HRP20221412T2 - Spojevi koji inhibiraju mcl-1 protein - Google Patents
Spojevi koji inhibiraju mcl-1 protein Download PDFInfo
- Publication number
- HRP20221412T2 HRP20221412T2 HRP20221412TT HRP20221412T HRP20221412T2 HR P20221412 T2 HRP20221412 T2 HR P20221412T2 HR P20221412T T HRP20221412T T HR P20221412TT HR P20221412 T HRP20221412 T HR P20221412T HR P20221412 T2 HRP20221412 T2 HR P20221412T2
- Authority
- HR
- Croatia
- Prior art keywords
- image
- pharmaceutically acceptable
- acceptable salt
- 6alkyl
- stereoisomer
- Prior art date
Links
- 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
- 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
- 125000000217 alkyl group Chemical group 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (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':
[image]
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,
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
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:
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
ili
[image]
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:
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
ili
[image]
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
[image]
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.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762479171P | 2017-03-30 | 2017-03-30 | |
| US201762479230P | 2017-03-30 | 2017-03-30 | |
| 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 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HRP20221412T1 HRP20221412T1 (hr) | 2023-01-06 |
| HRP20221412T2 true HRP20221412T2 (hr) | 2023-11-24 |
Family
ID=61972255
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20221412TT HRP20221412T2 (hr) | 2017-03-30 | 2018-03-28 | Spojevi koji inhibiraju mcl-1 protein |
Country Status (33)
| Country | Link |
|---|---|
| US (5) | US10300075B2 (hr) |
| EP (1) | EP3601297B9 (hr) |
| JP (2) | JP6453507B2 (hr) |
| KR (1) | KR102372322B1 (hr) |
| CN (1) | CN110691784B (hr) |
| AU (2) | AU2018244349B2 (hr) |
| BR (1) | BR112019020459B1 (hr) |
| CA (1) | CA3057882A1 (hr) |
| CL (1) | CL2019002777A1 (hr) |
| CO (1) | CO2019011762A2 (hr) |
| CR (1) | CR20190489A (hr) |
| DK (1) | DK3601297T5 (hr) |
| ES (1) | ES2940641T3 (hr) |
| FI (1) | FI3601297T3 (hr) |
| HR (1) | HRP20221412T2 (hr) |
| HU (1) | HUE060919T2 (hr) |
| IL (1) | IL269603B (hr) |
| JO (1) | JOP20190229B1 (hr) |
| LT (1) | LT3601297T (hr) |
| MX (1) | MX2019011693A (hr) |
| NZ (1) | NZ757606A (hr) |
| PE (1) | PE20200335A1 (hr) |
| PH (1) | PH12019502245A1 (hr) |
| PL (1) | PL3601297T3 (hr) |
| PT (1) | PT3601297T (hr) |
| RS (1) | RS63892B9 (hr) |
| SA (1) | SA519410222B1 (hr) |
| SG (1) | SG11201908945RA (hr) |
| SI (1) | SI3601297T1 (hr) |
| TW (1) | TWI685493B (hr) |
| UA (1) | UA124784C2 (hr) |
| UY (1) | UY37656A (hr) |
| WO (1) | WO2018183418A1 (hr) |
