HRP20230161T1 - Aza-heterobiciklički inhibitori za mat2a i postupci uporabe za liječenje raka - Google Patents
Aza-heterobiciklički inhibitori za mat2a i postupci uporabe za liječenje raka Download PDFInfo
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- HRP20230161T1 HRP20230161T1 HRP20230161TT HRP20230161T HRP20230161T1 HR P20230161 T1 HRP20230161 T1 HR P20230161T1 HR P20230161T T HRP20230161T T HR P20230161TT HR P20230161 T HRP20230161 T HR P20230161T HR P20230161 T1 HRP20230161 T1 HR P20230161T1
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- 206010028980 Neoplasm Diseases 0.000 title claims 9
- 201000011510 cancer Diseases 0.000 title claims 9
- 238000000034 method Methods 0.000 title claims 3
- 239000003112 inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 16
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 16
- 125000001072 heteroaryl group Chemical group 0.000 claims 15
- 229910052760 oxygen Inorganic materials 0.000 claims 12
- 229910052717 sulfur Inorganic materials 0.000 claims 12
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 9
- 229910052736 halogen Inorganic materials 0.000 claims 9
- 150000003839 salts Chemical class 0.000 claims 7
- 150000002367 halogens Chemical class 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 4
- -1 benzoisothiazolyl Chemical group 0.000 claims 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims 3
- 201000009030 Carcinoma Diseases 0.000 claims 3
- 206010025323 Lymphomas Diseases 0.000 claims 3
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 125000005843 halogen group Chemical group 0.000 claims 3
- 201000001441 melanoma Diseases 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- 125000001424 substituent group Chemical group 0.000 claims 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims 2
- 208000025324 B-cell acute lymphoblastic leukemia 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
- 206010005003 Bladder cancer Diseases 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 2
- 101000947881 Homo sapiens S-adenosylmethionine synthase isoform type-2 Proteins 0.000 claims 2
- 208000031671 Large B-Cell Diffuse Lymphoma 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
- 206010027406 Mesothelioma Diseases 0.000 claims 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 2
- 102100035947 S-adenosylmethionine synthase isoform type-2 Human genes 0.000 claims 2
- 102100034187 S-methyl-5'-thioadenosine phosphorylase Human genes 0.000 claims 2
- 101710136206 S-methyl-5'-thioadenosine phosphorylase Proteins 0.000 claims 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 2
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 2
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims 2
- 201000004101 esophageal cancer Diseases 0.000 claims 2
- 206010017758 gastric cancer Diseases 0.000 claims 2
- 201000010536 head and neck cancer Diseases 0.000 claims 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- 201000005202 lung cancer Diseases 0.000 claims 2
- 208000020816 lung neoplasm Diseases 0.000 claims 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 2
- 208000015768 polyposis Diseases 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 2
- 208000000587 small cell lung carcinoma Diseases 0.000 claims 2
- 201000011549 stomach cancer Diseases 0.000 claims 2
- 208000022679 triple-negative breast carcinoma Diseases 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 claims 1
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 claims 1
- 206010003571 Astrocytoma Diseases 0.000 claims 1
- 206010004146 Basal cell carcinoma Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010006417 Bronchial carcinoma Diseases 0.000 claims 1
- 208000011691 Burkitt lymphomas Diseases 0.000 claims 1
- 208000005243 Chondrosarcoma Diseases 0.000 claims 1
- 208000006332 Choriocarcinoma Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 206010010356 Congenital anomaly Diseases 0.000 claims 1
