CA3132995A1 - Compositions et procedes pour traiter des formes positives de recepteurs des androgenes du cancer - Google Patents
Compositions et procedes pour traiter des formes positives de recepteurs des androgenes du cancer Download PDFInfo
- Publication number
- CA3132995A1 CA3132995A1 CA3132995A CA3132995A CA3132995A1 CA 3132995 A1 CA3132995 A1 CA 3132995A1 CA 3132995 A CA3132995 A CA 3132995A CA 3132995 A CA3132995 A CA 3132995A CA 3132995 A1 CA3132995 A1 CA 3132995A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- methyl
- cancer
- breast cancer
- alkyl
- Prior art date
- 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
Links
- 108010080146 androgen receptors Proteins 0.000 title claims abstract description 161
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 56
- 201000011510 cancer Diseases 0.000 title claims abstract description 28
- 102000001307 androgen receptors Human genes 0.000 title claims abstract description 12
- 238000000034 method Methods 0.000 title claims description 131
- 239000000203 mixture Substances 0.000 title description 62
- 150000001875 compounds Chemical class 0.000 claims abstract description 208
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 79
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 98
- 206010006187 Breast cancer Diseases 0.000 claims description 63
- 208000026310 Breast neoplasm Diseases 0.000 claims description 63
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 62
- 150000003839 salts Chemical class 0.000 claims description 59
- 229910052736 halogen Inorganic materials 0.000 claims description 57
- 150000002367 halogens Chemical class 0.000 claims description 53
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 50
- 206010060862 Prostate cancer Diseases 0.000 claims description 48
- 238000011282 treatment Methods 0.000 claims description 48
- WXCXUHSOUPDCQV-UHFFFAOYSA-N enzalutamide Chemical compound C1=C(F)C(C(=O)NC)=CC=C1N1C(C)(C)C(=O)N(C=2C=C(C(C#N)=CC=2)C(F)(F)F)C1=S WXCXUHSOUPDCQV-UHFFFAOYSA-N 0.000 claims description 38
- 229960004671 enzalutamide Drugs 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims description 23
- 208000022679 triple-negative breast carcinoma Diseases 0.000 claims description 23
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 19
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
- 230000001394 metastastic effect Effects 0.000 claims description 12
- 206010061818 Disease progression Diseases 0.000 claims description 10
- 230000005750 disease progression Effects 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims 4
- 201000007280 estrogen-receptor negative breast cancer Diseases 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract description 29
- 102100032187 Androgen receptor Human genes 0.000 description 149
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 149
- 239000000243 solution Substances 0.000 description 91
- 102100021975 CREB-binding protein Human genes 0.000 description 89
- 108010040163 CREB-Binding Protein Proteins 0.000 description 88
- 229940125904 compound 1 Drugs 0.000 description 69
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 66
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 239000007787 solid Substances 0.000 description 57
- 210000004027 cell Anatomy 0.000 description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 35
- 229940125782 compound 2 Drugs 0.000 description 34
- 230000005764 inhibitory process Effects 0.000 description 34
- 239000003208 petroleum Substances 0.000 description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 32
- 239000012044 organic layer Substances 0.000 description 32
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 239000012043 crude product Substances 0.000 description 30
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 30
- 201000010099 disease Diseases 0.000 description 29
- 102100038885 Histone acetyltransferase p300 Human genes 0.000 description 28
- 101150068427 EP300 gene Proteins 0.000 description 25
- -1 disintigrants Substances 0.000 description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 24
- 229940126214 compound 3 Drugs 0.000 description 23
