CA2903473A1 - Histone demethylase inhibitors - Google Patents
Histone demethylase inhibitors Download PDFInfo
- Publication number
- CA2903473A1 CA2903473A1 CA2903473A CA2903473A CA2903473A1 CA 2903473 A1 CA2903473 A1 CA 2903473A1 CA 2903473 A CA2903473 A CA 2903473A CA 2903473 A CA2903473 A CA 2903473A CA 2903473 A1 CA2903473 A1 CA 2903473A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- pyridine
- pyrrolo
- formula
- embodiment provides
- 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.)
- Abandoned
Links
- 108010074870 Histone Demethylases Proteins 0.000 title claims abstract description 22
- 102000008157 Histone Demethylases Human genes 0.000 title claims abstract description 22
- 239000003112 inhibitor Substances 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 566
- 238000000034 method Methods 0.000 claims abstract description 166
- 239000000203 mixture Substances 0.000 claims abstract description 35
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 19
- 201000011510 cancer Diseases 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Chemical class 0.000 claims abstract description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 116
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 109
- 125000000217 alkyl group Chemical group 0.000 claims description 108
- 125000001072 heteroaryl group Chemical group 0.000 claims description 75
- 125000000623 heterocyclic group Chemical group 0.000 claims description 75
- 125000003118 aryl group Chemical group 0.000 claims description 70
- 150000003839 salts Chemical class 0.000 claims description 46
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 29
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000003282 alkyl amino group Chemical group 0.000 claims description 16
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 16
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical group 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 150000001204 N-oxides Chemical class 0.000 claims description 3
- -1 pyrrolopyridine derivative compounds Chemical class 0.000 abstract description 248
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 14
- 201000010099 disease Diseases 0.000 abstract description 11
- 230000005764 inhibitory process Effects 0.000 abstract description 10
- 238000011282 treatment Methods 0.000 abstract description 8
- 206010006187 Breast cancer Diseases 0.000 abstract description 7
- 208000026310 Breast neoplasm Diseases 0.000 abstract description 7
- 206010005003 Bladder cancer Diseases 0.000 abstract description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 abstract description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 abstract description 5
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 abstract description 5
- 201000005202 lung cancer Diseases 0.000 abstract description 5
- 208000020816 lung neoplasm Diseases 0.000 abstract description 5
- 201000005112 urinary bladder cancer Diseases 0.000 abstract description 5
- 206010060862 Prostate cancer Diseases 0.000 abstract description 4
- 201000001441 melanoma Diseases 0.000 abstract description 4
- 230000001613 neoplastic effect Effects 0.000 abstract description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 184
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 147
- 238000002360 preparation method Methods 0.000 description 145
- 238000005160 1H NMR spectroscopy Methods 0.000 description 140
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 78
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 64
- 239000000126 substance Substances 0.000 description 52
- 238000006243 chemical reaction Methods 0.000 description 48
- YBYWIZUWOGPUPB-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound OC(=O)C1=CC=NC2=C1NC=C2 YBYWIZUWOGPUPB-UHFFFAOYSA-N 0.000 description 46
- 101150041968 CDC13 gene Proteins 0.000 description 41
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 41
- 238000003786 synthesis reaction Methods 0.000 description 39
- 230000015572 biosynthetic process Effects 0.000 description 36
- 150000007942 carboxylates Chemical class 0.000 description 33
- 125000004432 carbon atom Chemical group C* 0.000 description 32
- 150000003254 radicals Chemical class 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 27
- 101001088893 Homo sapiens Lysine-specific demethylase 4C Proteins 0.000 description 26
- 102100033230 Lysine-specific demethylase 4C Human genes 0.000 description 25
- 108010033040 Histones Proteins 0.000 description 24
- 101000613625 Homo sapiens Lysine-specific demethylase 4A Proteins 0.000 description 24
- 102100040863 Lysine-specific demethylase 4A Human genes 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 238000003556 assay Methods 0.000 description 21
- 239000002253 acid Substances 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 17
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 16
- 125000001424 substituent group Chemical group 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 101000615488 Homo sapiens Methyl-CpG-binding domain protein 2 Proteins 0.000 description 15
- 102100021299 Methyl-CpG-binding domain protein 2 Human genes 0.000 description 15
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 15
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 125000003710 aryl alkyl group Chemical group 0.000 description 14
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 14
- 238000001514 detection method Methods 0.000 description 13
- 125000003709 fluoroalkyl group Chemical group 0.000 description 13
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 13
- 239000000651 prodrug Substances 0.000 description 13
