HRP20221412T1 - Spojevi koji inhibiraju mcl-1 protein - Google Patents
Spojevi koji inhibiraju mcl-1 protein Download PDFInfo
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- HRP20221412T1 HRP20221412T1 HRP20221412TT HRP20221412T HRP20221412T1 HR P20221412 T1 HRP20221412 T1 HR P20221412T1 HR P20221412T T HRP20221412T T HR P20221412TT HR P20221412 T HRP20221412 T HR P20221412T HR P20221412 T1 HRP20221412 T1 HR P20221412T1
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- 150000001875 compounds Chemical class 0.000 title claims 52
- 101001056180 Homo sapiens Induced myeloid leukemia cell differentiation protein Mcl-1 Proteins 0.000 title 1
- 102100026539 Induced myeloid leukemia cell differentiation protein Mcl-1 Human genes 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims 58
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 22
- 125000001072 heteroaryl group Chemical group 0.000 claims 12
- 125000005843 halogen group Chemical group 0.000 claims 11
- 125000002950 monocyclic group Chemical group 0.000 claims 11
- 229910003827 NRaRb Inorganic materials 0.000 claims 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims 8
- 229910052760 oxygen Inorganic materials 0.000 claims 8
- 125000003118 aryl group Chemical group 0.000 claims 7
- 125000005842 heteroatom Chemical group 0.000 claims 7
- 229910052757 nitrogen Inorganic materials 0.000 claims 7
- 125000006580 bicyclic heterocycloalkyl group Chemical group 0.000 claims 6
- 125000001424 substituent group Chemical group 0.000 claims 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 5
- -1 C1-6alkylhalo Chemical group 0.000 claims 5
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 5
- 239000003085 diluting agent Substances 0.000 claims 5
- 239000003937 drug carrier Substances 0.000 claims 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims 5
- 229910052717 sulfur Inorganic materials 0.000 claims 5
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 4
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 3
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 2
- 208000034578 Multiple myelomas Diseases 0.000 claims 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- 125000004434 sulfur atom Chemical group 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 206010066476 Haematological malignancy Diseases 0.000 claims 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 claims 1
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- 208000000453 Skin Neoplasms Diseases 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 201000000050 myeloid neoplasm Diseases 0.000 claims 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 201000000849 skin cancer Diseases 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (39)
1. Spoj s Formulom I':
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ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera,
naznačen time što:
Z je C ili N;
Q je O ili S;
W je CRWARWB ili C=O;
RWA i RWB su neovisno odabrani od H, C1-3alkila, halo, -OH, ili -O-C1-3alkila;
b, predstavljen simbolom
[image]
je jednostruka ili dvostruka kemijska veza koja može biti cis ili trans;
R1 je neovisno odabran od H, halo, C1-6alkilhalo, C1-6alkila, -(CH2CH2O)nRa, - SO2Ra, -C(=O)Ra ,-C(=O)ORa, ili -C(=O)NRaRb;