- 238000010898 silica gel chromatography Methods 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 230000014509 gene expression Effects 0.000 description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 230000001419 dependent effect Effects 0.000 description 20
- 239000000051 antiandrogen Substances 0.000 description 19
- 208000005443 Circulating Neoplastic Cells Diseases 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- 238000009121 systemic therapy Methods 0.000 description 17
- PQRVSWVLDAPYBG-UHFFFAOYSA-N 6-fluoro-2-methyl-5-nitroquinoline Chemical compound [O-][N+](=O)C1=C(F)C=CC2=NC(C)=CC=C21 PQRVSWVLDAPYBG-UHFFFAOYSA-N 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 238000002560 therapeutic procedure Methods 0.000 description 16
- 230000002103 transcriptional effect Effects 0.000 description 16
- 108091005625 BRD4 Proteins 0.000 description 14
- 102100029895 Bromodomain-containing protein 4 Human genes 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- 238000002953 preparative HPLC Methods 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- 230000009467 reduction Effects 0.000 description 13
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 description 12
- 108010081348 HRT1 protein Hairy Proteins 0.000 description 12
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 description 12
- 102100038358 Prostate-specific antigen Human genes 0.000 description 12
- 238000003556 assay Methods 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 230000003442 weekly effect Effects 0.000 description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 11
- 239000003098 androgen Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 230000000259 anti-tumor effect Effects 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 208000030776 invasive breast carcinoma Diseases 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- 208000037821 progressive disease Diseases 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 108020001756 ligand binding domains Proteins 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 8
- 230000002280 anti-androgenic effect Effects 0.000 description 8
- 239000012298 atmosphere Substances 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 101000638154 Homo sapiens Transmembrane protease serine 2 Proteins 0.000 description 7
- GZOSMCIZMLWJML-VJLLXTKPSA-N abiraterone Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CC[C@H](O)CC3=CC2)C)CC[C@@]11C)C=C1C1=CC=CN=C1 GZOSMCIZMLWJML-VJLLXTKPSA-N 0.000 description 7
- 229960000853 abiraterone Drugs 0.000 description 7
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical class C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 7
- 239000002434 gonadorelin derivative Substances 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 230000000955 neuroendocrine Effects 0.000 description 7
- 239000006186 oral dosage form Substances 0.000 description 7
- 230000000750 progressive effect Effects 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 230000000630 rising effect Effects 0.000 description 7
- 230000001629 suppression Effects 0.000 description 7
- 239000003643 water by type Substances 0.000 description 7
- KGJQZPZPVIBTGI-LURJTMIESA-N FC=1C(=C2CC[C@@H](NC2=CC=1)C)[N+](=O)[O-] Chemical compound FC=1C(=C2CC[C@@H](NC2=CC=1)C)[N+](=O)[O-] KGJQZPZPVIBTGI-LURJTMIESA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- FUNVWADXEIGBSD-BFHYXJOUSA-N NC1=C2CC[C@@H](N(C2=CC=C1N[C@H]1C[C@@H](CCC1)C(=O)OC)C(=O)OC)C Chemical compound NC1=C2CC[C@@H](N(C2=CC=C1N[C@H]1C[C@@H](CCC1)C(=O)OC)C(=O)OC)C FUNVWADXEIGBSD-BFHYXJOUSA-N 0.000 description 6
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 6
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000010256 biochemical assay Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 229910052796 boron Inorganic materials 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- 230000009422 growth inhibiting effect Effects 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- QMFDZKBLNVTPMO-BFHYXJOUSA-N methyl (2S)-6-[[(1R,3R)-3-methoxycarbonylcyclohexyl]amino]-2-methyl-5-nitro-3,4-dihydro-2H-quinoline-1-carboxylate Chemical compound COC(=O)[C@H]1C[C@@H](CCC1)NC=1C(=C2CC[C@@H](N(C2=CC=1)C(=O)OC)C)[N+](=O)[O-] QMFDZKBLNVTPMO-BFHYXJOUSA-N 0.000 description 6
