CA3215379A1 - Substituted spiro derivatives - Google Patents

Substituted spiro derivatives Download PDF

Info

Publication number: CA3215379A1
Authority: CA; Canada
Prior art keywords: 4alkyl; group; compound; substituted; mmol
Prior art date: 2021-05-08
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Pending

Application number

CA3215379A

Other languages

English (en)

French (fr)

Inventor

Olivier Alexis Georges Querolle

Xuedong Dai

Wei Cai

Johannes Wilhelmus J. Thuring

Lichao FANG

Ming Li

Lianzhu LIU

Yingtao LIU

Luoheng QIN

Jianping Wu

Yanping Xu

Patrick Rene Angibaud

Helene France Solange Colombel

Isabelle Noelle Constance Pilatte

Virginie Sophie Poncelet

Carsten Sven KRAMER

Vineet PANDE

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Janssen Pharmaceutica NV

Original Assignee

Janssen Pharmaceutica NV

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2021-05-08

Filing date

2022-05-06

Publication date

2022-11-17

2022-05-06 Application filed by Janssen Pharmaceutica NV filed Critical Janssen Pharmaceutica NV

2022-11-17 Publication of CA3215379A1 publication Critical patent/CA3215379A1/en

Status Pending legal-status Critical Current

Links

125000003003 spiro group Chemical group 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 327
206010028980 Neoplasm Diseases 0.000 claims abstract description 32
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
201000011510 cancer Diseases 0.000 claims abstract description 24
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
201000003793 Myelodysplastic syndrome Diseases 0.000 claims abstract description 15
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 144
229910052757 nitrogen Inorganic materials 0.000 claims description 136
125000001424 substituent group Chemical group 0.000 claims description 105
150000003839 salts Chemical class 0.000 claims description 81
125000004433 nitrogen atom Chemical group N* 0.000 claims description 73
238000000034 method Methods 0.000 claims description 70
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 68
239000012453 solvate Substances 0.000 claims description 65
125000005842 heteroatom Chemical group 0.000 claims description 61
229910052717 sulfur Inorganic materials 0.000 claims description 60
125000002950 monocyclic group Chemical group 0.000 claims description 44
229910052799 carbon Inorganic materials 0.000 claims description 43
125000005843 halogen group Chemical group 0.000 claims description 43
-1 -OH Chemical group 0.000 claims description 41
229910052739 hydrogen Inorganic materials 0.000 claims description 39
239000001257 hydrogen Substances 0.000 claims description 39
125000004434 sulfur atom Chemical group 0.000 claims description 39
125000004432 carbon atom Chemical group C* 0.000 claims description 35
208000032839 leukemia Diseases 0.000 claims description 35
238000011282 treatment Methods 0.000 claims description 30
125000004093 cyano group Chemical group *C#N 0.000 claims description 28
125000002619 bicyclic group Chemical group 0.000 claims description 26
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 18
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
125000003118 aryl group Chemical group 0.000 claims description 17
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
229920006395 saturated elastomer Polymers 0.000 claims description 16
230000002265 prevention Effects 0.000 claims description 14
230000014509 gene expression Effects 0.000 claims description 13
150000002431 hydrogen Chemical class 0.000 claims description 12
208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 9
239000003814 drug Substances 0.000 claims description 9
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
208000035475 disorder Diseases 0.000 claims description 7
206010000830 Acute leukaemia Diseases 0.000 claims description 6
208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 6
208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 6
208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 6
208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 6
208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 6
208000033759 Prolymphocytic T-Cell Leukemia Diseases 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
201000009277 hairy cell leukemia Diseases 0.000 claims description 6
208000003747 lymphoid leukemia Diseases 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
229910052731 fluorine Inorganic materials 0.000 claims description 5
125000003226 pyrazolyl group Chemical group 0.000 claims description 5
206010060862 Prostate cancer Diseases 0.000 claims description 4
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
125000001425 triazolyl group Chemical group 0.000 claims description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
206010006187 Breast cancer Diseases 0.000 claims description 3
208000026310 Breast neoplasm Diseases 0.000 claims description 3
206010009944 Colon cancer Diseases 0.000 claims description 3
208000006404 Large Granular Lymphocytic Leukemia Diseases 0.000 claims description 3
206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
201000008717 T-cell large granular lymphocyte leukemia Diseases 0.000 claims description 3
230000001154 acute effect Effects 0.000 claims description 3
208000024207 chronic leukemia Diseases 0.000 claims description 3
208000029742 colonic neoplasm Diseases 0.000 claims description 3
208000005017 glioblastoma Diseases 0.000 claims description 3