- 208000009798 Craniopharyngioma Diseases 0.000 claims 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 1
- 206010014733 Endometrial cancer Diseases 0.000 claims 1
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 1
- 208000006168 Ewing Sarcoma Diseases 0.000 claims 1
- 201000008808 Fibrosarcoma Diseases 0.000 claims 1
- 208000032612 Glial tumor Diseases 0.000 claims 1
- 206010018338 Glioma Diseases 0.000 claims 1
- 208000017604 Hodgkin disease Diseases 0.000 claims 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims 1
- 206010021042 Hypopharyngeal cancer Diseases 0.000 claims 1
- 206010056305 Hypopharyngeal neoplasm Diseases 0.000 claims 1
- 206010023825 Laryngeal cancer Diseases 0.000 claims 1
- 206010062038 Lip neoplasm Diseases 0.000 claims 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims 1
- 208000037196 Medullary thyroid carcinoma Diseases 0.000 claims 1
- 208000000172 Medulloblastoma Diseases 0.000 claims 1
- 208000034578 Multiple myelomas Diseases 0.000 claims 1
- 208000005927 Myosarcoma Diseases 0.000 claims 1
- 206010029260 Neuroblastoma Diseases 0.000 claims 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010033701 Papillary thyroid cancer Diseases 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 208000007452 Plasmacytoma Diseases 0.000 claims 1
- 208000037276 Primitive Peripheral Neuroectodermal Tumors Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000015634 Rectal Neoplasms Diseases 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- 208000006265 Renal cell carcinoma Diseases 0.000 claims 1
- 201000000582 Retinoblastoma Diseases 0.000 claims 1
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 claims 1
- 206010061934 Salivary gland cancer Diseases 0.000 claims 1
- 201000010208 Seminoma Diseases 0.000 claims 1
- 206010041067 Small cell lung cancer Diseases 0.000 claims 1
- 206010043276 Teratoma Diseases 0.000 claims 1
- 206010062129 Tongue neoplasm Diseases 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 208000006593 Urologic Neoplasms Diseases 0.000 claims 1
- 208000009956 adenocarcinoma Diseases 0.000 claims 1
- 201000006966 adult T-cell leukemia Diseases 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 201000001531 bladder carcinoma Diseases 0.000 claims 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 claims 1
- 125000004452 carbocyclyl group Chemical group 0.000 claims 1
- 208000019065 cervical carcinoma Diseases 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 229910052805 deuterium Inorganic materials 0.000 claims 1
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 201000003914 endometrial carcinoma Diseases 0.000 claims 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 claims 1
- 201000007487 gallbladder carcinoma Diseases 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 1
- 201000006866 hypopharynx cancer Diseases 0.000 claims 1
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 1
- 125000000842 isoxazolyl group Chemical group 0.000 claims 1
- 206010023841 laryngeal neoplasm Diseases 0.000 claims 1
- 201000006721 lip cancer Diseases 0.000 claims 1
- 206010024627 liposarcoma Diseases 0.000 claims 1
- 201000005249 lung adenocarcinoma Diseases 0.000 claims 1
- 201000005243 lung squamous cell carcinoma Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 claims 1
- 206010027191 meningioma Diseases 0.000 claims 1
- 201000002077 muscle cancer Diseases 0.000 claims 1
- 201000008968 osteosarcoma Diseases 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 201000001514 prostate carcinoma Diseases 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 125000002098 pyridazinyl group Chemical group 0.000 claims 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims 1
- 206010038038 rectal cancer Diseases 0.000 claims 1
- 201000001275 rectum cancer Diseases 0.000 claims 1
- 201000010174 renal carcinoma Diseases 0.000 claims 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims 1