R2 je odabran od H, halo, -C1-6haloalkila, -C1-6alkila, -O-C1-6alkila, -C2-6alkenila, -C1-6alkil-O-C1-6alkila, -(CH2CH2O)nRa, -SO2Ra, -C(=O)Ra , -C(=O)ORa, -OC(=O)Ra, ili -C(=O)NRaRb,
R3 je neovisno odabran od H, -C1-6alkilhalo, -C1-6alkila, -C2-6 alkenila, - (CH2CH2O)nRa, -C(=O)Ra ,-C(=O)ORa, ili -C(=O)NRaRb;
svaki od R4, R5, R6, R7, i R8 je neovisno odabran iz niza koji sadrži H, halo, -C1-6haloalkil, -C1-6alkil, -O-C1-6alkil, -C2-6alkenil, -C1-6alkil-O-C1-6alkil, -(CH2CH2O)nRa, -SO2Ra, -C(=O)Ra ,-C(=O)ORa, -OC(=O)Ra, -C(=O)NRaRb, 6- do 12-člani aril ili heteroaril, 5- do 12-člani spirocikloalkil ili spiroheterocikloalkil, 3- do 12-člani cikloalkenil, 3- do 12-člani monociklički ili biciklički cikloalkil, ili 3- do 12-članu monocikličku ili bicikličku heterocikloalkilnu skupinu, pri čemu heteroarilna, spiroheterocikloalkilna i heterocikloalkilna skupina imaju 1, 2, 3, ili 4 heteroatoma neovisno odabrana između O, N ili S, pri čemu cikloalkilna, spirocikloalkilna, spiroheterocikloalkilna, i heterocikloalkilna skupina mogu uključivati C=O skupinu, i dalje pri čemu spiroheterocikloalkilne i heterocikloalkilne skupine mogu uključivati S=O ili SO2;
alternativno R3 i R4 zajedno s atomima na koje su vezani mogu tvoriti 5- do 12-člani prsten, po izboru sadržavajući heteroatom odabran između N, O ili S atoma, uz S i N atome prisutne u prstenu, pri čemu prsten može po izboru sadržavati najmanje jednu dvostruku vezu; i prsten može biti supstituiran s 0, 1, 2 ili 3 supstituenta R3A;
R3A je neovisno odabran od H, halo, -OH, C1-6haloalkila, C1-6alkila, O-C1-6alkila, C2-6alkenila, -C1-6alkil-O-C1-6alkila, -(CH2CH2O)nRa, -SO2Ra, -C(=O)Ra ,-C(=O)ORa, -OC(=O)Ra, - C(=O)NRaRb;
svaki od R4A, R5A, R6A, R7A, i R8A je neovisno odabran od H, OH, halo, ili -C1-6alkila;
R7A i R8A su odsutni kada je b dvostruka kemijska veza;
R9 je neovisno odabran iz niza koji sadrži H, -C1-6haloalkil, -C1-6alkil, -C2-6alkenil, -C2-6alkinil, - (CH2CH2O)nRa, -C(=O)Ra ,-C(=O)ORa, -C(=O)NRaRb, -C1-6alkil-O-C1-6alkil, 6- do 12-člani aril ili heteroaril, 5- do 12-člani spirocikloalkil ili spiroheterocikloalkil, 3- do 12-člani cikloalkenil, 3- do 12-člani monociklički ili biciklički cikloalkil, ili 3- do 12-člana monociklička ili biciklička heterocikloalkilna skupina, pri čemu heteroarilne, spiroheterocikloalkilne i heterocikloalkilne skupine imaju 1, 2, 3 ili 4 heteroatoma neovisno odabrana između O, N ili S, pri čemu cikloalkilne, spirocikloalkilne, spiroheterocikloalkilne i heterocikloalkilne skupine mogu uključivati C=O skupinu, i dalje pri čemu spiroheterocikloalkilne i heterocikloalkilne skupine mogu uključivati S=O ili SO2;
R9A je neovisno odabran od -N=N=N,
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pri čemu je -C1-6alkil bilo kojeg od supstituenata R1, R2, R3, R4, R5, R6, R7, R8, R9, R4A, R5A, R6A, R7A, i R8A nesupstituiran ili supstituiran s 1, 2 ili 3 supstituenta R12 neovisno odabran iz niza koji čine OH, -OC1-6alkil, -C1-6alkil-O-C1-6alkil, halo, -O-haloC1-6alkil, -CN, -NRaRb, - (NRaRbRc)n, -SO2Ra, -(CH2CH2O)nCH3, (=O), -C(=O), -C(=O)Ra, -OC(=O)Ra, -C(=O)ORa, - C(=O)NRaRb, -O-SiRaRbRc, -O-(3- do 12-člani heterocikloakil), fenil, 6- do 12-člani aril ili heteroaril, 5- do 12-člani spirocikloalkil ili