- 229940002612 prodrug Drugs 0.000 description 13
- 102000006947 Histones Human genes 0.000 description 12
- 102100033247 Lysine-specific demethylase 5B Human genes 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 244000201986 Cassia tora Species 0.000 description 11
- 101001088883 Homo sapiens Lysine-specific demethylase 5B Proteins 0.000 description 11
- 125000004450 alkenylene group Chemical group 0.000 description 11
- 125000005884 carbocyclylalkyl group Chemical group 0.000 description 11
- NCAIGTHBQTXTLR-UHFFFAOYSA-N phentermine hydrochloride Chemical compound [Cl-].CC(C)([NH3+])CC1=CC=CC=C1 NCAIGTHBQTXTLR-UHFFFAOYSA-N 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- VCUDZTCDUDDJGG-UHFFFAOYSA-N 1-(1'-{[3-(methylsulfanyl)-2-benzothiophen-1-yl]carbonyl}spiro[1-benzofuran-3,4'-piperidin]-5-yl)methanamine Chemical compound C1=CC=CC2=C(SC)SC(C(=O)N3CCC4(C5=CC(CN)=CC=C5OC4)CC3)=C21 VCUDZTCDUDDJGG-UHFFFAOYSA-N 0.000 description 10
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 10
- 101001088892 Homo sapiens Lysine-specific demethylase 5A Proteins 0.000 description 10
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 10
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 125000004122 cyclic group Chemical group 0.000 description 10
- 125000005843 halogen group Chemical group 0.000 description 10
- 235000018977 lysine Nutrition 0.000 description 10
- 238000007069 methylation reaction Methods 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 9
- 239000004472 Lysine Substances 0.000 description 9
- 102100033246 Lysine-specific demethylase 5A Human genes 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 125000003342 alkenyl group Chemical group 0.000 description 9
- 125000000304 alkynyl group Chemical group 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 101100477411 Dictyostelium discoideum set1 gene Proteins 0.000 description 8
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- HWXBTNAVRSUOJR-UHFFFAOYSA-N alpha-hydroxyglutaric acid Natural products OC(=O)C(O)CCC(O)=O HWXBTNAVRSUOJR-UHFFFAOYSA-N 0.000 description 8
- 229940009533 alpha-ketoglutaric acid Drugs 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 229960002685 biotin Drugs 0.000 description 8
- 239000011616 biotin Substances 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000011987 methylation Effects 0.000 description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 7
- UGRMITBWUVWUEB-UHFFFAOYSA-N 1-$l^{1}-oxidanyl-3-methylbenzene Chemical group CC1=CC=CC([O])=C1 UGRMITBWUVWUEB-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 125000003107 substituted aryl group Chemical group 0.000 description 6
- 125000003831 tetrazolyl group Chemical group 0.000 description 6
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 5
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 5
- 239000007832 Na2SO4 Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 238000000423 cell based assay Methods 0.000 description 5
- 125000004093 cyano group Chemical group *C#N 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 125000001207 fluorophenyl group Chemical group 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 150000002430 hydrocarbons Chemical group 0.000 description 5
- 125000001841 imino group Chemical group [H]N=* 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 125000004430 oxygen atom Chemical group O* 0.000 description 5
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 4
- NGXQPTSMRJRJNM-UHFFFAOYSA-N 1H-pyrrolo[3,2-b]pyridine-7-carboxamide Chemical compound N1C=CC2=NC=CC(=C21)C(=O)N NGXQPTSMRJRJNM-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 4
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 108010077544 Chromatin Proteins 0.000 description 4
- 229940126062 Compound A Drugs 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000007995 HEPES buffer Substances 0.000 description 4
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000012131 assay buffer Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 229950004398 broxuridine Drugs 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 210000003483 chromatin Anatomy 0.000 description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 4
- 230000017858 demethylation Effects 0.000 description 4
- 238000010520 demethylation reaction Methods 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- IMBKASBLAKCLEM-UHFFFAOYSA-L ferrous ammonium sulfate (anhydrous) Chemical compound [NH4+].[NH4+].[Fe+2].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O IMBKASBLAKCLEM-UHFFFAOYSA-L 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- LTFTWJYRQNTCHI-UHFFFAOYSA-N hex-1-yn-3-ol Chemical compound CCCC(O)C#C LTFTWJYRQNTCHI-UHFFFAOYSA-N 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- KSZMBXHYSQDICN-UHFFFAOYSA-N methyl 3-amino-2-chloropyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(Cl)=C1N KSZMBXHYSQDICN-UHFFFAOYSA-N 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 125000004043 oxo group Chemical group O=* 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 4
- 235000019187 sodium-L-ascorbate Nutrition 0.000 description 4
- 239000011755 sodium-L-ascorbate Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 125000000464 thioxo group Chemical group S=* 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 125000003944 tolyl group Chemical group 0.000 description 4
- 241000701447 unidentified baculovirus Species 0.000 description 4
- NUHPPDIXDWJTCM-UHFFFAOYSA-N 2-(piperidine-1-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound OC(=O)c1ccnc2cc([nH]c12)C(=O)N1CCCCC1 NUHPPDIXDWJTCM-UHFFFAOYSA-N 0.000 description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 208000005623 Carcinogenesis Diseases 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000016624 JmjC domains Human genes 0.000 description 3