- 230000002381 testicular Effects 0.000 claims 1
- 208000013818 thyroid gland medullary carcinoma Diseases 0.000 claims 1
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 claims 1
- 201000006134 tongue cancer Diseases 0.000 claims 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61K31/495—Heterocyclic 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/20—Spiro-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Claims (14)
1. Spoj, naznačen time, da je predstavljen Formulom I:
[image]
u kojoj
L je O, S, NR, ili veza;
R je H ili C1-C6-alkil;
R1 se bira iz skupine koju čine C1-C6-alkil, C2-C6-alkenil, C3-C6-karbociklil, -(C1-C6-alkil)(C3-C6-karbociklil), i -(C1-C6-alkil)(C3-C6-cikloalkenil), pri čemu
bilo koji alkil u R1 je ravan ili razgranat, i
R1 je opcionalno supstituiran s jednim do šest halogena ili s jednim do šest deuterija;
ili kada L je NR, tada R i R1 u kombinaciji s L predstavljaju 3-člani do 6-člani heterocikloalkil (gdje su 1-4 člana prstena neovisno odabrani od N, O i S) opcionalno supstituiran s jednim ili više RA;
R2 i R3 se neovisno biraju iz skupine koju čine (C2-C6)alkinil, C6-C10-aril, C3-C6-karbociklil, 5-člani do 10-člani heteroaril (gdje su 1-4 člana heteroarila neovisno odabrani od N, O i S), i 3-člani do 14-člani heterocikloalkil (gdje su 1-4 člana heterocikloalkila neovisno odabrani od N, O i S),
pri čemu su R2 i R3 neovisno i opcionalno supstituirani s jednim ili više supstituenata odabranih iz skupine koju čine RA, ORA, halogen, -N=N-RA, -NRARB, -(C1-C6-alkil)NRARB, -C(O)ORA, -C(O)NRARB, -OC(O)RA, -Si(C1-C6-alkil)3, i -CN;
R4 se bira iz skupine koju čine H, C1-C6-alkil (opcionalno supstituiran s jednim ili više halogena, hidroksi ili 3-članih do 14-članih heterocikloalkoksi (gdje su 1-4 člana heterocikloalkoksi neovisno odabrani od N, O i S)), -O(C1-C6-alkil) (opcionalno supstituiran s jednim ili više halogena), -OH, halogen, -CN, -(C1-C6-alkil)NRARB, i -NRARB;
R5 se bira iz skupine koju čine H, C1-C6-alkil, C1-C6-alkoksi, C2-C6-alkenil, C2-C6-alkinil, halogen, -CN, i -NRCRD;
RA i RB se neovisno biraju iz skupine koju čine H, -CN, -hidroksi, okso, C1-C6-alkil, C1-C6-alkoksi, C2-C6-alkenil, C2-C6-alkinil, -NH2, -S(O)0-2-(C1-C6-alkil), -S(O)0-2-(C6-C10-aril), -C(O)(C1-C6-alkil), -C(O)(C3-C14-karbociklil), -C3-C14-karbociklil, -(C1-C6-alkil)(C3-C14-karbociklil), C6-C10-aril, 3-člani do 14-člani heterocikloalkil, i (C1-C6-alkil)-(3-člani do 14-člani heterocikloalkil) (gdje su 1-4 člana heterocikloalkila neovisno odabrani od N, O i S), i 5-člani do 10-člani heteroaril (gdje su 1-4 člana heteroarila neovisno odabrani od N, O i S);
pri čemu je svaki ostatak skupine alkil, alkoksi, alkenil, alkinil, aril, karbociklil, heterocikloalkil, i heteroaril od RA i RB, opcionalno supstituiran s jednim ili više supstituenata odabranih iz skupine koju čine deuterij, hidroksi, halogen, -NR'2 (gdje se svaki R' neovisno bira iz skupine koju čine C1-C6-alkil, C2-C6-alkenil, C2-C6-alkinil, C6-C10-aril, 3-člani do 14-člani heterocikloalkil i -(C1-C6-alkil)-(3-člani do 14-člani heterocikloalkil) (gdje su 1-4 člana prstena neovisno odabrani od N, O i S), i 5-člani do 10-člani heteroaril (gdje su 1-4 člana heteroarila neovisno odabrani od N, O i S), -NHC(O)(OC1-C6-alkil), -NO2, -CN, okso, -C(O)OH, -C(O)O(C1-C6-alkil), -C1-C6-alkil(C1-C6-alkoksi), -C(O)NH2, C1-C6-alkil, -C(O)C1-C6-alkil, -OC1-C6-alkil, -Si(C1-C6-alkil)3, -S(O)0-2-(C1-C6-alkil), C6-C10-aril, -(C1-C6-alkil)(C6-C10-aril), 3-člani do 14-člani heterocikloalkil, i -(C1-C6-alkil)-(3-člani do 14-člani heterocikl)(gdje su 1-4 člana heterocikla neovisno odabrani od N, O i S), i -O(C6-C14-aril), pri čemu je svaki alkil, alkenil, aril i heterocikloalkil supstituent u RA i RB opcionalno supstituiran s jednim ili više supstituenata odabranih iz skupine koju čine hidroksi, -OC1-C6-alkil, halogen, -NH2, -(C1-C6-alkil)NH2, -C(O)OH, CN i okso;
svaki od RC i RD se neovisno bira od H i C1-C6-alkila;
ili njegova farmaceutski prihvatljiva sol.