201000007270 liver cancer Diseases 0.000 claims description 3
208000014018 liver neoplasm Diseases 0.000 claims description 3
201000005202 lung cancer Diseases 0.000 claims description 3
208000020816 lung neoplasm Diseases 0.000 claims description 3
208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
201000001441 melanoma Diseases 0.000 claims description 3
208000025113 myeloid leukemia Diseases 0.000 claims description 3
201000000050 myeloid neoplasm Diseases 0.000 claims description 3
201000002528 pancreatic cancer Diseases 0.000 claims description 3
208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
101100070530 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) het-6 gene Proteins 0.000 claims description 2
230000001747 exhibiting effect Effects 0.000 claims description 2
101150084750 1 gene Proteins 0.000 claims 1
101100118680 Caenorhabditis elegans sec-61.G gene Proteins 0.000 claims 1
125000000217 alkyl group Chemical group 0.000 claims 1
101710169972 Menin Proteins 0.000 abstract description 41
102100030550 Menin Human genes 0.000 abstract description 41
102100022103 Histone-lysine N-methyltransferase 2A Human genes 0.000 abstract description 31
101001045846 Homo sapiens Histone-lysine N-methyltransferase 2A Proteins 0.000 abstract description 31
201000010099 disease Diseases 0.000 abstract description 18
239000003112 inhibitor Substances 0.000 abstract description 15
241000124008 Mammalia Species 0.000 abstract description 6
230000006916 protein interaction Effects 0.000 abstract description 6
239000008177 pharmaceutical agent Substances 0.000 abstract description 5
238000011321 prophylaxis Methods 0.000 abstract description 2
238000002560 therapeutic procedure Methods 0.000 abstract description 2
239000000543 intermediate Substances 0.000 description 354
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 339
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 274
239000000203 mixture Substances 0.000 description 192
238000002360 preparation method Methods 0.000 description 144
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 137
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 134
239000012071 phase Substances 0.000 description 133
239000000243 solution Substances 0.000 description 131
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 111
239000011541 reaction mixture Substances 0.000 description 91
239000007787 solid Substances 0.000 description 87
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 74
239000012044 organic layer Substances 0.000 description 71
230000002829 reductive effect Effects 0.000 description 71
239000002904 solvent Substances 0.000 description 70
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 67
238000006243 chemical reaction Methods 0.000 description 65
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 59
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 52
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 48
239000000047 product Substances 0.000 description 48
239000012267 brine Substances 0.000 description 47
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 47
238000003756 stirring Methods 0.000 description 47
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 46
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 40
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
239000007832 Na2SO4 Substances 0.000 description 39
229910052938 sodium sulfate Inorganic materials 0.000 description 39
235000011152 sodium sulphate Nutrition 0.000 description 39
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 37
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 37
235000012538 ammonium bicarbonate Nutrition 0.000 description 37
235000011114 ammonium hydroxide Nutrition 0.000 description 37
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
210000004027 cell Anatomy 0.000 description 33
229910052943 magnesium sulfate Inorganic materials 0.000 description 33
235000019341 magnesium sulphate Nutrition 0.000 description 33
230000005526 G1 to G0 transition Effects 0.000 description 32
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 30
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
239000002585 base Substances 0.000 description 27
239000000741 silica gel Substances 0.000 description 26
229910002027 silica gel Inorganic materials 0.000 description 26
239000001569 carbon dioxide Substances 0.000 description 25
229910002092 carbon dioxide Inorganic materials 0.000 description 25
108090000623 proteins and genes Proteins 0.000 description 24
238000010898 silica gel chromatography Methods 0.000 description 24
239000000706 filtrate Substances 0.000 description 23
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 22
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
239000003921 oil Substances 0.000 description 22
239000003480 eluent Substances 0.000 description 21
238000002953 preparative HPLC Methods 0.000 description 21
238000004808 supercritical fluid chromatography Methods 0.000 description 21
IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 20
229940125807 compound 37 Drugs 0.000 description 20
239000012043 crude product Substances 0.000 description 20
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 19
230000001788 irregular Effects 0.000 description 19
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
230000003993 interaction Effects 0.000 description 18
239000007858 starting material Substances 0.000 description 18