- 108050006228 JmjC domains Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- WRWYGOVGIGCDLE-UHFFFAOYSA-N [O]c1ccccc1F Chemical group [O]c1ccccc1F WRWYGOVGIGCDLE-UHFFFAOYSA-N 0.000 description 3
- 125000004419 alkynylene group Chemical group 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 150000005840 aryl radicals Chemical class 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000036952 cancer formation Effects 0.000 description 3
- 231100000504 carcinogenesis Toxicity 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Chemical group 0.000 description 3
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 125000005767 propoxymethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])[#8]C([H])([H])* 0.000 description 3
- 229940107700 pyruvic acid Drugs 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- WIGCCXQLCAMLDY-UHFFFAOYSA-N 1-cyclopropylbut-3-yn-2-ol Chemical compound C#CC(O)CC1CC1 WIGCCXQLCAMLDY-UHFFFAOYSA-N 0.000 description 2
- FTVOPYIWXFTNOS-UHFFFAOYSA-N 1-methoxy-4-prop-2-ynylbenzene Chemical compound COC1=CC=C(CC#C)C=C1 FTVOPYIWXFTNOS-UHFFFAOYSA-N 0.000 description 2
- PIXWYGUHIAUIFC-UHFFFAOYSA-N 1-pyrrolidin-1-ylpropane-1,2-dione Chemical compound CC(=O)C(=O)N1CCCC1 PIXWYGUHIAUIFC-UHFFFAOYSA-N 0.000 description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical group C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- LJSLTRVLEYBZQF-UHFFFAOYSA-N 2-(2,2-dimethylpyrrolidine-1-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound CC1(C)CCCN1C(=O)c1cc2nccc(C(O)=O)c2[nH]1 LJSLTRVLEYBZQF-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- FEZIKLVLFANZBD-UHFFFAOYSA-N 2-phenyl-1h-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound N1C=2C(C(=O)O)=CC=NC=2C=C1C1=CC=CC=C1 FEZIKLVLFANZBD-UHFFFAOYSA-N 0.000 description 2
- 125000004362 3,4,5-trichlorophenyl group Chemical group [H]C1=C(Cl)C(Cl)=C(Cl)C([H])=C1* 0.000 description 2
- UAFNSWUBMGTOQA-UHFFFAOYSA-N 3-chloro-1h-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound OC(=O)C1=CC=NC2=C1NC=C2Cl UAFNSWUBMGTOQA-UHFFFAOYSA-N 0.000 description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 2
- BZCOHGUBYSDFET-UHFFFAOYSA-N 4-chloro-3-methoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC=C1Cl BZCOHGUBYSDFET-UHFFFAOYSA-N 0.000 description 2
- DPBMIXCQVLWNGP-UHFFFAOYSA-N 5-prop-2-ynoxy-2,3-dihydro-1-benzofuran Chemical compound C#CCOc1ccc2OCCc2c1 DPBMIXCQVLWNGP-UHFFFAOYSA-N 0.000 description 2
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 108010034791 Heterochromatin Proteins 0.000 description 2
- 101710160287 Heterochromatin protein 1 Proteins 0.000 description 2
- 101001050886 Homo sapiens Lysine-specific histone demethylase 1A Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000058057 JmjC domain-containing Human genes 0.000 description 2
- 108700001203 JmjC domain-containing Proteins 0.000 description 2
- 102100024985 Lysine-specific histone demethylase 1A Human genes 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical group C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- 230000018199 S phase Effects 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 235000009697 arginine Nutrition 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 108010011222 cyclo(Arg-Pro) Proteins 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 210000001671 embryonic stem cell Anatomy 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000008029 eradication Effects 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 210000004458 heterochromatin Anatomy 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 description 2
- 125000002636 imidazolinyl group Chemical group 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical group C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 101150076630 jhdm-1 gene Proteins 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 125000003588 lysine group Chemical class [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- LROBJRRFCPYLIT-UHFFFAOYSA-M magnesium;ethyne;bromide Chemical compound [Mg+2].[Br-].[C-]#C LROBJRRFCPYLIT-UHFFFAOYSA-M 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- SDWNRFPXTLRTRY-UHFFFAOYSA-N methyl 2-(1-hydroxy-1-phenylethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc([nH]c12)C(C)(O)c1ccccc1 SDWNRFPXTLRTRY-UHFFFAOYSA-N 0.000 description 2
- AZPANMQXTFKPAS-UHFFFAOYSA-N methyl 2-(2,2-dimethylpyrrolidine-1-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc([nH]c12)C(=O)N1CCCC1(C)C AZPANMQXTFKPAS-UHFFFAOYSA-N 0.000 description 2
- KQTRKXVPRHGMMK-UHFFFAOYSA-N methyl 2-(2,3-dihydroindole-1-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc([nH]c12)C(=O)N1CCc2ccccc12 KQTRKXVPRHGMMK-UHFFFAOYSA-N 0.000 description 2
- KKKRNYIFNPXOHS-UHFFFAOYSA-N methyl 2-(2-cyanoethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc(CCC#N)[nH]c12 KKKRNYIFNPXOHS-UHFFFAOYSA-N 0.000 description 2
- GVLLSNIOJVKUQY-UHFFFAOYSA-N methyl 2-(2-phenylethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc(CCc3ccccc3)[nH]c12 GVLLSNIOJVKUQY-UHFFFAOYSA-N 0.000 description 2
- FJXLPPZIUHDDNM-UHFFFAOYSA-N methyl 2-(3,4-dihydro-2H-quinoline-1-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound N1(CCCC2=CC=CC=C12)C(=O)C1=CC2=NC=CC(=C2N1)C(=O)OC FJXLPPZIUHDDNM-UHFFFAOYSA-N 0.000 description 2
- LOTMOAVJJPAAHQ-UHFFFAOYSA-N methyl 2-(3-phenylpiperidine-1-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc([nH]c12)C(=O)N1CCCC(C1)c1ccccc1 LOTMOAVJJPAAHQ-UHFFFAOYSA-N 0.000 description 2
