BR112019005337A2 - terapia combinada - Google Patents
terapia combinada Download PDFInfo
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- BR112019005337A2 BR112019005337A2 BR112019005337A BR112019005337A BR112019005337A2 BR 112019005337 A2 BR112019005337 A2 BR 112019005337A2 BR 112019005337 A BR112019005337 A BR 112019005337A BR 112019005337 A BR112019005337 A BR 112019005337A BR 112019005337 A2 BR112019005337 A2 BR 112019005337A2
- Authority
- BR
- Brazil
- Prior art keywords
- certain embodiments
- compound
- substituents
- hydrogen
- alkyl
- Prior art date
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- 238000002648 combination therapy Methods 0.000 title abstract description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 64
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 63
- 238000000034 method Methods 0.000 claims abstract description 58
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 49
- 201000010099 disease Diseases 0.000 claims abstract description 47
- 229940124291 BTK inhibitor Drugs 0.000 claims abstract description 44
- 239000003112 inhibitor Substances 0.000 claims abstract description 43
- 201000011510 cancer Diseases 0.000 claims abstract description 39
- 239000012664 BCL-2-inhibitor Substances 0.000 claims abstract description 30
- 229940123711 Bcl2 inhibitor Drugs 0.000 claims abstract description 30
- 125000001424 substituent group Chemical group 0.000 claims description 444
- 150000001875 compounds Chemical class 0.000 claims description 427
- -1 heteroalkenylene Chemical group 0.000 claims description 368
- 229910052739 hydrogen Inorganic materials 0.000 claims description 304
- 239000001257 hydrogen Substances 0.000 claims description 304
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 244
- 125000000623 heterocyclic group Chemical group 0.000 claims description 206
- 150000003839 salts Chemical class 0.000 claims description 187
- 125000003118 aryl group Chemical group 0.000 claims description 181
- 230000000155 isotopic effect Effects 0.000 claims description 177
- 125000001072 heteroaryl group Chemical group 0.000 claims description 174
- 239000012453 solvate Substances 0.000 claims description 172
- 229940002612 prodrug Drugs 0.000 claims description 169
- 239000000651 prodrug Substances 0.000 claims description 169
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 130
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 96
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 90
- 125000000217 alkyl group Chemical group 0.000 claims description 84
- 125000004432 carbon atom Chemical group C* 0.000 claims description 83
- 125000005843 halogen group Chemical group 0.000 claims description 83
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 64
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 58
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 56
- 229910052799 carbon Inorganic materials 0.000 claims description 53
- 125000003342 alkenyl group Chemical group 0.000 claims description 41
- 125000000304 alkynyl group Chemical group 0.000 claims description 34
- 150000002431 hydrogen Chemical class 0.000 claims description 32
- 102100038970 Histone-lysine N-methyltransferase EZH2 Human genes 0.000 claims description 31
- 101000882127 Homo sapiens Histone-lysine N-methyltransferase EZH2 Proteins 0.000 claims description 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 27
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 26
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
- 125000004474 heteroalkylene group Chemical group 0.000 claims description 22
- 239000002177 L01XE27 - Ibrutinib Substances 0.000 claims description 19