Families Citing this family (70)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT3570844T (pt) | 2017-01-20 | 2023-11-15 | Arcus Biosciences Inc | Azolopirimidina para o tratamento de doenças relacionadas com o cancro |
| JP6453507B2 (ja) | 2017-03-30 | 2019-01-16 | アムジエン・インコーポレーテツド | Ｍｃｌ−１タンパク質を阻害する化合物 |
| CR20190424A (es) | 2017-03-30 | 2019-11-04 | Hoffmann La Roche | Isoquinolinas como inhibidores de hpk1 |
| JOP20180029A1 (ar) | 2017-03-30 | 2019-01-30 | Takeda Pharmaceuticals Co | مركب حلقي غير متجانس |
| MA49908A (fr) | 2017-08-18 | 2021-04-28 | Amgen Inc | Composés inhibant la protéine mcl-1 |
| MA50033A (fr) | 2017-08-29 | 2020-07-08 | Amgen Inc | Composés macrocycliques permettant d'inhiber la protéine mcl-1 |
| US11271966B2 (en) * | 2018-02-09 | 2022-03-08 | Bolster, Inc | Real-time detection and redirecton from counterfeit websites |
| US11301560B2 (en) * | 2018-02-09 | 2022-04-12 | Bolster, Inc | Real-time detection and blocking of counterfeit websites |
| US12041084B2 (en) | 2018-02-09 | 2024-07-16 | Bolster, Inc | Systems and methods for determining user intent at a website and responding to the user intent |
| CA3090922A1 (en) | 2018-02-16 | 2019-08-22 | Arcus Biosciences, Inc. | Dosing with an azolopyrimidine compound |
| EP3762393B1 (en) | 2018-03-05 | 2023-01-11 | Amgen Inc. | Alpha-hydroxy phenylacetic acid pharmacophore or bioisostere mcl-1 protein antagonists |
| PL3793565T3 (pl) | 2018-05-14 | 2022-05-02 | Gilead Sciences, Inc. | Inhibitory MCL-1 |
| US11612606B2 (en) | 2018-10-03 | 2023-03-28 | Genentech, Inc. | 8-aminoisoquinoline compounds and uses thereof |
| KR20210089662A (ko) * | 2018-11-09 | 2021-07-16 | 프렐루드 테라퓨틱스, 인코포레이티드 | 골수 세포 백혈병-1 (mcl-1) 단백질의 억제제로서 스피로-술폰아미드 유도체 |
| TWI745836B (zh) * | 2019-01-18 | 2021-11-11 | 大陸商蘇州亞盛藥業有限公司 | 作為mcl-1抑製劑的大螺環醚 |
| WO2020151738A1 (en) * | 2019-01-23 | 2020-07-30 | Ascentage Pharma (Suzhou) Co., Ltd. | Macrocyclic fused pyrrazoles as mcl-1 inhibitors |
| KR20220017931A (ko) | 2019-05-20 | 2022-02-14 | 노파르티스 아게 | Mcl-1 억제제 항체-약물 접합체 및 사용 방법 |
| WO2020237025A1 (en) | 2019-05-23 | 2020-11-26 | Gilead Sciences, Inc. | Substituted exo-methylene-oxindoles which are hpk1/map4k1 inhibitors |
| CA3142513A1 (en) | 2019-06-25 | 2020-12-30 | Gilead Sciences, Inc. | Flt3l-fc fusion proteins and methods of use |
| AU2020309745A1 (en) | 2019-07-09 | 2022-03-03 | Janssen Pharmaceutica Nv | Macrocyclic spirocycle derivatives as MCL-1 inhibitors |
| EP4045083B1 (en) | 2019-10-18 | 2024-01-10 | Forty Seven, Inc. | Combination therapies for treating myelodysplastic syndromes and acute myeloid leukemia |
| CN114599392A (zh) | 2019-10-31 | 2022-06-07 | 四十七公司 | 基于抗cd47和抗cd20的血癌治疗 |
| TWI778443B (zh) | 2019-11-12 | 2022-09-21 | 美商基利科學股份有限公司 | Mcl1抑制劑 |
| JP7441947B2 (ja) | 2019-11-26 | 2024-03-01 | ギリアード サイエンシーズ， インコーポレイテッド | Ｍｃｌ１阻害剤を調製するためのプロセス及び中間体 |
| CN117736207A (zh) | 2019-12-24 | 2024-03-22 | 卡尔那生物科学株式会社 | 二酰基甘油激酶调节化合物 |