- UXZDAQNEYNJZBT-UHFFFAOYSA-N methyl 2-(3-phenylpyrrolidine-1-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc([nH]c12)C(=O)N1CCC(C1)c1ccccc1 UXZDAQNEYNJZBT-UHFFFAOYSA-N 0.000 description 2
- YROWUSARYSGPIU-UHFFFAOYSA-N methyl 2-(cyclohexylmethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc(CC3CCCCC3)[nH]c12 YROWUSARYSGPIU-UHFFFAOYSA-N 0.000 description 2
- BWUQYUDHNYIGTF-UHFFFAOYSA-N methyl 2-(cyclopentylmethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc(CC3CCCC3)[nH]c12 BWUQYUDHNYIGTF-UHFFFAOYSA-N 0.000 description 2
- LSCAEDVJQCRXLG-UHFFFAOYSA-N methyl 2-(hydroxymethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)C1=C2C(=NC=C1)C=C(N2)CO LSCAEDVJQCRXLG-UHFFFAOYSA-N 0.000 description 2
- DTQHKSVJUFHWRN-UHFFFAOYSA-N methyl 2-(methoxymethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COCc1cc2nccc(C(=O)OC)c2[nH]1 DTQHKSVJUFHWRN-UHFFFAOYSA-N 0.000 description 2
- JSXIVOWOFDZPPT-UHFFFAOYSA-N methyl 2-(piperidine-1-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc([nH]c12)C(=O)N1CCCCC1 JSXIVOWOFDZPPT-UHFFFAOYSA-N 0.000 description 2
- HZWMRJFJYABKOZ-UHFFFAOYSA-N methyl 2-[(4-fluorophenyl)methyl]-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc(Cc3ccc(F)cc3)[nH]c12 HZWMRJFJYABKOZ-UHFFFAOYSA-N 0.000 description 2
- FQEMSHRKUOJNBC-UHFFFAOYSA-N methyl 2-[hydroxy-(1-methylpyrazol-4-yl)methyl]-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc([nH]c12)C(O)c1cnn(C)c1 FQEMSHRKUOJNBC-UHFFFAOYSA-N 0.000 description 2
- RYPJKYGBDQKURZ-UHFFFAOYSA-N methyl 3-amino-2-(2-phenylethynyl)pyridine-4-carboxylate Chemical compound COC(=O)c1ccnc(C#Cc2ccccc2)c1N RYPJKYGBDQKURZ-UHFFFAOYSA-N 0.000 description 2
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000001323 posttranslational effect Effects 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 230000019639 protein methylation Effects 0.000 description 2
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000009758 senescence Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 229910052717 sulfur Chemical group 0.000 description 2
- 239000011593 sulfur Chemical group 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 125000004568 thiomorpholinyl group Chemical group 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
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- GKPOMITUDGXOSB-SCSAIBSYSA-N (2r)-but-3-yn-2-ol Chemical compound C[C@@H](O)C#C GKPOMITUDGXOSB-SCSAIBSYSA-N 0.000 description 1
- 125000006732 (C1-C15) alkyl group Chemical group 0.000 description 1
- 125000006313 (C5-C8) alkyl group Chemical group 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 101150084750 1 gene Proteins 0.000 description 1
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 1
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 1
- XUQVRZIIKILVTA-UHFFFAOYSA-N 1,3-dichloro-5-prop-2-ynoxybenzene Chemical compound ClC1=CC(Cl)=CC(OCC#C)=C1 XUQVRZIIKILVTA-UHFFFAOYSA-N 0.000 description 1
- ZOFTWFDLBJRYJI-UHFFFAOYSA-N 1,3-difluoro-5-prop-2-ynoxybenzene Chemical compound FC1=CC(F)=CC(OCC#C)=C1 ZOFTWFDLBJRYJI-UHFFFAOYSA-N 0.000 description 1
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 description 1
- YUTFQTAITWWGFH-UHFFFAOYSA-N 1-(1-benzofuran-2-yl)ethanone Chemical compound C1=CC=C2OC(C(=O)C)=CC2=C1 YUTFQTAITWWGFH-UHFFFAOYSA-N 0.000 description 1
- RNULYPCVVHDEFF-UHFFFAOYSA-N 1-(3-methoxyphenyl)prop-2-yn-1-ol Chemical compound COC1=CC=CC(C(O)C#C)=C1 RNULYPCVVHDEFF-UHFFFAOYSA-N 0.000 description 1
- GHTICGMHEPKNMD-UHFFFAOYSA-N 1-(3-methylphenyl)prop-2-yn-1-ol Chemical compound CC1=CC=CC(C(O)C#C)=C1 GHTICGMHEPKNMD-UHFFFAOYSA-N 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- VRKIQHITTICHHE-UHFFFAOYSA-N 1-chloro-2-(1-propoxyprop-2-ynyl)benzene Chemical compound CCCOC(C#C)c1ccccc1Cl VRKIQHITTICHHE-UHFFFAOYSA-N 0.000 description 1
- MWRDOGDGBQFLTG-UHFFFAOYSA-N 1-chloro-3-prop-2-ynoxybenzene Chemical compound ClC1=CC=CC(OCC#C)=C1 MWRDOGDGBQFLTG-UHFFFAOYSA-N 0.000 description 1
- USRMDNZIKVMDKH-UHFFFAOYSA-N 1-chloro-4-prop-2-ynoxybenzene Chemical compound ClC1=CC=C(OCC#C)C=C1 USRMDNZIKVMDKH-UHFFFAOYSA-N 0.000 description 1
- GNZUKUHRXXDNFS-UHFFFAOYSA-N 1-chloro-4-prop-2-ynylbenzene Chemical compound ClC1=CC=C(CC#C)C=C1 GNZUKUHRXXDNFS-UHFFFAOYSA-N 0.000 description 1
- NFQRIJRWUCDRPN-UHFFFAOYSA-N 1-cyclopropylprop-2-yn-1-ol Chemical compound C#CC(O)C1CC1 NFQRIJRWUCDRPN-UHFFFAOYSA-N 0.000 description 1
- MYBSUWNEMXUTAX-UHFFFAOYSA-N 1-ethynyl-2-methylbenzene Chemical compound CC1=CC=CC=C1C#C MYBSUWNEMXUTAX-UHFFFAOYSA-N 0.000 description 1
- QYLFHLNFIHBCPR-UHFFFAOYSA-N 1-ethynylcyclohexan-1-ol Chemical compound C#CC1(O)CCCCC1 QYLFHLNFIHBCPR-UHFFFAOYSA-N 0.000 description 1
- QPACLFFIDGQFRT-UHFFFAOYSA-N 1-ethynylcyclopropan-1-ol Chemical compound C#CC1(O)CC1 QPACLFFIDGQFRT-UHFFFAOYSA-N 0.000 description 1
- NYPHWSBGBCOPCM-UHFFFAOYSA-N 1-fluoro-2-prop-2-ynoxybenzene Chemical compound FC1=CC=CC=C1OCC#C NYPHWSBGBCOPCM-UHFFFAOYSA-N 0.000 description 1
- FXGXMJFFQWBIQY-UHFFFAOYSA-N 1-fluoro-3-prop-2-ynoxybenzene Chemical compound FC1=CC=CC(OCC#C)=C1 FXGXMJFFQWBIQY-UHFFFAOYSA-N 0.000 description 1
- KVRJLSPSYFYNAA-UHFFFAOYSA-N 1-fluoro-4-prop-2-ynoxybenzene Chemical compound FC1=CC=C(OCC#C)C=C1 KVRJLSPSYFYNAA-UHFFFAOYSA-N 0.000 description 1
- YRHCGFRCOATEFD-UHFFFAOYSA-N 1-methoxy-4-prop-2-ynoxybenzene Chemical compound COC1=CC=C(OCC#C)C=C1 YRHCGFRCOATEFD-UHFFFAOYSA-N 0.000 description 1
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 1
- 125000005987 1-oxo-thiomorpholinyl group Chemical group 0.000 description 1
- IBXNCJKFFQIKKY-UHFFFAOYSA-N 1-pentyne Chemical compound CCCC#C IBXNCJKFFQIKKY-UHFFFAOYSA-N 0.000 description 1