- UBEXFVKLUHDRBE-ZETCQYMHSA-N methyl (2S)-6-fluoro-2-methyl-5-nitro-3,4-dihydro-2H-quinoline-1-carboxylate Chemical compound FC=1C(=C2CC[C@@H](N(C2=CC=1)C(=O)OC)C)[N+](=O)[O-] UBEXFVKLUHDRBE-ZETCQYMHSA-N 0.000 description 6
- 239000000825 pharmaceutical preparation Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 230000002194 synthesizing effect Effects 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 101000666295 Homo sapiens X-box-binding protein 1 Proteins 0.000 description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- ZMMITUCIAZVHCG-RNFRBKRXSA-N methyl (1r,3r)-3-aminocyclohexane-1-carboxylate Chemical compound COC(=O)[C@@H]1CCC[C@@H](N)C1 ZMMITUCIAZVHCG-RNFRBKRXSA-N 0.000 description 5
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 235000011181 potassium carbonates Nutrition 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- VXGYRCVTBHVXMZ-UHFFFAOYSA-N quinoline-6-carboxylic acid Chemical compound N1=CC=CC2=CC(C(=O)O)=CC=C21 VXGYRCVTBHVXMZ-UHFFFAOYSA-N 0.000 description 5
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 4
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical class C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 4
- GUZRILZWIBSBAR-UHFFFAOYSA-N 2-(difluoromethoxy)-5-fluorobenzaldehyde Chemical compound FC(F)OC1=CC=C(F)C=C1C=O GUZRILZWIBSBAR-UHFFFAOYSA-N 0.000 description 4
- GPIARMSVZOEZCV-UHFFFAOYSA-N 6-fluoro-2-methylquinoline Chemical compound C1=C(F)C=CC2=NC(C)=CC=C21 GPIARMSVZOEZCV-UHFFFAOYSA-N 0.000 description 4
- LEHFDVYXPCSLJT-UHFFFAOYSA-N 8-chloro-5-methoxy-2-methylquinoline;hydrochloride Chemical compound Cl.CC1=CC=C2C(OC)=CC=C(Cl)C2=N1 LEHFDVYXPCSLJT-UHFFFAOYSA-N 0.000 description 4
- 102000001805 Bromodomains Human genes 0.000 description 4
- 108050009021 Bromodomains Proteins 0.000 description 4
- 239000007821 HATU Substances 0.000 description 4
- 101001091365 Homo sapiens Plasma kallikrein Proteins 0.000 description 4
- 101000605534 Homo sapiens Prostate-specific antigen Proteins 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
- 102100031989 Transmembrane protease serine 2 Human genes 0.000 description 4
- 102100038151 X-box-binding protein 1 Human genes 0.000 description 4
- 230000004075 alteration Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 229910017604 nitric acid Inorganic materials 0.000 description 4
- 108020004017 nuclear receptors Proteins 0.000 description 4
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 4
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- SHNMAZJVVFUXAQ-UHFFFAOYSA-N 2h-quinoline-1-carboxylic acid Chemical compound C1=CC=C2N(C(=O)O)CC=CC2=C1 SHNMAZJVVFUXAQ-UHFFFAOYSA-N 0.000 description 3
- OQPWQOOLGQWRAL-UHFFFAOYSA-N 5-methoxy-2-methylquinoline Chemical compound CC1=CC=C2C(OC)=CC=CC2=N1 OQPWQOOLGQWRAL-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 3
- 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- NVXVOVAJJRGNKH-ZETCQYMHSA-N NC1=C2CC[C@@H](N(C2=CC=C1Br)C(=O)OC)C Chemical compound NC1=C2CC[C@@H](N(C2=CC=C1Br)C(=O)OC)C NVXVOVAJJRGNKH-ZETCQYMHSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 3
- 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000003042 antagnostic effect Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 231100000590 oncogenic Toxicity 0.000 description 3
- 230000002246 oncogenic effect Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- BFYHFIAUSLGNEW-QMMMGPOBSA-N (2S)-5-methoxy-2-methyl-1,2,3,4-tetrahydroquinoline Chemical compound COC1=C2CC[C@@H](NC2=CC=C1)C BFYHFIAUSLGNEW-QMMMGPOBSA-N 0.000 description 2
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- BMTZEAOGFDXDAD-UHFFFAOYSA-M 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium;chloride Chemical compound [Cl-].COC1=NC(OC)=NC([N+]2(C)CCOCC2)=N1 BMTZEAOGFDXDAD-UHFFFAOYSA-M 0.000 description 2
- 229940123407 Androgen receptor antagonist Drugs 0.000 description 2
- XLLDLSDHLNCSEP-SFHVURJKSA-N C1(=CC=CC=C1)C(C1=CC=CC=C1)=NC1=C2CC[C@@H](N(C2=CC=C1)C(=O)OC)C Chemical compound C1(=CC=CC=C1)C(C1=CC=CC=C1)=NC1=C2CC[C@@H](N(C2=CC=C1)C(=O)OC)C XLLDLSDHLNCSEP-SFHVURJKSA-N 0.000 description 2