| CN117964757A (zh) | 2020-02-14 | 2024-05-03 | 吉利德科学公司 | 与ccr8结合的抗体和融合蛋白及其用途 |
| JP2021161114A (ja) * | 2020-03-31 | 2021-10-11 | アムジエン・インコーポレーテツド | Ｍｃｌ−１化合物のメチル化 |
| WO2021211922A1 (en) * | 2020-04-16 | 2021-10-21 | Prelude Therapeutics, Incorporated | Spiro-sulfonimidamide derivatives as inhibitors of myeloid cell leukemia-1 (mcl-1) protein |
| US12110294B2 (en) | 2020-05-01 | 2024-10-08 | Gilead Sciences, Inc. | CD73 compounds |
| WO2021225833A1 (en) | 2020-05-06 | 2021-11-11 | Amgen Inc. | Synthesis of sulfonamide intermediates |
| TW202208342A (zh) | 2020-05-06 | 2022-03-01 | 美商安進公司 | 乙烯基環丁基中間體之合成 |
| TWI827924B (zh) | 2020-05-06 | 2024-01-01 | 美商安進公司 | 大環Mcl-1抑制劑中間體的閉環合成 |
| CN115485268B (zh) * | 2020-05-06 | 2024-06-18 | 安进公司 | 乙烯基保护的醇中间体的合成 |
| US20230136910A1 (en) * | 2020-05-06 | 2023-05-04 | Amgen Inc. | Synthesis of vinylic alcohol intermediates |
| KR20230024287A (ko) * | 2020-05-13 | 2023-02-20 | 프렐루드 테라퓨틱스, 인코포레이티드 | 골수 세포 백혈병-1 (mcl-1) 단백질의 억제제로서의 스피로-술폰아미드 유도체 |
| JP2023528965A (ja) * | 2020-06-10 | 2023-07-06 | ヤンセン ファーマシューティカ エヌ．ベー． | Ｍｃｌ－１の阻害剤としての大環状２－アミノ－３－フルオロ－ブタ－３－エナミド |
| JP2022039996A (ja) * | 2020-08-26 | 2022-03-10 | アムジエン・インコーポレーテツド | Ｍｃｌ－１阻害剤処方物 |
| WO2022051317A1 (en) | 2020-09-03 | 2022-03-10 | Amgen Inc. | Diol desymmetrization by nucleophilic aromatic substitution |
| JP2023550612A (ja) * | 2020-11-19 | 2023-12-04 | ギリアード サイエンシーズ， インコーポレイテッド | 大環状ｍｃｌ１阻害剤を調製するための方法及び中間体 |
| WO2022115451A1 (en) | 2020-11-24 | 2022-06-02 | Novartis Ag | Mcl-1 inhibitor antibody-drug conjugates and methods of use |
| MX2023006144A (es) * | 2020-11-25 | 2023-06-06 | Amgen Inc | Alquenilacion enantioselectiva de aldehidos. |
| AU2021404501A1 (en) | 2020-12-17 | 2023-08-03 | Janssen Pharmaceutica Nv | Macrocyclic branched 3-fluoro-but-3-enamides as inhibitors of mcl-1 |
| TW202302145A (zh) | 2021-04-14 | 2023-01-16 | 美商基利科學股份有限公司 | ＣＤ４７／ＳＩＲＰα結合及ＮＥＤＤ８活化酶Ｅ１調節次單元之共抑制以用於治療癌症 |
| CA3215312A1 (en) | 2021-04-26 | 2022-11-03 | Frederik Jan Rita Rombouts | Macrocyclic 2-allyltetrahydrofurans as inhibitors of mcl-1 |
| TW202313094A (zh) | 2021-05-18 | 2023-04-01 | 美商基利科學股份有限公司 | 使用ＦＬＴ３Ｌ—Ｆｃ融合蛋白之方法 |
| TW202317200A (zh) | 2021-06-11 | 2023-05-01 | 美商基利科學股份有限公司 | Ｍｃｌ－１抑制劑與抗體藥物接合物之組合 |
| TW202315637A (zh) | 2021-06-11 | 2023-04-16 | 美商基利科學股份有限公司 | Mcl-1抑制劑與抗癌劑之組合 |
| US11932634B2 (en) | 2021-06-23 | 2024-03-19 | Gilead Sciences, Inc. | Diacylglycerol kinase modulating compounds |
| EP4359415A1 (en) | 2021-06-23 | 2024-05-01 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| EP4359411A1 (en) | 2021-06-23 | 2024-05-01 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| CN117396478A (zh) | 2021-06-23 | 2024-01-12 | 吉利德科学公司 | 二酰基甘油激酶调节化合物 |
| WO2023057484A1 (en) | 2021-10-06 | 2023-04-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting and improving the efficacy of mcl-1 inhibitor therapy |
| WO2023076983A1 (en) | 2021-10-28 | 2023-05-04 | Gilead Sciences, Inc. | Pyridizin-3(2h)-one derivatives |