- BRORDTRRXFYCDZ-UHFFFAOYSA-N 1-prop-2-ynoxy-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(OCC#C)C=C1 BRORDTRRXFYCDZ-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- XWIYUCRMWCHYJR-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical group C1=CC=C2NC=CC2=N1 XWIYUCRMWCHYJR-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- PHODFIDDEBEGCS-UHFFFAOYSA-N 2,2-dimethylpyrrolidine Chemical compound CC1(C)CCCN1 PHODFIDDEBEGCS-UHFFFAOYSA-N 0.000 description 1
- JNYKOGUXPNAUIB-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-5-ol Chemical compound OC1=CC=C2OCCC2=C1 JNYKOGUXPNAUIB-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical class OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- HNNQVNLVWCLBCR-UHFFFAOYSA-N 2,4-dichloro-1-prop-2-ynylbenzene Chemical compound ClC1=CC=C(CC#C)C(Cl)=C1 HNNQVNLVWCLBCR-UHFFFAOYSA-N 0.000 description 1
- UYKGPJOTPPQTPS-UHFFFAOYSA-N 2-(1-hydroxy-1-phenylethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound OC(C)(C1=CC=CC=C1)C1=CC2=NC=CC(=C2N1)C(=O)O UYKGPJOTPPQTPS-UHFFFAOYSA-N 0.000 description 1
- MDKIIFAUVUDOPJ-UHFFFAOYSA-N 2-(1-hydroxycyclohexyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound OC(=O)c1ccnc2cc([nH]c12)C1(O)CCCCC1 MDKIIFAUVUDOPJ-UHFFFAOYSA-N 0.000 description 1
- RMCMBFPHTFWEBT-UHFFFAOYSA-N 2-(1-hydroxyethyl)-1h-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound C1=CC(C(O)=O)=C2NC(C(O)C)=CC2=N1 RMCMBFPHTFWEBT-UHFFFAOYSA-N 0.000 description 1
- VFNSKTHFPJWUKV-UHFFFAOYSA-N 2-(1-phenoxyethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound CC(Oc1ccccc1)c1cc2nccc(C(O)=O)c2[nH]1 VFNSKTHFPJWUKV-UHFFFAOYSA-N 0.000 description 1
- KUACYTWQTKCWOZ-UHFFFAOYSA-N 2-(2,3-dihydro-1-benzofuran-5-yloxymethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound OC(=O)c1ccnc2cc(COc3ccc4OCCc4c3)[nH]c12 KUACYTWQTKCWOZ-UHFFFAOYSA-N 0.000 description 1
- HYYJZVSCEWUATR-UHFFFAOYSA-N 2-(2,3-dihydroindole-1-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound OC(=O)c1ccnc2cc([nH]c12)C(=O)N1CCc2ccccc12 HYYJZVSCEWUATR-UHFFFAOYSA-N 0.000 description 1
- QGWDKDJPSMMAIM-UHFFFAOYSA-N 2-(2-cyanoethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound OC(=O)c1ccnc2cc(CCC#N)[nH]c12 QGWDKDJPSMMAIM-UHFFFAOYSA-N 0.000 description 1
- FODSHMOMERZNFO-UHFFFAOYSA-N 2-(2-phenylethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound C1(=CC=CC=C1)CCC1=CC2=NC=CC(=C2N1)C(=O)O FODSHMOMERZNFO-UHFFFAOYSA-N 0.000 description 1
- XPBKVYOBTSXQJV-UHFFFAOYSA-N 2-(3,4-dihydro-2H-quinoline-1-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound N1(CCCC2=CC=CC=C12)C(=O)C1=CC2=NC=CC(=C2N1)C(=O)O XPBKVYOBTSXQJV-UHFFFAOYSA-N 0.000 description 1
- XYHXZRBZNBOLAJ-UHFFFAOYSA-N 2-(3-phenylpiperidine-1-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound C1(=CC=CC=C1)C1CN(CCC1)C(=O)C1=CC2=NC=CC(=C2N1)C(=O)O XYHXZRBZNBOLAJ-UHFFFAOYSA-N 0.000 description 1
- ATFLOGYNEKTCMN-UHFFFAOYSA-N 2-(3-phenylpyrrolidine-1-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound OC(=O)c1ccnc2cc([nH]c12)C(=O)N1CCC(C1)c1ccccc1 ATFLOGYNEKTCMN-UHFFFAOYSA-N 0.000 description 1
- YYVQUZIWKZVUOA-UHFFFAOYSA-N 2-(4,4-dimethylpiperidine-1-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound CC1(CCN(CC1)C(=O)C1=CC2=NC=CC(=C2N1)C(=O)O)C YYVQUZIWKZVUOA-UHFFFAOYSA-N 0.000 description 1
- LPFWATLXDCIHNH-UHFFFAOYSA-N 2-(cyclohexylmethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound OC(=O)c1ccnc2cc(CC3CCCCC3)[nH]c12 LPFWATLXDCIHNH-UHFFFAOYSA-N 0.000 description 1
- OZJOKUHQQZYMME-UHFFFAOYSA-N 2-(cyclopentylmethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound OC(=O)c1ccnc2cc(CC3CCCC3)[nH]c12 OZJOKUHQQZYMME-UHFFFAOYSA-N 0.000 description 1
- QGEQDCNJTLKLCD-UHFFFAOYSA-N 2-(hydroxymethyl)-1h-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound C1=CC(C(O)=O)=C2NC(CO)=CC2=N1 QGEQDCNJTLKLCD-UHFFFAOYSA-N 0.000 description 1
- QBJBXNHYPDLIAQ-UHFFFAOYSA-N 2-(methoxymethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound COCc1cc2nccc(C(O)=O)c2[nH]1 QBJBXNHYPDLIAQ-UHFFFAOYSA-N 0.000 description 1
- FFZURRPWJDSXFU-UHFFFAOYSA-N 2-(phenoxymethyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound OC(=O)c1ccnc2cc(COc3ccccc3)[nH]c12 FFZURRPWJDSXFU-UHFFFAOYSA-N 0.000 description 1
- CEIHDMRTHCSEQL-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound OC(=O)c1ccnc2cc(Cc3ccc(F)cc3)[nH]c12 CEIHDMRTHCSEQL-UHFFFAOYSA-N 0.000 description 1
- SZPUXNJWZYAGNU-UHFFFAOYSA-N 2-[hydroxy-(1-methylpyrazol-4-yl)methyl]-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid Chemical compound Cn1cc(cn1)C(O)c1cc2nccc(C(O)=O)c2[nH]1 SZPUXNJWZYAGNU-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical class OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 description 1
- TUHIBIVYQLRGME-UHFFFAOYSA-N 2-cyclopropylacetaldehyde Chemical compound O=CCC1CC1 TUHIBIVYQLRGME-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
- 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
- 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- BTJOKRSEWSGLSI-UHFFFAOYSA-N 3,4-dichloro-5-fluorobenzaldehyde Chemical compound FC1=CC(C=O)=CC(Cl)=C1Cl BTJOKRSEWSGLSI-UHFFFAOYSA-N 0.000 description 1
- ZWUSBSHBFFPRNE-UHFFFAOYSA-N 3,4-dichlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1Cl ZWUSBSHBFFPRNE-UHFFFAOYSA-N 0.000 description 1
- JPHKMYXKNKLNDF-UHFFFAOYSA-N 3,4-difluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1F JPHKMYXKNKLNDF-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- GVORVQPNNSASDM-UHFFFAOYSA-N 3-chloro-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1Cl GVORVQPNNSASDM-UHFFFAOYSA-N 0.000 description 1
- YACFFSVYSPMSGS-UHFFFAOYSA-N 3-methoxyprop-1-yne Chemical compound COCC#C YACFFSVYSPMSGS-UHFFFAOYSA-N 0.000 description 1
- NZYBILDYPCVNMU-UHFFFAOYSA-N 3-phenylpiperidine Chemical compound C1CCNCC1C1=CC=CC=C1 NZYBILDYPCVNMU-UHFFFAOYSA-N 0.000 description 1