2. Spoj prema patentnom zahtjevu 1, naznačen time, da:
R4 se bira iz skupine koju čine H, C1-C6-alkil (opcionalno supstituiran s jednim ili više halogena, hidroksi ili 3-članih do 14-članih heterocikloalkoksi (pri čemu se 1-4 člana heterocikloalkoksi neovisno biraju od N, O i S)), -O(C1-C6-alkil), -(C1-C6-alkil)NRARB, i -NRARB (gdje se RA i RB neovisno biraju od H i C1-C6-alkila); i
R5 se bira iz skupine koju čine H, C1-C6-alkil, C1-C6-alkoksi, i -NRCRD.
3. Spoj prema patentnom zahtjevu 1 ili 2, naznačen time, da:
(a) barem jedan od R4 i R5 je H; i/ili
(b) R4 je H; i/ili
(c) R5 je H; i/ili
(d) svaki od R4 i R5 je H.
4. Spoj prema bilo kojem od patentnih zahtjeva 1 do 3, naznačen time, da R2 je opcionalno supstituirani C6-C10-aril ili opcionalno supstituirani 5-člani do 10-člani heteroaril, opcionalno gdje R2 je:
(a) opcionalno supstituirani C6-C10-aril,
opcionalno, gdje R2 je opcionalno supstituirani fenil; ili
(b) opcionalno supstituirani 5-člani do 10-člani heteroaril, i pri čemu jedan član prstena je N, dok opcionalno pritom:
(i) R2 je opcionalno supstituirani 5-člani do 6-člani heteroaril; i/ili
(ii) R2 je opcionalno supstituirani 6-člani heteroaril; i/ili
(iii) R2 je opcionalno supstituirani piridil.
5. Spoj prema bilo kojem od patentnih zahtjeva 1 do 4, naznačen time, da R3 je:
(a) opcionalno supstituirani 3-člani do 14-člani heterocikloalkil ili opcionalno supstituirani 5-člani do 10-člani heteroaril,
opcionalno, gdje se R3 bira iz skupine koju čine benzotiazolil, benzoizotiazolil, benzoksazolil, piridinil, piridinonil, piridazinil, benzimidazolil, benzotriazolil, indazolil, kvinoksalinil, kvinolinil, kvinazolinil, imidazopiridinil, pirazolopiridinil, triazolopiridinil, kinolinil, izoksazolil, pirazolil, benzofuranil, dihidrobenzofuranil, dihidrobenzodioksinil, i tetrahidrobenzodioksinil, od kojih svaki može biti opcionalno supstituiran; ili
(b) opcionalno supstituirani C6-C10-aril,
gdje opcionalno, R3 je opcionalno supstituirani fenil.
6. Spoj prema bilo kojem od patentnih zahtjeva 1 do 3, naznačen time, da R2 je opcionalno supstituirani fenil i R3 je opcionalno supstituirani 3-člani do 14-člani heterocikloalkil ili opcionalno supstituirani 5-člani do 10-člani heteroaril.