| MX2024005066A (es) | 2021-10-29 | 2024-05-24 | Gilead Sciences Inc | Compuestos de cd73. |
| CA3237011A1 (en) | 2021-11-16 | 2023-05-25 | Soufyan JERHAOUI | Macrocyclic 2-amino-but-3-enamides as inhibitors of mcl-1 |
| US20230220106A1 (en) | 2021-12-08 | 2023-07-13 | Dragonfly Therapeutics, Inc. | Antibodies targeting 5t4 and uses thereof |
| WO2023107956A1 (en) | 2021-12-08 | 2023-06-15 | Dragonfly Therapeutics, Inc. | Proteins binding nkg2d, cd16 and 5t4 |
| WO2023122581A2 (en) | 2021-12-22 | 2023-06-29 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
| WO2023122615A1 (en) | 2021-12-22 | 2023-06-29 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
| TW202340168A (zh) | 2022-01-28 | 2023-10-16 | 美商基利科學股份有限公司 | Ｐａｒｐ７抑制劑 |
| MX2024009448A (es) | 2022-02-04 | 2024-08-15 | Amgen Inc | Formas cristalinas de un inhibidor de mcl-1. |
| AU2023215171A1 (en) * | 2022-02-04 | 2024-07-04 | Amgen Inc. | Crystalline salt and solvate forms of murizatoclax (amg 397) |
| IL315083A (en) | 2022-03-17 | 2024-10-01 | Gilead Sciences Inc | The IKAROS family of zinc fingers degrades and uses them |
| US20230355796A1 (en) | 2022-03-24 | 2023-11-09 | Gilead Sciences, Inc. | Combination therapy for treating trop-2 expressing cancers |
| TW202345901A (zh) | 2022-04-05 | 2023-12-01 | 美商基利科學股份有限公司 | 用於治療結腸直腸癌之組合療法 |
| AU2023256670A1 (en) | 2022-04-21 | 2024-10-17 | Gilead Sciences, Inc. | Kras g12d modulating compounds |
| TW202408588A (zh) | 2022-05-20 | 2024-03-01 | 瑞士商諾華公司 | 抗體-藥物結合物抗腫瘤化合物及其使用方法 |
| US20240116928A1 (en) | 2022-07-01 | 2024-04-11 | Gilead Sciences, Inc. | Cd73 compounds |
| US20240091351A1 (en) | 2022-09-21 | 2024-03-21 | Gilead Sciences, Inc. | FOCAL IONIZING RADIATION AND CD47/SIRPa DISRUPTION ANTICANCER COMBINATION THERAPY |
| US20240254118A1 (en) | 2022-12-22 | 2024-08-01 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US5858784A (en) | 1991-12-17 | 1999-01-12 | The Regents Of The University Of California | Expression of cloned genes in the lung by aerosol- and liposome-based delivery |
| US6042820A (en) | 1996-12-20 | 2000-03-28 | Connaught Laboratories Limited | Biodegradable copolymer containing α-hydroxy acid and α-amino acid units |
| US6472375B1 (en) | 1998-04-16 | 2002-10-29 | John Wayne Cancer Institute | DNA vaccine and methods for its use |
| AU2008242983B2 (en) | 2007-04-16 | 2013-07-11 | Abbvie Inc. | 7-substituted indole Mcl-1 inhibitors |
| AU2011210567B2 (en) | 2010-01-29 | 2015-04-16 | Dana-Farber Cancer Institute, Inc. | Small molecules for the modulation of MCL-1 and methods of modulatiing cell death, cell division, cell differentiation and methods of treating disorders |
| RU2635156C2 (ru) | 2011-08-31 | 2017-11-09 | Авери Деннисон Корпорейшн | Адгезионные сополимеры акрилатов и олефинов, способы их получения и использующие их композиции |