spiroheterocikloalkil, 3- do 12-člani cikloalkenil, 3- do 12-člani monociklički ili biciklički cikloalkil, ili 3- do 12-člana monociklička ili biciklička heterocikloalkilna skupina pri čemu heteroarilne, spiroheterocikloalkilne i heterocikloalkilne skupine imaju 1, 2, 3 ili 4 heteroatoma neovisno odabrana između O, N ili S, pri čemu cikloalkilna, spirocikloalkilna, spiroheterocikloalkilna, i heterocikloalkilna skupina mogu uključivati C=O skupinu, i dalje pri čemu spiroheterocikloalkilne i heterocikloalkilne skupine mogu uključivati S=O ili SO2;
pri čemu arilna, heteroarilna, cikloalkilna, heterocikloalkilna, spirocikloalkilna i spiroheterocikloalkilna skupina za bilo koji od supstituenata R2, R4, R5, R6, R7, R8, R9, i R12 može biti nesupstituirana ili supstituirana s 1, 2, 3 ili 4 supstituenata R13 neovisno odabrana iz niza koji sadrži OH, halo, -C1-6alkil, -OC1-6alkil, - C1-6alkil-OH, - C1-6alkil-O-C1-6alkil, C1-6haloalkil, -O-haloC1-6alkil, -SO2Rc, -NRcRd, -CN, -C(=O)NRcRd, - C(=O)Rc, -OC(=O)Ra, -C(=O)ORc, -B(OH)2, 6- do 12-člani aril ili heteroaril, 5- do 12-člani spirocikloalkil ili spiroheterocikloalkil, 3- do 12-člani cikloalkenil, 3- do 12-člani monociklički ili biciklički cikloalkil, ili 3- do 12-članu monocikličku ili bicikličku heterocikloalkilnu skupinu, pri čemu heteroarilna, spiroheterocikloalkilna, i heterocikloalkilna skupine imaju 1, 2, 3, ili 4 heteroatoma neovisno odabrana između O, N ili S, pri čemu cikloalkilna, spirocikloalkilna, spiroheterocikloalkilna, i heterocikloalkilna skupina mogu uključivati C=O skupinu , i dalje pri čemu spiroheterocikloalkilne i heterocikloalkilne skupine mogu uključivati S=O ili SO2;
pri čemu svaki Ra, Rb, Rc, i Rd je neovisno H, OH, -C1-6alkil, -C1-6alkenil, -C2-6alkinil, -C1-6alkil-NR14R14, NR14R14, -SO2R14, -(CH2CH2O)nCH3, (=O), -C(=O)R14, -OC(=O)R14, - C(=O)OR14, -C(=O)NR14R14, C1-6haloalkil, -O-haloC1-6alkil, -C1-6alkil-O-C1-6alkil, -C1-6alkil-OH, benzil, fenil, -C1-6alkil-3- do 12-člani heterocikloalkil, 6- do 12-člani aril ili heteroaril, 5- do 12-člani spirocikloalkil ili spiroheterocikloalkil, 3- do 12-člani cikloalkenil, 3- do 12-člani monociklički ili biciklički cikloalkil, ili 3- do 12-članu monocikličku ili bicikličku heterocikloalkilnu skupinu, pri čemu heteroarilne, spiroheterocikloalkilne i heterocikloalkilne skupine i heterocikloalkilna skupina -C1-6alkil-heterocikloalkilne skupine imaju 1, 2, 3, ili 4 heteroatoma neovisno odabrana između O, N ili S, pri čemu su cikloalkilna, spirocikloalkilna, spiroheterocikloalkilna, heterocikloalkilna i heterocikloalkilna skupina - C1-6alkil-heterocikloalkilne skupine može uključivati C=O skupinu, i dalje pri čemu spiroheterocikloalkilne i heterocikloalkilne skupine mogu uključivati S=O ili SO2;
alkil, aril, heteroaril, spirocikloalkil, spiroheterocikloalkil, cikloalkil, heterocikloalkil i heterocikloalkilne skupine -C1-6alkil-heterocikloalkilnih skupina od Ra, Rb, Rc, i Rd mogu biti nesupstituirane ili supstituirane s 1, 2, 3, ili 4 supstituenata R14 neovisno odabrana iz niza koji sadrži H, OH, -N=N=N, halo, -C1-6alkil, -OC1-6alkil, C1-6haloalkil, -O-haloC1-6alkil, fenil, tolil, -C(O)C1-6alkil, -C(O)OCH3, SO2-fenil, ili -SO2-N(CH3)2; i
n je neovisno, u svakom slučaju, cijeli broj od 1, 2, 3 ili 4.