7. Spoj prema bilo kojem od patentnih zahtjeva 1 do 6, naznačen time, da L je O ili NR, opcionalno gdje R1 je:
(a) opcionalno supstituirani C1-C6-alkil ili opcionalno supstituirani C3-C6-karbociklil; i/ili
(b) C1-C3-alkil koji je opcionalno supstituiran s jednim do tri F.
8. Spoj prema patentnom zahtjevu 1, naznačen time, da
L je O ili NR, i R je H;
R1 je C1-C3-alkil koji je opcionalno supstituiran s jednim do tri F.
R2 je opcionalno supstituirani 3-člani do 14-člani heterocikloalkil ili opcionalno supstituirani 5-člani do 10-člani heteroaril (pri čemu jedan član heterocikloalkila ili heteroarila jest N) ili opcionalno supstituirani C6-C10-aril;
R3 je opcionalno supstituirani 3-člani do 14-člani heterocikloalkil ili opcionalno supstituirani 5-člani do 10-člani heteroaril, gdje su 1 do 3 člana heterocikloalkila ili heteroarila neovisno odabrani od N, O, S; i
svaki od R4 i R5 je H,
opcionalno gdje L je NR.
9. Spoj prema patentnom zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time, da se spoj bira iz sljedeće tablice:
[image]
[image]
(nastavak)
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(nastavak)
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(nastavak)
[image]
(nastavak)
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(nastavak)
[image]
(nastavak)
[image]
(nastavak)
[image]
(nastavak)
[image]
.
10. Farmaceutski pripravak, naznačen time, da sadrži terapijski učinkovitu količinu spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 9 ili njegove farmaceutski prihvatljive soli, te farmaceutski prihvatljiv nosač.
11. Inhibicijski spoj za MAT2A ili njegova farmaceutski prihvatljiva sol prema bilo kojem od patentnih zahtjeva 1 do 9, naznačen time, da je za uporabu u postupku liječenja raka kod pojedinca koji pati od istoga, pri čemu postupak obuhvaća davanje pojedincu učinkovite količine inhibicijskog spoja za MAT2A ili njegove farmaceutski prihvatljive soli u skladu s bilo kojim od patentnih zahtjeva 1 do 9.
12. Spoj za uporabu prema patentnom zahtjevu 11, naznačen time, da se kod raka radi o raku kojemu je uklonjen MTAP.
13. Spoj prema bilo kojem od patentnih zahtjeva 1 do 9, ili njegova farmaceutski prihvatljiva sol, naznačen time, da je za uporabu u liječenju raka kod pojedinca koji pati od istoga.
14. Spoj za uporabu prema patentnom zahtjevu 13, ili njegova farmaceutski prihvatljiva sol, naznačen time, da rak je:
(a) rak s uklonjenim MTAP; i/ili
(b) odabran iz skupine koju čine mezoteliom, neuroblastom, karcinom rektuma, karcinom debelog crijeva, adenomatozni polipozni obiteljski karcinom i urođeni nepolipozni kolorektalni rak, karcinom jednjaka, karcinom usana, karcinom grkljana, karcinom donjeg dijela ždrijela, karcinom jezika, karcinom žlijezde slinovnice, rak želuca, adenokarcinom, medularni tiroidni karcinom, papilarni tiroidni karcinom, bubrežni karcinom, parenhimski karcinom bubrega, karcinom jajnika, karcinom cerviksa, karcinom tijela maternice, karcinom endometrija, korionski karcinom, karcinom