| WO2013052943A2 (en) | 2011-10-06 | 2013-04-11 | The Regents Of The University Of Michgian | Small molecule inhibitors of mcl-1 and uses thereof |
| US9914723B2 (en) | 2012-03-29 | 2018-03-13 | The Regents Of The University Of Michigan | Small molecule inhibitors of Mcl-1 and uses thereof |
| US10533010B2 (en) * | 2014-03-27 | 2020-01-14 | Vanderbilt University | Substituted indole Mcl-1 inhibitors |
| JO3474B1 (ar) | 2014-08-29 | 2020-07-05 | Amgen Inc | مشتقات تيتراهيدرونافثالين التي تثبط بروتين mcl-1 |
| US11306107B2 (en) * | 2016-02-25 | 2022-04-19 | Amgen Inc. | Compounds that inhibit MCL-1 protein |
| JP6786892B2 (ja) | 2016-06-09 | 2020-11-18 | 富士ゼロックス株式会社 | サーバ装置、情報処理システム及びプログラム |
| JP6453507B2 (ja) | 2017-03-30 | 2019-01-16 | アムジエン・インコーポレーテツド | Ｍｃｌ−１タンパク質を阻害する化合物 |
| MA49908A (fr) | 2017-08-18 | 2021-04-28 | Amgen Inc | Composés inhibant la protéine mcl-1 |
| MA50033A (fr) | 2017-08-29 | 2020-07-08 | Amgen Inc | Composés macrocycliques permettant d'inhiber la protéine mcl-1 |
-
2018
- 2018-03-27 JP JP2018059341A patent/JP6453507B2/ja active Active
- 2018-03-28 PL PL18717811.6T patent/PL3601297T3/pl unknown
- 2018-03-28 LT LTEPPCT/US2018/024723T patent/LT3601297T/lt unknown
- 2018-03-28 ES ES18717811T patent/ES2940641T3/es active Active
- 2018-03-28 HR HRP20221412TT patent/HRP20221412T2/hr unknown
- 2018-03-28 SI SI201830809T patent/SI3601297T1/sl unknown
- 2018-03-28 RS RS20230036A patent/RS63892B9/sr unknown
- 2018-03-28 PE PE2019001963A patent/PE20200335A1/es unknown
- 2018-03-28 NZ NZ757606A patent/NZ757606A/en unknown
- 2018-03-28 WO PCT/US2018/024723 patent/WO2018183418A1/en unknown
- 2018-03-28 AU AU2018244349A patent/AU2018244349B2/en active Active
- 2018-03-28 BR BR112019020459-8A patent/BR112019020459B1/pt active IP Right Grant
- 2018-03-28 SG SG11201908945R patent/SG11201908945RA/en unknown
- 2018-03-28 FI FIEP18717811.6T patent/FI3601297T3/fi active
- 2018-03-28 KR KR1020197029091A patent/KR102372322B1/ko active IP Right Grant
- 2018-03-28 PT PT187178116T patent/PT3601297T/pt unknown
- 2018-03-28 US US15/938,001 patent/US10300075B2/en active Active
- 2018-03-28 EP EP18717811.6A patent/EP3601297B9/en active Active
- 2018-03-28 HU HUE18717811A patent/HUE060919T2/hu unknown
- 2018-03-28 MX MX2019011693A patent/MX2019011693A/es unknown
- 2018-03-28 CN CN201880035818.3A patent/CN110691784B/zh active Active
- 2018-03-28 UA UAA201910703A patent/UA124784C2/uk unknown
- 2018-03-28 JO JOP/2019/0229A patent/JOP20190229B1/ar active
- 2018-03-28 DK DK18717811.6T patent/DK3601297T5/da active
- 2018-03-28 CA CA3057882A patent/CA3057882A1/en active Pending
- 2018-03-28 CR CR20190489A patent/CR20190489A/es unknown
- 2018-03-30 TW TW107111110A patent/TWI685493B/zh active
- 2018-04-02 UY UY0001037656A patent/UY37656A/es unknown
- 2018-12-11 JP JP2018231352A patent/JP6629419B2/ja active Active
-
2019
- 2019-03-11 US US16/297,904 patent/US10500213B2/en active Active
