzimidazol-4-karboksilna kiselina, ili njegova farmaceutski prihvatljiva so.
2.Jedinjenje prema zahtevu 1 formule (Ia) koje je 2-metil-1-{[2-metil-3-(trifluorometil)fenil]metil}-6-(4-morfolinil) 1H-benzimidazol-4-karboksilna kiselina.
3.Farmaceutski prihvatljiva so jedinjenja formule (Ia) prema zahtevu 1.
4.Farmaceutski prihvatljiva so jedinjenja formule (Ia) prema zahtevu 3, gde je so 1 : 1 tris so.
5.Farmaceutska kompozicija koja sadrži jedinjenje formule (Ia) ili njegovu farmaceutski prihvatljivu so prema bilo kom od zahteva 1-4 i farmaceutski prihvatljiv nosač.
6.Farmaceutska kompozicija prema zahtevu 5 za upotrebu u lečenju osetljive neoplazme kod sisara kojima je to potrebno.
7.Jedinjenje formule (Ia) ili njegova farmaceutski prihvatljiva so prema bilo kom od zahteva 1-4 za upotrebu u terapiji.
8.Kombinacija (a) 2-metil-1-{[2-metil-3-(trifluorometil)fenil]metil}-6-(4-morfolinil)-1H-benzimidazol- 4-karboksilne kiseline ili njene farmaceutski prihvatljive soli i (b) bar jednog anti-neoplastičnog sredstva; za upotrebu u lečenju kancera.
9.Jedinjenje formule (Ia) ili njegove farmaceutski prihvatljive soli prema bilo kom od zahteva 1-4, ili farmaceutske kompozicije prema zahtevu 5, ili kombinacije prema zahtevu 8, za upotrebu u lečenju osetljive neoplazme na nedostatak PTEN izabrane između moždanih (glioma), glioblastoma, leukemija, Bannayan-Zonana-ovog sindroma, Cowden-ove bolesti, Lhermitte-Duclos-ove bolesti, kancera grudi, zapaljenskog kancera grudi, kolorektalnog kancera, Wilm-ovog tumora, Ewing-ov sarkoma, rabdomiosarkoma, ependimoma, meduloblastoma, kancera creva, kancera glave i vrata, kancera bubrega, kancera pluća, kancera jetre, melanoma, karcinoma skvamoznih ćelija, kancera jajnika, kancera pankreasa, kancera prostate, sarkoma, kancera, osteosarkoma, tumora gigantskih ćelija kosti, kancera tiroidee, limfoblasne leukemije t-ćelija, hronične mijeloidne leukemije, hronične limfocitne leukemije, leukemije dlakavih ćelija, akutne leukemija limfoblasta, akutne mijeloidne leukemije, hronične leukemije neutrofila, akutne limfoblastne leukemije T ćelija, plazmacitoma, leukemije imunoblastnih velikih ćelija, leukemije mantle ćelija, višestrukog mijeloma, leukemije megakarioblasta, akutne megakariocitne leukemije, promijelocitne leukemije, eritroleukemija, malignog limfoma, hodžkinovog limfoma, nehodžkinovog limfoma, limfoblastičnog limfoma T ćelija, Burkit-ovog limfoma, folikularnog limfoma, neuroblastoma, kancera bešike, urotelijalnog kancera, kancera vulve, cervikalnog kancera, kancera endometrijuma, kancera bubrega, mezotelioma, kancera jednjaka, kancera pljuvačnih žlezda, hepatocelularnog kancera, kancera želudca, kancera nazofaringsa, bukalnog kancerkancer usta, GIST (gastrointestinalnog stromalnog tumora), i kancera testisa.
10.Jedinjenje formule (Ia) ili njegova farmaceutski prihvatljiva so za upotrebu, ili farmaceutska kompozicija za upotrebu, ili kombinacija za upotrebu, prema zahtevu 9, gde neoplazma u vezi sa nedostatkom PTEN je izabrana između kancera prostate kancera nemalih ćelija pluća, kancera endometrijuma, kancera želudca, melanoma, kancera glave i vrata, kancera grudi, uključujući trostuko negativni kancer grudi i gliom.
11.Jedinjenje formule (Ia) ili njegove farmaceutski prihvatljive soli za upotrebu, ili farmaceutska kompozicija za upotrebu, ili kombinacija za upotrebu, prema zahtevu 10, gde pomenuti kancer prostate je hormonski refraktorni kancer prostate.
12.Upotreba jedinjenja formule (Ia), ili njegove farmaceutski prihvatljive soli, prema bilo kom od zahteva 1-4 u proizvodnji leka za upotrebu u lečenju PTEN izabrane između moždanih (glioma), glioblastoma, leukemija, Bannayan-Zonana-ovog sindroma, Cowden-ove bolesti, Lhermitte-Duclos-ove bolesti, kancera grudi, zapaljenskog kancera grudi, kolorektalnog kancera, Wilm-ovog tumora, Ewing-ov sarkoma, rabdomiosarkoma, ependimoma, meduloblastoma, kancera creva, kancera glave i vrata, kancera bubrega, kancera pluća, kancera jetre, melanoma, karcinoma skvamoznih ćelija, kancera jajnika, kancera pankreasa, kancera prostate, sarkoma, kancera, osteosarkoma, tumora gigantskih ćelija kosti, kancera tiroidee, limfoblasne leukemije t-ćelija, hronične mijeloidne leukemije, hronične limfocitne leukemije, leukemije dlakavih ćelija, akutne leukemija limfoblasta, akutne mijeloidne leukemije, hronične leukemije neutrofila, akutne limfoblastne leukemije T ćelija, plazmacitoma, leukemije imunoblastnih velikih ćelija, leukemije mantle ćelija, višestrukog mijeloma, leukemije megakarioblasta, akutne megakariocitne leukemije, promijelocitne leukemije, eritroleukemija, malignog limfoma, hodžkinovog limfoma, nehodžkinovog limfoma, limfoblastičnog limfoma T ćelija, Burkit-ovog limfoma, folikularnog limfoma, neuroblastoma, kancera bešike, urotelijalnog kancera, kancera vulve, cervikalnog kancera, kancera endometrijuma, kancera bubrega, mezotelioma, kancera jednjaka, kancera pljuvačnih žlezda, hepatocelularnog kancera, kancera želudca, kancera nazofaringsa, bukalnog kancerkancer usta, GIST (gastrointestinalnog stromalnog tumora), i kancera testisa.
13.Upotreba prema zahtevu 12, gde pomenuta osetljiva neoplazma na nedostatak PTEN je izabrana između kancera prostate kancera nemalih ćelija pluća, kancera endometrijuma, kancera želudca, melanoma, kancera glave i vrata, kancera grudi, uključujući trostuko negativni kancer grudi i gliom.
14. Upotreba prema zahtevu 13, gde je kancer prostate hormonski refraktorni kancer prostate.
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| EP11831214.9A EP2624696B1 (en) | 2010-10-06 | 2011-09-23 | Benzimidazole derivatives as pi3 kinase inhibitors |
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