- JRHNFFAMTPQTOD-VIFPVBQESA-N COC1=C2CC[C@@H](N(C2=CC=C1)C(=O)OC)C Chemical compound COC1=C2CC[C@@H](N(C2=CC=C1)C(=O)OC)C JRHNFFAMTPQTOD-VIFPVBQESA-N 0.000 description 2
- CGGDIKIEHKABSP-QMMMGPOBSA-N C[C@@H]1N(C2=CC=CC(=C2CC1)OS(=O)(=O)C(F)(F)F)C(=O)OC Chemical compound C[C@@H]1N(C2=CC=CC(=C2CC1)OS(=O)(=O)C(F)(F)F)C(=O)OC CGGDIKIEHKABSP-QMMMGPOBSA-N 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 2
- 229910004373 HOAc Inorganic materials 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- XGNZHQFQWFWIQU-QMMMGPOBSA-N NC1=C2CC[C@@H](N(C2=CC=C1)C(=O)OC)C Chemical compound NC1=C2CC[C@@H](N(C2=CC=C1)C(=O)OC)C XGNZHQFQWFWIQU-QMMMGPOBSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- BKOZWHWTXVUTDS-QMMMGPOBSA-N OC1=C2CC[C@@H](N(C2=CC=C1)C(=O)OC)C Chemical compound OC1=C2CC[C@@H](N(C2=CC=C1)C(=O)OC)C BKOZWHWTXVUTDS-QMMMGPOBSA-N 0.000 description 2
- 229940121878 P300 inhibitor Drugs 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 238000012054 celltiter-glo Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 208000027706 hormone receptor-positive breast cancer Diseases 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 238000011474 orchiectomy Methods 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical compound O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000004808 supercritical fluid chromatography Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 2
- 238000000825 ultraviolet detection Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- PAORVUMOXXAMPL-SECBINFHSA-N (2s)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoyl chloride Chemical compound CO[C@](C(Cl)=O)(C(F)(F)F)C1=CC=CC=C1 PAORVUMOXXAMPL-SECBINFHSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- PDVFSPNIEOYOQL-UHFFFAOYSA-N (4-methylphenyl)sulfonyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OS(=O)(=O)C1=CC=C(C)C=C1 PDVFSPNIEOYOQL-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-SSDOTTSWSA-N (R)-mandelic acid Chemical compound OC(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-N 0.000 description 1
- UDVPQRRWUGKGQY-XQHVRGAUSA-N (e)-but-2-enal Chemical compound C\C=C\C=O.C\C=C\C=O UDVPQRRWUGKGQY-XQHVRGAUSA-N 0.000 description 1
- 239000004912 1,5-cyclooctadiene Substances 0.000 description 1
- QRADKVYIJIAENZ-UHFFFAOYSA-N 1-[[bromo(difluoro)methyl]-ethoxyphosphoryl]oxyethane Chemical compound CCOP(=O)(C(F)(F)Br)OCC QRADKVYIJIAENZ-UHFFFAOYSA-N 0.000 description 1
- RIZUCYSQUWMQLX-UHFFFAOYSA-N 2,3-dimethylbenzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1C RIZUCYSQUWMQLX-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- GBOUQGUQUUPGLO-UHFFFAOYSA-N 2-chloro-5-methoxyaniline Chemical compound COC1=CC=C(Cl)C(N)=C1 GBOUQGUQUUPGLO-UHFFFAOYSA-N 0.000 description 1
- FDUBQNUDZOGOFE-UHFFFAOYSA-N 5-fluoro-2-hydroxybenzaldehyde Chemical compound OC1=CC=C(F)C=C1C=O FDUBQNUDZOGOFE-UHFFFAOYSA-N 0.000 description 1
- CRLDWFVRQNUUSZ-UHFFFAOYSA-N 5-fluoro-2-methoxybenzaldehyde Chemical compound COC1=CC=C(F)C=C1C=O CRLDWFVRQNUUSZ-UHFFFAOYSA-N 0.000 description 1
- ZHWAMYZLSLFULC-UHFFFAOYSA-N 9h-imidazo[4,5-f]quinoline Chemical compound C1=CC2=NC=NC2=C2CC=CN=C21 ZHWAMYZLSLFULC-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 108010060434 Co-Repressor Proteins Proteins 0.000 description 1
- 102000008169 Co-Repressor Proteins Human genes 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 102100022893 Histone acetyltransferase KAT5 Human genes 0.000 description 1
- 101710116149 Histone acetyltransferase KAT5 Proteins 0.000 description 1
- 101000896987 Homo sapiens CREB-binding protein Proteins 0.000 description 1
- 101001030211 Homo sapiens Myc proto-oncogene protein Proteins 0.000 description 1
- 101000583175 Homo sapiens Prolactin-inducible protein Proteins 0.000 description 1
- 238000009015 Human TaqMan MicroRNA Assay kit Methods 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 229930182821 L-proline Natural products 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- JSFOGZGIBIQRPU-UHFFFAOYSA-N N-desmethylenzalutamide Chemical compound O=C1C(C)(C)N(C=2C=C(F)C(C(N)=O)=CC=2)C(=S)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 JSFOGZGIBIQRPU-UHFFFAOYSA-N 0.000 description 1