239000000843 powder Substances 0.000 description 17
239000003643 water by type Substances 0.000 description 17
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 16
229910020175 SiOH Inorganic materials 0.000 description 16
239000002253 acid Substances 0.000 description 16
FYCBRGMZDWYEHI-UHFFFAOYSA-N oxetane-3-carbaldehyde Chemical compound O=CC1COC1 FYCBRGMZDWYEHI-UHFFFAOYSA-N 0.000 description 16
238000000746 purification Methods 0.000 description 16
229940086542 triethylamine Drugs 0.000 description 16
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 15
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 15
239000007864 aqueous solution Substances 0.000 description 14
239000010410 layer Substances 0.000 description 14
229910000027 potassium carbonate Inorganic materials 0.000 description 14
239000000523 sample Substances 0.000 description 14
125000004429 atom Chemical group 0.000 description 13
UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 13
102000004169 proteins and genes Human genes 0.000 description 13
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 description 12
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 12
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 12
150000001721 carbon Chemical group 0.000 description 12
108020001507 fusion proteins Proteins 0.000 description 12
102000037865 fusion proteins Human genes 0.000 description 12
235000015320 potassium carbonate Nutrition 0.000 description 12
239000011369 resultant mixture Substances 0.000 description 12
235000017557 sodium bicarbonate Nutrition 0.000 description 12
229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 11
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
229910000024 caesium carbonate Inorganic materials 0.000 description 10
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 10
238000002868 homogeneous time resolved fluorescence Methods 0.000 description 10
239000005457 ice water Substances 0.000 description 10
230000014759 maintenance of location Effects 0.000 description 10
239000012047 saturated solution Substances 0.000 description 10
238000012360 testing method Methods 0.000 description 10
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 9
229910052771 Terbium Inorganic materials 0.000 description 9
238000003556 assay Methods 0.000 description 9
235000011089 carbon dioxide Nutrition 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
239000011734 sodium Substances 0.000 description 9
GZCRRIHWUXGPOV-UHFFFAOYSA-N terbium atom Chemical compound [Tb] GZCRRIHWUXGPOV-UHFFFAOYSA-N 0.000 description 9
101150041968 CDC13 gene Proteins 0.000 description 8
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 8
101150029107 MEIS1 gene Proteins 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
239000003795 chemical substances by application Substances 0.000 description 8
238000001914 filtration Methods 0.000 description 8
238000003818 flash chromatography Methods 0.000 description 8
IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 8
229910052763 palladium Inorganic materials 0.000 description 8
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 8
229910052708 sodium Inorganic materials 0.000 description 8
229910000029 sodium carbonate Inorganic materials 0.000 description 8
239000000126 substance Substances 0.000 description 8
241000282414 Homo sapiens Species 0.000 description 7
102000047831 Myeloid Ecotropic Viral Integration Site 1 Human genes 0.000 description 7
108700041619 Myeloid Ecotropic Viral Integration Site 1 Proteins 0.000 description 7
238000005481 NMR spectroscopy Methods 0.000 description 7
GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 7
238000011534 incubation Methods 0.000 description 7
230000002246 oncogenic effect Effects 0.000 description 7
125000006239 protecting group Chemical group 0.000 description 7
230000002441 reversible effect Effects 0.000 description 7
239000012279 sodium borohydride Substances 0.000 description 7
229910000033 sodium borohydride Inorganic materials 0.000 description 7
230000001225 therapeutic effect Effects 0.000 description 7
238000004704 ultra performance liquid chromatography Methods 0.000 description 7
ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 6
PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 6
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 6
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
229940127271 compound 49 Drugs 0.000 description 6
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
239000000284 extract Substances 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000012299 nitrogen atmosphere Substances 0.000 description 6
231100000590 oncogenic Toxicity 0.000 description 6
238000000926 separation method Methods 0.000 description 6
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238000001640 fractional crystallisation Methods 0.000 description 1
KQGXYVJZOMKLSA-UHFFFAOYSA-N furo[2,3-d]pyrimidine Chemical compound N1=CN=C2OC=CC2=C1 KQGXYVJZOMKLSA-UHFFFAOYSA-N 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000000499 gel Substances 0.000 description 1
230000004547 gene signature Effects 0.000 description 1
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
230000003394 haemopoietic effect Effects 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
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150000002367 halogens Chemical class 0.000 description 1
201000005787 hematologic cancer Diseases 0.000 description 1