2. Spoj prema zahtjevu 1, naznačen time što spoj s Formulom I' ima Formulu I'a:
[image]
ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera.
3. Spoj prema zahtjevu 1, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što je b dvostruka veza.
4. Spoj prema zahtjevu 1, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što Z je C.
5. Spoj prema zahtjevu 1, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što Q je O.
6. Spoj prema zahtjevu 1, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što W je CRWARWB i RWA i RWB su oba H.
7. Spoj prema zahtjevu 1, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što R1 je halo.
8. Spoj prema zahtjevu 7, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što R1 je CI.
9. Spoj prema zahtjevu 1, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što R2 je H i R3 je H.
10. Spoj prema zahtjevu 1, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što je R4 odabran od H, -C1-6alkila, -C1-6alkilhalo, -C1-6alkil-O-C1-6alkila, ili -(CH2CH2O)nRa, pri čemu - C1-6alkil je nesupstituiran ili supstituiran s -OH, (=O), fenil, -O-SiRaRbRc, -NRaRb, 3- do 12-člani cikloalkil, ili 3- do 12-člani monociklički ili biciklički heterocikloalkil koji ima 1, 2, 3, ili 4 heteroatoma neovisno odabranih između O, N ili S.
11. Spoj prema zahtjevu 10, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što R4 je H ili -C1-6alkil.
12. Spoj prema zahtjevu 1, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što R5 je H ili -C1-6 alkil.
13. Spoj prema zahtjevu 1, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što R6 je H ili -C1-6 alkil.
14. Spoj prema zahtjevu 1, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što svaki od R4A, R5A, R6A, R7A i R8A je neovisno odabran od H, OH, halo, ili -C1-6alkila.
15. Spoj prema zahtjevu 14, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što svaki od R4A, R5A, R6A, R7A i R8A je H.
16. Spoj prema zahtjevu 1, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što R9 je neovisno odabran od H, -C1-6alkila, -C2-6alkenila, ili -C1-6alkil-O-C1-6alkila ili -C1-6haloalkila.
17. Spoj prema zahtjevu 16, ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, naznačen time što R9 je H, -CH3, ili -CH2CH3.
18. Spoj prema zahtjevu 1, naznačen time što spoj s Formulom I' ima Formulu II':
[image]
ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, pri čemu su R4, R5, R9 i R9A kako je definirano iznad.
19. Spoj prema zahtjevu 1, naznačen time što spoj s Formulom I' ima Formulu II'a:
[image]
ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, pri čemu su R4, R5, R9 i R9A kako je definirano iznad.
20. Spoj prema zahtjevu 1, naznačen time što spoj s Formulom I' ima Formulu IV':
[image]
ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera pri čemu su R4, R5, R9 i R9A kako je definirano iznad.
21. Spoj prema zahtjevu 1, naznačen time što spoj s Formulom I' ima Formulu IV'a:
[image]
ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera, pri čemu su R4, R5, R9 i R9A kako je definirano iznad.
22. Spoj prema zahtjevu 1, naznačen time što spoj ima strukturu odabranu od:
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ili
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ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera.