- 125000002947 alkylene group Chemical group 0.000 claims description 19
- XYFPWWZEPKGCCK-GOSISDBHSA-N ibrutinib Chemical group C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-GOSISDBHSA-N 0.000 claims description 19
- 229960001507 ibrutinib Drugs 0.000 claims description 19
- NSQSAUGJQHDYNO-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-[ethyl(oxan-4-yl)amino]-2-methyl-5-[4-(morpholin-4-ylmethyl)phenyl]benzamide Chemical group C=1C(C=2C=CC(CN3CCOCC3)=CC=2)=CC(C(=O)NCC=2C(NC(C)=CC=2C)=O)=C(C)C=1N(CC)C1CCOCC1 NSQSAUGJQHDYNO-UHFFFAOYSA-N 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 17
- LQBVNQSMGBZMKD-UHFFFAOYSA-N venetoclax Chemical group C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCOCC1 LQBVNQSMGBZMKD-UHFFFAOYSA-N 0.000 claims description 17
- 125000004450 alkenylene group Chemical group 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 229960001183 venetoclax Drugs 0.000 claims description 16
- RNOAOAWBMHREKO-QFIPXVFZSA-N (7S)-2-(4-phenoxyphenyl)-7-(1-prop-2-enoylpiperidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C(C=C)(=O)N1CCC(CC1)[C@@H]1CCNC=2N1N=C(C=2C(=O)N)C1=CC=C(C=C1)OC1=CC=CC=C1 RNOAOAWBMHREKO-QFIPXVFZSA-N 0.000 claims description 14
- 125000006717 (C3-C10) cycloalkenyl group Chemical group 0.000 claims description 14
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 14
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 14
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 12
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 12
- 208000023275 Autoimmune disease Diseases 0.000 claims description 12
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 229950004774 tazemetostat Drugs 0.000 claims description 12
- 208000003950 B-cell lymphoma Diseases 0.000 claims description 11
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims description 11
- 102100029823 Tyrosine-protein kinase BTK Human genes 0.000 claims description 11
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 11
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 10
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 10
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 9
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 8
- VVLHQJDAUIPZFH-UHFFFAOYSA-N 4-[4-[[5-fluoro-4-[3-(prop-2-enoylamino)anilino]pyrimidin-2-yl]amino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC=3N=C(NC=4C=C(NC(=O)C=C)C=CC=4)C(F)=CN=3)=CC=2)=C1 VVLHQJDAUIPZFH-UHFFFAOYSA-N 0.000 claims description 8
- DNVXATUJJDPFDM-KRWDZBQOSA-N JQ1 Chemical compound N([C@@H](CC(=O)OC(C)(C)C)C1=NN=C(N1C=1SC(C)=C(C)C=11)C)=C1C1=CC=C(Cl)C=C1 DNVXATUJJDPFDM-KRWDZBQOSA-N 0.000 claims description 8
- 125000004043 oxo group Chemical group O=* 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 230000002265 prevention Effects 0.000 claims description 6
- AAAQFGUYHFJNHI-SFHVURJKSA-N 2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide Chemical compound N([C@H](C1=NN=C(C)N1C1=CC=C(OC)C=C11)CC(=O)NCC)=C1C1=CC=C(Cl)C=C1 AAAQFGUYHFJNHI-SFHVURJKSA-N 0.000 claims description 4
- TXZPMHLMPKIUGK-UHFFFAOYSA-N 2-methoxy-N-(3-methyl-2-oxo-1,4-dihydroquinazolin-6-yl)benzenesulfonamide Chemical compound COC1=CC=CC=C1S(=O)(=O)NC1=CC=C(NC(=O)N(C)C2)C2=C1 TXZPMHLMPKIUGK-UHFFFAOYSA-N 0.000 claims description 4
- JIFCFQDXHMUPGP-UHFFFAOYSA-N 4-tert-butyl-n-[2-methyl-3-[4-methyl-6-[4-(morpholine-4-carbonyl)anilino]-5-oxopyrazin-2-yl]phenyl]benzamide Chemical compound C1=CC=C(C=2N=C(NC=3C=CC(=CC=3)C(=O)N3CCOCC3)C(=O)N(C)C=2)C(C)=C1NC(=O)C1=CC=C(C(C)(C)C)C=C1 JIFCFQDXHMUPGP-UHFFFAOYSA-N 0.000 claims description 4