208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
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150000004677 hydrates Chemical class 0.000 description 1
USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
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QRUDPBHCPMSJFN-UHFFFAOYSA-M magnesium;cyclobutane;bromide Chemical compound [Mg+2].[Br-].C1C[CH-]C1 QRUDPBHCPMSJFN-UHFFFAOYSA-M 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
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VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
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238000012986 modification Methods 0.000 description 1
239000003607 modifier Substances 0.000 description 1
230000009456 molecular mechanism Effects 0.000 description 1
DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
210000004898 n-terminal fragment Anatomy 0.000 description 1
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150000007524 organic acids Chemical class 0.000 description 1
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URUUZIAJVSGYRC-UHFFFAOYSA-N oxan-3-one Chemical compound O=C1CCCOC1 URUUZIAJVSGYRC-UHFFFAOYSA-N 0.000 description 1
JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000003566 oxetanyl group Chemical group 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
JLPJFSCQKHRSQR-UHFFFAOYSA-N oxolan-3-one Chemical compound O=C1CCOC1 JLPJFSCQKHRSQR-UHFFFAOYSA-N 0.000 description 1
239000001301 oxygen Chemical group 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
230000007170 pathology Effects 0.000 description 1
235000019371 penicillin G benzathine Nutrition 0.000 description 1
239000000816 peptidomimetic Chemical class 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
238000005191 phase separation Methods 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
DBMHTLOVZSDLFD-UHFFFAOYSA-N piperidin-1-ylmethanamine Chemical class NCN1CCCCC1 DBMHTLOVZSDLFD-UHFFFAOYSA-N 0.000 description 1
RJUAEBLXGFKZMS-UHFFFAOYSA-N piperidin-1-ylmethanol Chemical compound OCN1CCCCC1 RJUAEBLXGFKZMS-UHFFFAOYSA-N 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
229920001992 poloxamer 407 Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
230000036515 potency Effects 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
230000000644 propagated effect Effects 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 1
238000011002 quantification Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
150000003248 quinolines Chemical class 0.000 description 1
SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
239000013557 residual solvent Substances 0.000 description 1
238000012552 review Methods 0.000 description 1
102220298895 rs1025502215 Human genes 0.000 description 1
238000009738 saturating Methods 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
238000010956 selective crystallization Methods 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 1
210000000130 stem cell Anatomy 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
150000001420 substituted heterocyclic compounds Chemical class 0.000 description 1
239000000758 substrate Substances 0.000 description 1
229960005137 succinic acid Drugs 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
230000006103 sulfonylation Effects 0.000 description 1
238000005694 sulfonylation reaction Methods 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
238000011361 targeted radionuclide therapy Methods 0.000 description 1
230000008685 targeting Effects 0.000 description 1
AUMRFKQAZLPMFC-UHFFFAOYSA-N tert-butyl 3-(2-methylpropanoyl)azetidine-1-carboxylate Chemical compound CC(C)C(=O)C1CN(C(=O)OC(C)(C)C)C1 AUMRFKQAZLPMFC-UHFFFAOYSA-N 0.000 description 1
KZBWIYHDNQHMET-UHFFFAOYSA-N tert-butyl 4-bromopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(Br)CC1 KZBWIYHDNQHMET-UHFFFAOYSA-N 0.000 description 1
150000003510 tertiary aliphatic amines Chemical class 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
208000016595 therapy related acute myeloid leukemia and myelodysplastic syndrome Diseases 0.000 description 1
SMZMHUCIDGHERP-UHFFFAOYSA-N thieno[2,3-b]pyridine Chemical compound C1=CN=C2SC=CC2=C1 SMZMHUCIDGHERP-UHFFFAOYSA-N 0.000 description 1
DDWBRNXDKNIQDY-UHFFFAOYSA-N thieno[2,3-d]pyrimidine Chemical class N1=CN=C2SC=CC2=C1 DDWBRNXDKNIQDY-UHFFFAOYSA-N 0.000 description 1
125000002053 thietanyl group Chemical group 0.000 description 1
125000001166 thiolanyl group Chemical group 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
238000003354 tissue distribution assay Methods 0.000 description 1
238000004448 titration Methods 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
230000002103 transcriptional effect Effects 0.000 description 1
230000005945 translocation Effects 0.000 description 1
WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
238000007514 turning Methods 0.000 description 1
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- 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
- C07D487/10—Spiro-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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- 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
- C07D471/10—Spiro-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Diabetes (AREA)
Hematology (AREA)
Epidemiology (AREA)
Endocrinology (AREA)
Emergency Medicine (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Obesity (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