- 238000011789 NOD SCID mouse Methods 0.000 description 1
- 108090001146 Nuclear Receptor Coactivator 1 Proteins 0.000 description 1
- 102100037223 Nuclear receptor coactivator 1 Human genes 0.000 description 1
- 102100030350 Prolactin-inducible protein Human genes 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 108091008771 Rev-ErbA proteins Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 238000003016 alphascreen Methods 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000181 anti-adherent effect Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 239000003911 antiadherent Substances 0.000 description 1
- HJBWBFZLDZWPHF-UHFFFAOYSA-N apalutamide Chemical compound C1=C(F)C(C(=O)NC)=CC=C1N1C2(CCC2)C(=O)N(C=2C=C(C(C#N)=NC=2)C(F)(F)F)C1=S HJBWBFZLDZWPHF-UHFFFAOYSA-N 0.000 description 1
- 229950007511 apalutamide Drugs 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 150000005347 biaryls Chemical class 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- LNAMMBFJMYMQTO-FNEBRGMMSA-N chloroform;(1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].ClC(Cl)Cl.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 LNAMMBFJMYMQTO-FNEBRGMMSA-N 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000005266 circulating tumour cell Anatomy 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000003271 compound fluorescence assay Methods 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 229950001379 darolutamide Drugs 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- WDVGNXKCFBOKDF-UHFFFAOYSA-N dicyclohexyl-[3,6-dimethoxy-2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical compound COC1=CC=C(OC)C(C=2C(=CC(=CC=2C(C)C)C(C)C)C(C)C)=C1P(C1CCCCC1)C1CCCCC1 WDVGNXKCFBOKDF-UHFFFAOYSA-N 0.000 description 1
- IWMMXPNBCHCFCY-UHFFFAOYSA-M dicyclohexyl-[3,6-dimethoxy-2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane;palladium(2+);2-phenylethanamine;chloride Chemical compound [Pd+]Cl.NCCC1=CC=CC=[C-]1.COC1=CC=C(OC)C(C=2C(=CC(=CC=2C(C)C)C(C)C)C(C)C)=C1P(C1CCCCC1)C1CCCCC1 IWMMXPNBCHCFCY-UHFFFAOYSA-M 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 201000007281 estrogen-receptor positive breast cancer Diseases 0.000 description 1
- LHWWETDBWVTKJO-UHFFFAOYSA-N et3n triethylamine Chemical compound CCN(CC)CC.CCN(CC)CC LHWWETDBWVTKJO-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000013100 final test Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 239000007887 hard shell capsule Substances 0.000 description 1
- 229920001903 high density polyethylene Polymers 0.000 description 1
- 239000004700 high-density polyethylene Substances 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 238000009092 lines of therapy Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- OOFXENVWECZJBF-ZJLYAJKPSA-N methyl (1r,3r)-3-aminocyclohexane-1-carboxylate;hydrochloride Chemical compound Cl.COC(=O)[C@@H]1CCC[C@@H](N)C1 OOFXENVWECZJBF-ZJLYAJKPSA-N 0.000 description 1
- ZMMITUCIAZVHCG-NKWVEPMBSA-N methyl (1s,3r)-3-aminocyclohexane-1-carboxylate Chemical compound COC(=O)[C@H]1CCC[C@@H](N)C1 ZMMITUCIAZVHCG-NKWVEPMBSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
- BLIJXOOIHRSQRB-PXYINDEMSA-N n-[(2s)-1-[3-(3-chloro-4-cyanophenyl)pyrazol-1-yl]propan-2-yl]-5-(1-hydroxyethyl)-1h-pyrazole-3-carboxamide Chemical compound C([C@H](C)NC(=O)C=1NN=C(C=1)C(C)O)N(N=1)C=CC=1C1=CC=C(C#N)C(Cl)=C1 BLIJXOOIHRSQRB-PXYINDEMSA-N 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 230000005937 nuclear translocation Effects 0.000 description 1
- 230000005959 oncogenic signaling Effects 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000002331 protein detection Methods 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 1
- 230000025366 tissue development Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Des compositions pharmaceutiques comprenant un composé inhibiteur de CBP peuvent être utilisées pour traiter des patients chez lesquels on a diagnostiqué des formes positives de récepteurs des androgènes du cancer, tels que mCRPC et TNBC, y compris des patients diagnostiqués avec la forme d'épissage AR-v7.