- ZTUJNJAKTLHBEX-UHFFFAOYSA-N 6-cyclopropyl-8-fluoro-2-[2-(hydroxymethyl)-3-[1-methyl-5-[[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino]-6-oxopyridin-3-yl]phenyl]isoquinolin-1-one Chemical compound C1CN(C)CCN1C(C=N1)=CC=C1NC1=CC(C=2C(=C(C=CC=2)N2C(C3=C(F)C=C(C=C3C=C2)C2CC2)=O)CO)=CN(C)C1=O ZTUJNJAKTLHBEX-UHFFFAOYSA-N 0.000 claims description 4
- GNMUEVRJHCWKTO-FQEVSTJZSA-N 6h-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide, 4-(4-chlorophenyl)-n-(4-hydroxyphenyl)-2,3,9-trimethyl-, (6s)- Chemical compound C([C@@H]1N=C(C2=C(N3C(C)=NN=C31)SC(=C2C)C)C=1C=CC(Cl)=CC=1)C(=O)NC1=CC=C(O)C=C1 GNMUEVRJHCWKTO-FQEVSTJZSA-N 0.000 claims description 4
- VUVUVNZRUGEAHB-CYBMUJFWSA-N 7-(3,5-dimethyl-4-isoxazolyl)-8-methoxy-1-[(1R)-1-(2-pyridinyl)ethyl]-3H-imidazo[4,5-c]quinolin-2-one Chemical compound C1([C@@H](C)N2C3=C4C=C(C(=CC4=NC=C3NC2=O)C2=C(ON=C2C)C)OC)=CC=CC=N1 VUVUVNZRUGEAHB-CYBMUJFWSA-N 0.000 claims description 4
- NETXMUIMUZJUTB-UHFFFAOYSA-N apabetalone Chemical compound C=1C(OC)=CC(OC)=C(C(N2)=O)C=1N=C2C1=CC(C)=C(OCCO)C(C)=C1 NETXMUIMUZJUTB-UHFFFAOYSA-N 0.000 claims description 4
- 229950000080 birabresib Drugs 0.000 claims description 4
- SEJLPXCPMNSRAM-GOSISDBHSA-N 6-amino-9-[(3r)-1-but-2-ynoylpyrrolidin-3-yl]-7-(4-phenoxyphenyl)purin-8-one Chemical compound C1N(C(=O)C#CC)CC[C@H]1N1C(=O)N(C=2C=CC(OC=3C=CC=CC=3)=CC=2)C2=C(N)N=CN=C21 SEJLPXCPMNSRAM-GOSISDBHSA-N 0.000 claims description 3
- MQIGTEQXYCRLGK-BQBZGAKWSA-N Ala-Gly-Pro Chemical compound C[C@H](N)C(=O)NCC(=O)N1CCC[C@H]1C(O)=O MQIGTEQXYCRLGK-BQBZGAKWSA-N 0.000 claims description 3
- UVSVTDVJQAJIFG-VURMDHGXSA-N LFM-A13 Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC(Br)=CC=C1Br UVSVTDVJQAJIFG-VURMDHGXSA-N 0.000 claims description 3
- 210000001102 germinal center b cell Anatomy 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 claims 2
- ABSXPNGWJFAPRT-UHFFFAOYSA-N benzenesulfonic acid;n-[3-[[5-fluoro-2-[4-(2-methoxyethoxy)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide Chemical compound OS(=O)(=O)C1=CC=CC=C1.C1=CC(OCCOC)=CC=C1NC1=NC=C(F)C(NC=2C=C(NC(=O)C=C)C=CC=2)=N1 ABSXPNGWJFAPRT-UHFFFAOYSA-N 0.000 claims 1
- GCWIQUVXWZWCLE-INIZCTEOSA-N pelabresib Chemical compound N([C@@H](CC(N)=O)C=1ON=C(C=1C1=CC=CC=C11)C)=C1C1=CC=C(Cl)C=C1 GCWIQUVXWZWCLE-INIZCTEOSA-N 0.000 claims 1
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 abstract description 54
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 abstract description 22
- 229940125814 BTK kinase inhibitor Drugs 0.000 abstract description 2
- 101150090105 Ezh2 gene Proteins 0.000 abstract description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 102
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 50
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 47
- 150000001721 carbon Chemical group 0.000 description 47
- 125000003386 piperidinyl group Chemical group 0.000 description 47
- 125000002883 imidazolyl group Chemical group 0.000 description 46
- 125000004076 pyridyl group Chemical group 0.000 description 46
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- 125000004193 piperazinyl group Chemical group 0.000 description 41
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- 239000012828 PI3K inhibitor Substances 0.000 description 32
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 15
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
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- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 8
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- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- A61K31/395—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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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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