gušterače, karcinom prostate, karcinom mokraćnog mjehura, karcinom testisa, karcinom dojke, karcinom mokraćnog trakta, melanom, tumori mozga, limfom, rak glave i vrata, akutna limfatska leukemija (ALL), kronična limfatska leukemija (CLL), akutna mijeloična leukemija (AML), kronična mijeloična leukemija (CML), hepatocelularni karcinom, karcinom žučnog mjehura, bronhijalni karcinom, karcinom malih stanica pluća, karcinom ne-malih stanica pluća, multipli mijelom, bazaliom, teratom, retinoblastom, koroidni melanom, seminom, rabdomiosarkom, osteosarkom, hondrosarkom, miosarkom, liposarkom, fibrosarkom, Ewingov sarkom, i plazmacitom; i/ili
(c) odabran iz skupine koju čine akutna limfocitna leukemija B-stanica (B-ALL), mezoteliom, limfom, karcinom gušterače, rak pluća, rak želuca, rak jednjaka, karcinom mokraćnog mjehura, rak mozga, rak glave i vrata, melanom, i rak dojke,
opcionalno pritom rak je:
(i) rak pluća odabran iz skupine koju čine rak ne-malih stanica pluća, rak malih stanica pluća, adenokarcinom pluća, i karcinom rožnatih stanica pluća; ili
(ii) trostruko negativni rak dojke (TNBC); ili
(iii) tumor mozga odabran iz skupine koju čine gliom, glioblastom, astrocitom, meningiom, meduloblastom, periferni neuroektodermalni tumori, i kraniofaringiom; ili
(iv) limfom odabran iz skupine koju čine limfom plaštenih stanica, Hodgkinov limfom, ne-Hodgkinov limfom, Burkittov limfom, difuzni limfom velikih B-stanica (DLBCL), i leukemija/limfom T-stanica kod odraslih.
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| EP19845796.2A EP3902803B1 (en) | 2018-12-27 | 2019-12-27 | Aza-heterobicyclic inhibitors of mat2a and methods of use for treating cancer |
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| SG11202105469YA (en) | 2018-12-10 | 2021-06-29 | Ideaya Biosciences Inc | 2-oxoquinazoline derivatives as methionine adenosyltransferase 2a inhibitors |
| KR20230094196A (ko) * | 2020-07-31 | 2023-06-27 | 탱고 테라퓨틱스, 인크. | Mtap-결핍 및/또는 mta 축적 암의 치료에 유용한 피페리딘-1-일-n-피리딘-3-일-2-옥소아세트아마이드 유도체 |
| WO2022052924A1 (zh) * | 2020-09-11 | 2022-03-17 | 上海凌达生物医药有限公司 | 一类含氮稠环类化合物的制备方法和用途 |
| WO2022206730A1 (zh) * | 2021-03-29 | 2022-10-06 | 武汉人福创新药物研发中心有限公司 | 嘧啶并吡嗪酮化合物及其用途 |
| WO2022253242A1 (zh) * | 2021-06-02 | 2022-12-08 | 南京正大天晴制药有限公司 | 蛋氨酸腺苷转移酶2a抑制剂 |
| US20230192679A1 (en) * | 2021-12-17 | 2023-06-22 | Tango Therapeutics, Inc. | Crystalline forms, pharmaceutical compositions and methods of use thereof |
| WO2023116696A1 (zh) * | 2021-12-21 | 2023-06-29 | 南京正大天晴制药有限公司 | 蛋氨酸腺苷转移酶2a的杂环抑制剂 |
| TW202342024A (zh) * | 2022-03-11 | 2023-11-01 | 大陸商賽諾哈勃藥業（成都）有限公司 | 甲硫胺酸腺苷轉移酶抑制劑、其藥物組合物及應用 |
| WO2024080788A1 (ko) | 2022-10-13 | 2024-04-18 | 한미약품 주식회사 | 신규한 트리사이클 유도체 화합물 및 이의 용도 |
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| PE20200342A1 (es) | 2017-05-22 | 2020-02-14 | Janssen Pharmaceuticals Inc | Derivados de indolina sustituidos como inhibidores de la replicacion virica de dengue |
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