- PRRFFTYUBPGHLE-UHFFFAOYSA-N 3-phenylpyrrolidine Chemical compound C1NCCC1C1=CC=CC=C1 PRRFFTYUBPGHLE-UHFFFAOYSA-N 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- IECMOFZIMWVOAS-UHFFFAOYSA-N 4,4-dimethylpiperidine Chemical compound CC1(C)CCNCC1 IECMOFZIMWVOAS-UHFFFAOYSA-N 0.000 description 1
- BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 1
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- BDXWZLJYTJSTDF-UHFFFAOYSA-N 4-chloro-3-(2,2,2-trifluoroethoxy)benzaldehyde Chemical compound FC(COC=1C=C(C=O)C=CC1Cl)(F)F BDXWZLJYTJSTDF-UHFFFAOYSA-N 0.000 description 1
- XOHOCMBXDFQWDF-UHFFFAOYSA-N 4-chloro-3-(trifluoromethoxy)benzaldehyde Chemical compound FC(F)(F)OC1=CC(C=O)=CC=C1Cl XOHOCMBXDFQWDF-UHFFFAOYSA-N 0.000 description 1
- AZMDWRPTDCIFRD-UHFFFAOYSA-N 4-chloro-3-fluorobenzaldehyde Chemical compound FC1=CC(C=O)=CC=C1Cl AZMDWRPTDCIFRD-UHFFFAOYSA-N 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
- UTIFIONYBLSHIL-UHFFFAOYSA-N 4-methylpent-1-yn-3-ol Chemical compound CC(C)C(O)C#C UTIFIONYBLSHIL-UHFFFAOYSA-N 0.000 description 1
- 125000005986 4-piperidonyl group Chemical group 0.000 description 1
- FBTKJZVYFGLMEA-UHFFFAOYSA-N 4-prop-2-ynylbenzonitrile Chemical compound C#CCC1=CC=C(C#N)C=C1 FBTKJZVYFGLMEA-UHFFFAOYSA-N 0.000 description 1
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 1
- KAWTWTAGDVIOTE-UHFFFAOYSA-N 5-chloro-5-prop-2-ynoxycyclohexa-1,3-diene Chemical compound ClC1(CC=CC=C1)OCC#C KAWTWTAGDVIOTE-UHFFFAOYSA-N 0.000 description 1
- XJZOJWSYXLSYPW-UHFFFAOYSA-N 5-fluoro-5-prop-2-ynoxycyclohexa-1,3-diene Chemical compound FC1(CC=CC=C1)OCC#C XJZOJWSYXLSYPW-UHFFFAOYSA-N 0.000 description 1
- BWIOURVJVDKDOC-UHFFFAOYSA-N 6-bromo-1-(chloromethyl)-2-methoxynaphthalene Chemical compound C1=C(Br)C=CC2=C(CCl)C(OC)=CC=C21 BWIOURVJVDKDOC-UHFFFAOYSA-N 0.000 description 1
- XTSRCXUVYOTHKP-UHFFFAOYSA-N 6-chloro-2-fluoro-6-prop-2-ynoxycyclohexa-1,3-diene Chemical compound ClC1(CC=CC(=C1)F)OCC#C XTSRCXUVYOTHKP-UHFFFAOYSA-N 0.000 description 1
- KYARBIJYVGJZLB-UHFFFAOYSA-N 7-amino-4-hydroxy-2-naphthalenesulfonic acid Chemical compound OC1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 KYARBIJYVGJZLB-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108700020463 BRCA1 Proteins 0.000 description 1
- 102000036365 BRCA1 Human genes 0.000 description 1
- 101150072950 BRCA1 gene Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVRZVBIAOQNIKQ-UHFFFAOYSA-N C1(CC1)COC=1C=C(C=O)C=CC1Cl Chemical compound C1(CC1)COC=1C=C(C=O)C=CC1Cl BVRZVBIAOQNIKQ-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 102100035888 Caveolin-1 Human genes 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 101100130497 Drosophila melanogaster Mical gene Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 102100039869 Histone H2B type F-S Human genes 0.000 description 1
- 108010036115 Histone Methyltransferases Proteins 0.000 description 1
- 102000011787 Histone Methyltransferases Human genes 0.000 description 1
- 102100035864 Histone lysine demethylase PHF8 Human genes 0.000 description 1
- 101000715467 Homo sapiens Caveolin-1 Proteins 0.000 description 1
- 101001035372 Homo sapiens Histone H2B type F-S Proteins 0.000 description 1
- 101001000378 Homo sapiens Histone lysine demethylase PHF8 Proteins 0.000 description 1
- 101000613958 Homo sapiens Lysine-specific demethylase 2A Proteins 0.000 description 1
- 101000613629 Homo sapiens Lysine-specific demethylase 4B Proteins 0.000 description 1
- 101001088895 Homo sapiens Lysine-specific demethylase 4D Proteins 0.000 description 1
- 101001088900 Homo sapiens Lysine-specific demethylase 4E Proteins 0.000 description 1
- 101001088887 Homo sapiens Lysine-specific demethylase 5C Proteins 0.000 description 1
- 101001088879 Homo sapiens Lysine-specific demethylase 5D Proteins 0.000 description 1
- 101000692954 Homo sapiens Lysine-specific demethylase PHF2 Proteins 0.000 description 1
- 101001056567 Homo sapiens Protein Jumonji Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 101150086476 KDM5B gene Proteins 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 102100040598 Lysine-specific demethylase 2A Human genes 0.000 description 1
- 102100040860 Lysine-specific demethylase 4B Human genes 0.000 description 1
- 102100033231 Lysine-specific demethylase 4D Human genes 0.000 description 1
- 102100033232 Lysine-specific demethylase 4E Human genes 0.000 description 1
- 102100033249 Lysine-specific demethylase 5C Human genes 0.000 description 1
- 102100033143 Lysine-specific demethylase 5D Human genes 0.000 description 1
- 102100026395 Lysine-specific demethylase PHF2 Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 101710143112 Mothers against decapentaplegic homolog 4 Proteins 0.000 description 1
- 206010073150 Multiple endocrine neoplasia Type 1 Diseases 0.000 description 1
- 101100345589 Mus musculus Mical1 gene Proteins 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
- 108010047956 Nucleosomes Proteins 0.000 description 1
- 102100027069 Odontogenic ameloblast-associated protein Human genes 0.000 description 1
- 101710091533 Odontogenic ameloblast-associated protein Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 1
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
- 229910021120 PdC12 Inorganic materials 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 244000025272 Persea americana Species 0.000 description 1
- 235000008673 Persea americana Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100025733 Protein Jumonji 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
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 108700025701 Retinoblastoma Genes Proteins 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