- 2019-08-22 US US16/547,747 patent/US10632128B2/en active Active
- 2019-09-24 IL IL269603A patent/IL269603B/en unknown
- 2019-09-27 CL CL2019002777A patent/CL2019002777A1/es unknown
- 2019-09-27 PH PH12019502245A patent/PH12019502245A1/en unknown
- 2019-09-30 SA SA519410222A patent/SA519410222B1/ar unknown
- 2019-10-24 CO CONC2019/0011762A patent/CO2019011762A2/es unknown
-
2020
- 2020-02-06 US US16/783,269 patent/US10821115B2/en active Active
- 2020-09-23 US US17/029,249 patent/US11224601B1/en active Active
-
2021
- 2021-01-15 AU AU2021200233A patent/AU2021200233A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20221412T2 (hr) | Spojevi koji inhibiraju mcl-1 protein | |
| CY1122542T1 (el) | Νεα παραγωγα υδροξυεστερα, μια διεργασια για την παρασκευη αυτων και φαρμακευτικες συνθεσεις που περιεχουν αυτα | |
| RU2015141592A (ru) | АРИЛ-СУЛЬФАМИДЫ И СУЛЬФАМАТЫ В КАЧЕСТВЕ МОДУЛЯТОРОВ RORc | |
| RU2019133646A (ru) | Изохинолины в качестве ингибиторов hpk1 | |
| HRP20171107T1 (hr) | Pripravci i postupci za modulatore apoptoze | |
| IL274568B (en) | Modulators of cot and methods of using them | |
| DK155187C (da) | Analogifremgangsmaade til fremstilling af cephalosporinforbindelser i den syn-isomere form eller ugiftige salte deraf | |
| HRP20220628T1 (hr) | Postupci i međuprodukti za pripremu lijeka | |
| JP2017501237A5 (hr) | ||
| NL164832B (nl) | Werkwijze voor het bereiden van een stabiele oplossing van een basisch aluminiumzout. | |
| JP2016515560A5 (hr) | ||
| JP2016504365A5 (hr) | ||
| DK157320C (da) | Analogifremgangsmaade til fremstilling af 3-carbamoyloxy-methyl-7alfa-methoxy-7beta-(2-thienylacetamido)-3-cephem-4-carboxylsyre eller salte deraf | |
| WO2015021396A3 (en) | Tricyclic benzoxaborole compounds and uses thereof | |
| RU2015125591A (ru) | БЕНЗИЛСУЛЬФОНАМИДНЫЕ ПРОИЗВОДНЫЕ КАК МОДУЛЯТОРЫ RORc | |
| DK147683C (da) | Analogifremgangsmaade til fremstilling af cephalosporinforbindelser eller ugiftige salte, biologisk acceptable estere, 1-oxyder eller solvater deraf | |
| RU2020108580A (ru) | Лекарственное соединение и способы его очистки | |
| DK348678A (da) | 3-hydroxycrotonsyrederivater til anvendelse som mellemprodukter ved fremstillingen af antiobiotisk virksomme 3-cephemforbindelser | |
| IL274229B2 (en) | Antibacterial compounds | |
| MX2020008110A (es) | Sal de compuesto de pirazolo[1,5-a]pirimidina y cristales de la misma. | |
| DK319886A (da) | Kemiske forbindelser | |
| IT1015007B (it) | Centrifuga per vetrini macchia ti di sangue | |
| NL7412827A (nl) | Werkwijze voor het bereiden van gesubstitueer- danoloxyazijnzuurverbindingen; werkwijze ereiding van farmaceutische preparaten, de de door toepassing daarvan verkregen erpen. | |
| NL7600846A (nl) | Werkwijze voor het bereiden van nieuwe naftaleen- verbindingen, alsmede deze verbindingen bevattende farmaceutische preparaten. | |
| IT1026675B (it) | Apparecchio per rendere asettico il campo di operazioni chirurgi che |