23. Spoj prema zahtjevu 22 ili njegova farmaceutski prihvatljiva sol.
24. Spoj prema zahtjevu 1, naznačen time što je spoj odabran od:
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ili
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ili njegov stereoizomer, njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiva sol njegovog stereoizomera.
25. Spoj prema zahtjevu 24 ili njegova farmaceutski prihvatljiva sol.
26. Spoj prema zahtjevu 24, naznačen time što je spoj
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ili je njegova farmaceutski prihvatljiva sol.
27. Spoj prema zahtjevu 24, naznačen time što je spoj
[image]
ili je njegova farmaceutski prihvatljiva sol.
28. Spoj prema zahtjevu 24, naznačen time što je spoj
[image]
ili je njegova farmaceutski prihvatljiva sol.
29. Spoj prema zahtjevu 24, naznačen time što je spoj
[image]
ili je njegova farmaceutski prihvatljiva sol.
30. Spoj prema zahtjevu 1, naznačen time što je spoj
[image]
ili je njegova farmaceutski prihvatljiva sol.
31. Farmaceutski pripravak naznačen time što sadrži spoj prema bilo kojem od zahtjeva 1-30 ili njegovu farmaceutski prihvatljivu sol, i farmaceutski prihvatljiv nosač ili razrjeđivač.
32. Farmaceutski pripravak naznačen time što sadrži spoj prema zahtjevu 26 ili njegovu farmaceutski prihvatljivu sol, i farmaceutski prihvatljiv nosač ili razrjeđivač.
33. Farmaceutski pripravak naznačen time što sadrži spoj prema zahtjevu 27 ili njegovu farmaceutski prihvatljivu sol, i farmaceutski prihvatljiv nosač ili razrjeđivač.
34. Farmaceutski pripravak naznačen time što sadrži spoj prema zahtjevu 28 ili njegovu farmaceutski prihvatljivu sol, i farmaceutski prihvatljiv nosač ili razrjeđivač.
35. Farmaceutski pripravak naznačen time što sadrži spoj prema zahtjevu 29 ili njegovu farmaceutski prihvatljivu sol, i farmaceutski prihvatljiv nosač ili razrjeđivač.
36. Spoj prema bilo kojem od zahtjeva 1-30 za upotrebu u liječenju raka.
37. Spoj za upotrebu prema zahtjevu 36, naznačen time što je rak hematološki zloćudni tumor.
38. Spoj za upotrebu prema zahtjevu 36, naznačen time što je rak odabran iz skupine koju čine rak dojke, kolorektalni karcinom, rak kože, melanom, rak jajnika, rak bubrega, rak pluća, rak pluća ne-malih stanica, limfom, ne-Hodgkinov limfom, mijelom, multipli mijelom, leukemija i akutna mijeloična leukemija.
39. Spoj za upotrebu prema zahtjevu 36, naznačen time što je rak multipli mijelom, akutna mijeloična leukemija ili ne-Hodgkinov limfom.
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| EP18717811.6A EP3601297B9 (en) | 2017-03-30 | 2018-03-28 | Compounds that inhibit mcl-1 protein |
| PCT/US2018/024723 WO2018183418A1 (en) | 2017-03-30 | 2018-03-28 | Compounds that inhibit mcl-1 protein |
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| HRP20221412T2 HRP20221412T2 (hr) | 2023-11-24 |
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| HRP20221412TT HRP20221412T2 (hr) | 2017-03-30 | 2018-03-28 | Spojevi koji inhibiraju mcl-1 protein |
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| US11364248B2 (en) | 2017-08-18 | 2022-06-21 | Amgen Inc. | Compounds that inhibit Mcl-1 protein |
| US11279712B2 (en) | 2017-08-29 | 2022-03-22 | Amgen Inc. | Macrocyclic compounds that inhibit MCL-1 protein |
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2018
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