- 102000049937 Smad4 Human genes 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- RMCZMJARTQKQHR-UHFFFAOYSA-N [cyclopropyl(hydroxy)methyl] 1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound C1(CC1)C(O)OC(=O)C1=C2C(=NC=C1)C=CN2 RMCZMJARTQKQHR-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 230000011759 adipose tissue development Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010719 annulation reaction Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 150000001484 arginines Chemical class 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000005870 benzindolyl group Chemical group 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000005875 benzo[b][1,4]dioxepinyl group Chemical group 0.000 description 1
- 125000005876 benzo[b][1,4]oxazinyl group Chemical group 0.000 description 1
- 125000005873 benzo[d]thiazolyl group Chemical group 0.000 description 1
- 125000000928 benzodioxinyl group Chemical group O1C(=COC2=C1C=CC=C2)* 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000005878 benzonaphthofuranyl group Chemical group 0.000 description 1
- 125000005872 benzooxazolyl group Chemical group 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 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
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- SQTYUDHPJGXEFH-UHFFFAOYSA-N but-3-yn-2-yloxybenzene Chemical compound C#CC(C)OC1=CC=CC=C1 SQTYUDHPJGXEFH-UHFFFAOYSA-N 0.000 description 1
- LMJIECGJNREYCB-UHFFFAOYSA-N but-3-ynoxybenzene Chemical compound C#CCCOC1=CC=CC=C1 LMJIECGJNREYCB-UHFFFAOYSA-N 0.000 description 1
- QDEOKXOYHYUKMS-UHFFFAOYSA-N but-3-ynylbenzene Chemical compound C#CCCC1=CC=CC=C1 QDEOKXOYHYUKMS-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- ILAJWURWJKXJPW-UHFFFAOYSA-N butanedioic acid;octanedioic acid Chemical class OC(=O)CCC(O)=O.OC(=O)CCCCCCC(O)=O ILAJWURWJKXJPW-UHFFFAOYSA-N 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000003426 co-catalyst Substances 0.000 description 1
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 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 1
- 238000007366 cycloisomerization reaction Methods 0.000 description 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 125000005507 decahydroisoquinolyl group Chemical group 0.000 description 1
- 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 125000005509 dibenzothiophenyl group Chemical group 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 125000004188 dichlorophenyl group Chemical group 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 230000019975 dosage compensation by inactivation of X chromosome Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- TXVJSWLZYQMWPC-UHFFFAOYSA-N ethynylcyclopentane Chemical compound C#CC1CCCC1 TXVJSWLZYQMWPC-UHFFFAOYSA-N 0.000 description 1
- NPTDXPDGUHAFKC-UHFFFAOYSA-N ethynylcyclopropane Chemical group C#CC1CC1 NPTDXPDGUHAFKC-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical group C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000003844 furanonyl group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 125000000262 haloalkenyl group Chemical group 0.000 description 1
- 125000000232 haloalkynyl group Chemical group 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 125000005114 heteroarylalkoxy group Chemical group 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- 235000014304 histidine Nutrition 0.000 description 1
- 102000033785 histone binding proteins Human genes 0.000 description 1
- 108091009732 histone binding proteins Proteins 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 1
- 201000010985 invasive ductal carcinoma Diseases 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical class CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 150000004701 malic acid derivatives Chemical class 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- VTOAKTBHCSDFGQ-UHFFFAOYSA-N methyl 2-(1-hydroxycyclohexyl)-1h-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound N1C=2C(C(=O)OC)=CC=NC=2C=C1C1(O)CCCCC1 VTOAKTBHCSDFGQ-UHFFFAOYSA-N 0.000 description 1
- UGCQDKIVJKTGIJ-UHFFFAOYSA-N methyl 2-(1-hydroxyethyl)-1h-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)C1=CC=NC2=C1NC(C(C)O)=C2 UGCQDKIVJKTGIJ-UHFFFAOYSA-N 0.000 description 1
- GYXUXZPDFZYXBV-UHFFFAOYSA-N methyl 2-(3,4-dihydro-1H-isoquinoline-2-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc([nH]c12)C(=O)N1CCc2ccccc2C1 GYXUXZPDFZYXBV-UHFFFAOYSA-N 0.000 description 1
- DXODFNCCDMPWIP-UHFFFAOYSA-N methyl 2-(4,4-dimethylpiperidine-1-carbonyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc([nH]c12)C(=O)N1CCC(C)(C)CC1 DXODFNCCDMPWIP-UHFFFAOYSA-N 0.000 description 1
- CAZSDITUVPNQBH-UHFFFAOYSA-N methyl 2-[hydroxy-(2-methylpyrazol-3-yl)methyl]-1H-pyrrolo[3,2-b]pyridine-7-carboxylate Chemical compound COC(=O)c1ccnc2cc([nH]c12)C(O)c1ccnn1C CAZSDITUVPNQBH-UHFFFAOYSA-N 0.000 description 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical class COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000005322 morpholin-1-yl group Chemical group 0.000 description 1
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
- NOUUUQMKVOUUNR-UHFFFAOYSA-N n,n'-diphenylethane-1,2-diamine Chemical compound C=1C=CC=CC=1NCCNC1=CC=CC=C1 NOUUUQMKVOUUNR-UHFFFAOYSA-N 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000003518 norbornenyl group Chemical group C12(C=CC(CC1)C2)* 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 108020004017 nuclear receptors Proteins 0.000 description 1
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Chemical group C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
- 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