- A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
- A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Iron Core Of Rotating Electric Machines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
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|---|---|---|---|
| US201662396734P | 2016-09-19 | 2016-09-19 | |
| US201662412720P | 2016-10-25 | 2016-10-25 | |
| PCT/US2017/052086 WO2018053437A1 (en) | 2016-09-19 | 2017-09-18 | Combination therapy |
Publications (1)
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| BR112019005337A2 true BR112019005337A2 (pt) | 2019-08-27 |
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| BR112019005337A BR112019005337A2 (pt) | 2016-09-19 | 2017-09-18 | terapia combinada |
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| US (1) | US20190201409A1 (enExample) |
| EP (1) | EP3515414B1 (enExample) |
| JP (2) | JP2019529419A (enExample) |
| KR (1) | KR20190058550A (enExample) |
| CN (1) | CN109982687A (enExample) |
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| BR (1) | BR112019005337A2 (enExample) |
| CA (1) | CA3037364A1 (enExample) |
| IL (2) | IL292938A (enExample) |
| MA (1) | MA46285A (enExample) |
| MX (1) | MX390121B (enExample) |
| SG (1) | SG10202102845XA (enExample) |
| WO (1) | WO2018053437A1 (enExample) |
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| US20170231986A1 (en) * | 2014-08-11 | 2017-08-17 | Acerta Pharma B.V. | Therapeutic Combinations of a BTK Inhibitor, a PI3K Inhibitor, a JAK-2 Inhibitor, and/or a BCL-2 Inhibitor |
| CN117860758A (zh) | 2017-05-23 | 2024-04-12 | 梅制药公司 | 联合疗法 |
| MX2020001727A (es) | 2017-08-14 | 2020-03-20 | Mei Pharma Inc | Terapia de combinacion. |
| EP3836935A4 (en) * | 2018-08-14 | 2022-09-14 | MEI Pharma, Inc. | TREATMENT OF B LYMPHOCYTE MALIGNITIES |
| JP2021534116A (ja) * | 2018-08-14 | 2021-12-09 | エムイーアイ ファーマ，インク． | 再発性の濾胞性リンパ腫の処置 |
| JP2021534114A (ja) * | 2018-08-14 | 2021-12-09 | エムイーアイ ファーマ，インク． | 併用療法 |
| WO2020132563A1 (en) * | 2018-12-21 | 2020-06-25 | Mei Pharma, Inc. | Combination therapy |
| JP2022514353A (ja) * | 2018-12-21 | 2022-02-10 | ザ ウォルター アンド イライザ ホール インスティテュート オブ メディカル リサーチ | 炎症の治療方法 |
| KR20220164788A (ko) * | 2020-04-07 | 2022-12-13 | 메이 파마, 아이엔씨. | 1,3,5-트리아지닐 벤즈이미다졸의 제조 |
| WO2021252776A1 (en) * | 2020-06-11 | 2021-12-16 | Mei Pharma, Inc. | Combination therapies |
| CN111701026B (zh) * | 2020-06-28 | 2022-10-21 | 吴燕 | 抗肿瘤的组合药物纳米载体及其制备方法 |
| CN118949002A (zh) * | 2024-10-15 | 2024-11-15 | 杭州阿克索生物科技有限责任公司 | 一种宫颈癌细胞抑制组合物及其制备方法和应用 |
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-
2017
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- 2017-09-18 IL IL292938A patent/IL292938A/en unknown
- 2017-09-18 MA MA046285A patent/MA46285A/fr unknown
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- 2017-09-18 US US16/334,303 patent/US20190201409A1/en not_active Abandoned
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| IL265406B (en) | 2022-06-01 |
| EP3515414A4 (en) | 2020-04-01 |
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| IL265406A (en) | 2019-05-30 |
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| AU2017326558A1 (en) | 2019-04-11 |
| SG10202102845XA (en) | 2021-05-28 |
| IL292938A (en) | 2022-07-01 |
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| CA3037364A1 (en) | 2018-03-22 |
| US20190201409A1 (en) | 2019-07-04 |
| EP3515414A1 (en) | 2019-07-31 |
| MX2019003134A (es) | 2019-08-29 |
| MA46285A (fr) | 2019-07-31 |
| EP3515414B1 (en) | 2022-11-30 |
| WO2018053437A1 (en) | 2018-03-22 |
| JP2023001404A (ja) | 2023-01-05 |
| CN109982687A (zh) | 2019-07-05 |
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