CA3215379A 2021-05-08 2022-05-06 Substituted spiro derivatives Pending CA3215379A1 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
CN2021092256		2021-05-08
CNPCT/CN2021/092256		2021-05-08
PCT/CN2022/091065 WO2022237626A1 (en)	2021-05-08	2022-05-06	Substituted spiro derivatives

Publications (1)

Publication Number	Publication Date
CA3215379A1 true CA3215379A1 (en)	2022-11-17

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ID=76159225

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA3215379A Pending CA3215379A1 (en)	2021-05-08	2022-05-06	Substituted spiro derivatives

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EP (1)	EP4334310A1 (pt)
JP (1)	JP2024518434A (pt)
KR (1)	KR20240006542A (pt)
CN (1)	CN117321049A (pt)
AU (1)	AU2022272692A1 (pt)
BR (1)	BR112023023154A2 (pt)
CA (1)	CA3215379A1 (pt)
WO (1)	WO2022237626A1 (pt)

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CN105188705A (zh)	2013-03-13	2015-12-23	密歇根大学董事会	包含噻吩并嘧啶和噻吩并吡啶化合物的组合物及其使用方法
USRE49687E1 (en)	2014-09-09	2023-10-10	The Regents Of The University Of Michigan	Thienopyrimidine and thienopyridine compounds and methods of use thereof
AR104020A1 (es)	2015-06-04	2017-06-21	Kura Oncology Inc	Métodos y composiciones para inhibir la interacción de menina con proteínas mill
WO2016197027A1 (en)	2015-06-04	2016-12-08	Kura Oncology, Inc.	Methods and compositions for inhibiting the interaction of menin with mll proteins
EP3394064A1 (en)	2015-12-22	2018-10-31	Vitae Pharmaceuticals, Inc.	Inhibitors of the menin-mll interaction
JP7000333B2 (ja)	2016-03-16	2022-02-10	クラオンコロジー，インク．	メニン－ｍｌｌの架橋された二環式阻害剤及びその使用方法
HRP20230537T1 (hr)	2016-03-16	2023-08-04	Kura Oncology, Inc.	Supstituirani derivati tieno[2,3-d]pirimidina kao inhibitori za menin-mll i postupci za uporabu
CN109415337B (zh)	2016-05-02	2022-01-18	密执安大学评议会	作为多发性内分泌腺瘤蛋白抑制剂的哌啶
WO2017207387A1 (en)	2016-05-31	2017-12-07	Bayer Pharma Aktiengesellschaft	Spiro condensed azetidine derivatives as inhibitors of the menin-mml1 interaction
ES2831084T3 (es)	2016-06-10	2021-06-07	Vitae Pharmaceuticals Inc	Inhibidores de la interacción menina-MLL
WO2018024602A1 (en)	2016-08-04	2018-02-08	Bayer Aktiengesellschaft	2,7-diazaspiro[4.4]nonanes