Applications Claiming Priority (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962819472P | 2019-03-15 | 2019-03-15 | |
| US201962819487P | 2019-03-15 | 2019-03-15 | |
| US201962819482P | 2019-03-15 | 2019-03-15 | |
| US201962819490P | 2019-03-15 | 2019-03-15 | |
| US201962819476P | 2019-03-15 | 2019-03-15 | |
| US62/819,482 | 2019-03-15 | ||
| US62/819,490 | 2019-03-15 | ||
| US62/819,472 | 2019-03-15 | ||
| US62/819,487 | 2019-03-15 | ||
| US62/819,476 | 2019-03-15 | ||
| US201962821660P | 2019-03-21 | 2019-03-21 | |
| US62/821,660 | 2019-03-21 | ||
| PCT/US2019/039936 WO2020006483A1 (fr) | 2018-06-29 | 2019-06-28 | Inhibition de la protéine de liaison à creb (cbp) |
| USPCT/US2019/039936 | 2019-06-28 | ||
| PCT/US2020/022823 WO2020190792A1 (fr) | 2019-03-15 | 2020-03-13 | Compositions et procédés pour traiter des formes positives de récepteurs des androgènes du cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3132995A1 true CA3132995A1 (fr) | 2020-09-24 |
Family
ID=72521203
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3132995A Pending CA3132995A1 (fr) | 2019-03-15 | 2020-03-13 | Compositions et procedes pour traiter des formes positives de recepteurs des androgenes du cancer |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP3938365A4 (fr) |
| CN (1) | CN113784967A (fr) |
| AU (1) | AU2020241709A1 (fr) |
| BR (1) | BR112021018266A2 (fr) |
| CA (1) | CA3132995A1 (fr) |
| MX (1) | MX2021011154A (fr) |
| WO (1) | WO2020190792A1 (fr) |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010110380A1 (fr) * | 2009-03-27 | 2010-09-30 | 興和株式会社 | Composé de pipéridine condensé et agent pharmaceutique le contenant |
| CN103038229B (zh) * | 2010-05-26 | 2016-05-11 | 桑诺维恩药品公司 | 杂芳基化合物及其使用方法 |
| MX370535B (es) * | 2013-11-18 | 2019-12-17 | Forma Therapeutics Inc | Compuestos de tetrahidroquinolina como inhibidores del bromodominio extra terminal y bromo (bet) y el uso de los mismos en el tratamiento de cáncer. |
| EP3632915A1 (fr) * | 2014-11-27 | 2020-04-08 | Genentech, Inc. | Composés 4,5,6,7-tetrahydro-1 h-pyrazolo[4,3-c]pyridin-3-amine utilisés comme inhibiteurs de cbp et/ou de ep300 |
| WO2017197056A1 (fr) * | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | Dégronimères ciblant un bromodomaine pour la dégradation de protéines cibles |
| EP3681885B1 (fr) * | 2017-09-15 | 2024-02-28 | Forma Therapeutics, Inc. | Compositions de tétrahydroimidazo quinoléine utilisées en tant qu'inhibiteurs de cbp/p300 |
| MX2023013508A (es) * | 2018-06-29 | 2023-12-13 | Forma Therapeutics Inc | Inhibicion de la proteina de union a creb (cbp). |
-
2020
- 2020-03-13 EP EP20774663.7A patent/EP3938365A4/fr active Pending
- 2020-03-13 BR BR112021018266A patent/BR112021018266A2/pt unknown