CA3033239A1 (en)	2016-09-14	2018-03-22	Janssen Pharmaceutica Nv	Spiro bicyclic inhibitors of menin-mll interaction
AU2017326485B2 (en)	2016-09-14	2021-04-22	Janssen Pharmaceutica Nv	Fused bicyclic inhibitors of menin-MLL interaction
MX2019003091A (es)	2016-09-16	2019-07-08	Vitae Pharmaceuticals Inc	Inhibidores de la interaccion de menina-mll.
WO2018109088A1 (en)	2016-12-15	2018-06-21	Janssen Pharmaceutica Nv	Azepane inhibitors of menin-mll interaction
EP3601249A4 (en)	2017-03-24	2020-12-16	Kura Oncology, Inc.	METHODS OF TREATMENT OF MALIGNANT HEMOPATHIES AND EWING'S SARCOMA
US11542248B2 (en)	2017-06-08	2023-01-03	Kura Oncology, Inc.	Methods and compositions for inhibiting the interaction of menin with MLL proteins
TW201920170A (zh)	2017-09-20	2019-06-01	美商庫拉腫瘤技術股份有限公司	經取代之menin-mll 抑制劑及使用方法
MX2020006594A (es)	2017-12-20	2020-09-09	Janssen Pharmaceutica Nv	Inhibidores de exo-azaespiro de la interaccion menina-mll.
US11369605B2 (en)	2018-08-27	2022-06-28	Sumitomo Dainippon Pharma Co., Ltd.	Optically active azabicyclo ring derivative
WO2020069027A1 (en)	2018-09-26	2020-04-02	Kura Oncology, Inc.	Treatment of hematological malignancies with inhibitors of menin
EP4077312A4 (en)	2019-12-19	2024-01-17	Janssen Pharmaceutica Nv	SUBSTITUTED STRAIGHT CHAIN SPIRO DERIVATIVES
CN111297863B (zh)	2020-03-30	2021-06-25	四川大学华西医院	menin-MLL抑制剂在制备治疗子宫内膜癌的药物中的应用

2022
- 2022-05-06 WO PCT/CN2022/091065 patent/WO2022237626A1/en active Application Filing
- 2022-05-06 KR KR1020237038500A patent/KR20240006542A/ko unknown
- 2022-05-06 JP JP2023568501A patent/JP2024518434A/ja active Pending
- 2022-05-06 AU AU2022272692A patent/AU2022272692A1/en active Pending
- 2022-05-06 CA CA3215379A patent/CA3215379A1/en active Pending
- 2022-05-06 CN CN202280033667.4A patent/CN117321049A/zh active Pending
- 2022-05-06 EP EP22725155.0A patent/EP4334310A1/en active Pending
- 2022-05-06 BR BR112023023154A patent/BR112023023154A2/pt unknown

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Publication number	Publication date
BR112023023154A2 (pt)	2024-01-23
KR20240006542A (ko)	2024-01-15
AU2022272692A1 (en)	2024-01-04
EP4334310A1 (en)	2024-03-13
WO2022237626A1 (en)	2022-11-17
JP2024518434A (ja)	2024-05-01
CN117321049A (zh)	2023-12-29

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