- 2020-03-13 AU AU2020241709A patent/AU2020241709A1/en active Pending
- 2020-03-13 MX MX2021011154A patent/MX2021011154A/es unknown
- 2020-03-13 CA CA3132995A patent/CA3132995A1/fr active Pending
- 2020-03-13 WO PCT/US2020/022823 patent/WO2020190792A1/fr unknown
- 2020-03-13 CN CN202080021617.5A patent/CN113784967A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP3938365A4 (fr) | 2023-01-25 |
| CN113784967A (zh) | 2021-12-10 |
| WO2020190792A1 (fr) | 2020-09-24 |
| EP3938365A1 (fr) | 2022-01-19 |
| BR112021018266A2 (pt) | 2022-02-01 |
| AU2020241709A1 (en) | 2021-09-23 |
| MX2021011154A (es) | 2021-10-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2020341681B2 (en) | RIP1 inhibitory compounds and methods for making and using the same | |
| JP2020200308A (ja) | Ｎａｓｈ／ｎａｆｌｄおよび関連疾患治療のための組合せ | |
| KR20160146807A (ko) | Ｉｄｏ１ 억제제로서 사용하기 위한 피롤리딘-２,５-디온 유도체, 제약 조성물 및 방법 | |
| EP3713923B1 (fr) | 2-phénylpyrimidine-4-carboxamides à utiliser en tant qu'inhibiteurs d'ahr | |
| EA025837B1 (ru) | Замещенные аннеллированные пиримидины и триазины | |
| US10870648B2 (en) | Inhibiting CREB binding protein (CBP) | |
| US11203597B2 (en) | Crystalline spirocyclic compound, a dosage form containing, a method for using in treatment of disease, and a method for recrystallizing | |
| TW201920169A (zh) | 作為ＣＢＰ／ｐ３００抑制劑之四氫─咪唑並喹啉化合物 | |
| WO2020224652A1 (fr) | Inhibiteurs de protéase spécifiques de l'ubiquitine, leur procédé de préparation et leur application | |
| CN104619327A (zh) | 作为激酶抑制剂的氨基喹唑啉的前药 | |
| JP2023524361A (ja) | Ｔｙｋ２活性を阻害する複素環式化合物 | |
| WO2018080216A1 (fr) | Dérivé de phénylphtalazine, sa méthode de préparation et composition pharmaceutique le comprenant | |
| KR102097878B1 (ko) | 디아미노 피리딘 유도체 | |
| AU2011318875A1 (en) | Antagonist for mutated androgen receptor | |
| EP3197452B1 (fr) | Inhibiteurs de la hif prolyl hydroxylase | |
| CA3132995A1 (fr) | Compositions et procedes pour traiter des formes positives de recepteurs des androgenes du cancer | |
| JP2022500456A (ja) | キナゾリン化合物及びその塩酸塩の結晶形 | |
| RU2817802C2 (ru) | Композиции и способы лечения андроген-рецептор-положительных форм рака | |
| AU2022340664A1 (en) | Novel ras inhibitors | |
| US6673809B2 (en) | Tricyclic compounds as MRP1-inhibitors | |
| AU2015386039B2 (en) | Bicyclic pyridine compound | |
| US11801243B2 (en) | Bromodomain inhibitors for androgen receptor-driven cancers | |
| TWI846350B (zh) | 作為ＣＢＰ／ｐ３００抑制劑之四氫－咪唑並喹啉化合物 | |
| EP3484852A1 (fr) | Composés de benzo-n-hydroxy amide ayant une activité antitumorale | |
| EA042920B1 (ru) | Ингибирование creb-связывающего белка (cbp) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20231016 |
|
| EEER | Examination request |
Effective date: 20231016 |
|
| EEER | Examination request |
Effective date: 20231016 |