- 125000005061 octahydroisoindolyl group Chemical group C1(NCC2CCCCC12)* 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical class CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 230000006548 oncogenic transformation Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 238000005895 oxidative decarboxylation reaction Methods 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- LBSKEFWQPNVWTP-UHFFFAOYSA-N pent-1-yn-3-ol Chemical compound CCC(O)C#C LBSKEFWQPNVWTP-UHFFFAOYSA-N 0.000 description 1
- VMUWIDHKAIGONP-UHFFFAOYSA-N pent-4-ynenitrile Chemical compound C#CCCC#N VMUWIDHKAIGONP-UHFFFAOYSA-N 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000005498 phthalate group Chemical class 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960005141 piperazine Drugs 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- NGKSKVYWPINGLI-UHFFFAOYSA-N prop-2-ynylbenzene Chemical compound C#CCC1=CC=CC=C1 NGKSKVYWPINGLI-UHFFFAOYSA-N 0.000 description 1
- UARFKZSJGDQRLF-UHFFFAOYSA-N prop-2-ynylcyclohexane Chemical compound C#CCC1CCCCC1 UARFKZSJGDQRLF-UHFFFAOYSA-N 0.000 description 1
- VBTCAHMANZTRMG-UHFFFAOYSA-N prop-2-ynylcyclopentane Chemical compound C#CCC1CCCC1 VBTCAHMANZTRMG-UHFFFAOYSA-N 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000005985 thienyl[1,3]dithianyl group Chemical group 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 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
- 238000012546 transfer Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361778193P | 2013-03-12 | 2013-03-12 | |
| US61/778,193 | 2013-03-12 | ||
| PCT/US2014/023273 WO2014164708A1 (en) | 2013-03-12 | 2014-03-11 | Histone dementhylase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2903473A1 true CA2903473A1 (en) | 2014-10-09 |
Family
ID=51658949
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2903473A Abandoned CA2903473A1 (en) | 2013-03-12 | 2014-03-11 | Histone demethylase inhibitors |
Country Status (6)
| Country | Link |
|---|---|
| US (4) | US9738637B2 (oth) |
| EP (1) | EP2968282B1 (oth) |
| JP (1) | JP6320506B2 (oth) |
| AU (1) | AU2014249050B2 (oth) |
| CA (1) | CA2903473A1 (oth) |
| WO (1) | WO2014164708A1 (oth) |
Families Citing this family (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6320506B2 (ja) | 2013-03-12 | 2018-05-09 | セルジーン クオンティセル リサーチ，インク． | ヒストンデメチラーゼ阻害剤 |
| US10030017B2 (en) | 2014-09-17 | 2018-07-24 | Celgene Quanticel Research, Inc. | Histone demethylase inhibitors |
| MX2017003463A (es) | 2014-09-17 | 2017-07-13 | Celgene Quanticel Res Inc | Inhibidores de histona desmetilasa. |
| US9643965B2 (en) | 2014-09-17 | 2017-05-09 | Celgene Quantical Research, Inc. | Histone demethylase inhibitors |
| EP3204379B1 (en) * | 2014-10-10 | 2019-03-06 | Genentech, Inc. | Pyrrolidine amide compounds as histone demethylase inhibitors |
| NZ730475A (en) | 2014-10-29 | 2018-09-28 | Dong A St Co Ltd | Novel pyridopyrimidinone compounds for modulating the catalytic activity of histone lysine demethylases (kdms) |
| JP6970681B2 (ja) * | 2016-03-15 | 2021-11-24 | セルジーン クオンティセル リサーチ，インク． | ヒストンデメチラーゼ阻害剤 |
| US10150754B2 (en) | 2016-04-19 | 2018-12-11 | Celgene Quanticel Research, Inc. | Histone demethylase inhibitors |
| CN109414508A (zh) | 2016-05-27 | 2019-03-01 | 吉利德科学公司 | 使用ns5a、ns5b或ns3抑制剂治疗乙型肝炎病毒感染的方法 |
| BR102017010009A2 (pt) | 2016-05-27 | 2017-12-12 | Gilead Sciences, Inc. | Compounds for the treatment of hepatitis b virus infection |
| US20190256509A1 (en) * | 2016-06-08 | 2019-08-22 | Chrysalis, Inc. | Histone demethylase inhibitors |
| JOP20190024A1 (ar) | 2016-08-26 | 2019-02-19 | Gilead Sciences Inc | مركبات بيروليزين بها استبدال واستخداماتها |
| CN109923106B (zh) | 2016-09-02 | 2022-09-13 | 吉利德科学公司 | toll样受体调节剂化合物 |
| EP3507288B1 (en) | 2016-09-02 | 2020-08-26 | Gilead Sciences, Inc. | 4,6-diamino-pyrido[3,2-d]pyrimidine derivaties as toll like receptor modulators |
| IL265921B2 (en) | 2016-10-14 | 2024-05-01 | Prec Biosciences Inc | Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome |
| TWI820984B (zh) | 2017-01-31 | 2023-11-01 | 美商基利科學股份有限公司 | 替諾福韋埃拉酚胺(tenofovir alafenamide)之晶型 |
| UY37581A (es) | 2017-02-02 | 2018-08-31 | Gilead Sciences Inc | Compuestos para el tratamiento de la infección por virus de la hepatitis b |
| WO2018160356A1 (en) | 2017-02-28 | 2018-09-07 | University Of Massachusetts | Genetic and pharmacological transcriptional upregulation of the repressed fxn gene as a therapeutic strategy for friedreich ataxia |
| BR102018007822A2 (pt) | 2017-04-20 | 2018-11-06 | Gilead Sciences, Inc. | composto, métodos para inibir pd-1, pd-l1 e/ou interação de pd-1/pd-l1 e para tratamento de câncer, composição farmacêutica, e, kit para tratamento de ou prevenção de câncer ou uma doença ou condição |
| US10966999B2 (en) | 2017-12-20 | 2021-04-06 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3′3′ cyclic dinucleotides with phosphonate bond activating the sting adaptor protein |
| CN111511754B (zh) | 2017-12-20 | 2023-09-12 | 捷克共和国有机化学与生物化学研究所 | 活化sting转接蛋白的具有膦酸酯键的2’3’环状二核苷酸 |
| TWI707849B (zh) | 2018-02-13 | 2020-10-21 | 美商基利科學股份有限公司 | Pd‐1/pd‐l1抑制劑 |
| PL3759109T3 (pl) | 2018-02-26 | 2024-03-04 | Gilead Sciences, Inc. | Podstawione związki pirolizyny jako inhibitory replikacji hbv |
| WO2019195181A1 (en) | 2018-04-05 | 2019-10-10 | Gilead Sciences, Inc. | Antibodies and fragments thereof that bind hepatitis b virus protein x |
| TWI818007B (zh) | 2018-04-06 | 2023-10-11 | 捷克科學院有機化學與生物化學研究所 | 2'3'-環二核苷酸 |
| TWI833744B (zh) | 2018-04-06 | 2024-03-01 | 捷克科學院有機化學與生物化學研究所 | 3'3'-環二核苷酸 |
| TW202005654A (zh) | 2018-04-06 | 2020-02-01 | 捷克科學院有機化學與生物化學研究所 | ２，２，─環二核苷酸 |
| TW201945388A (zh) | 2018-04-12 | 2019-12-01 | 美商精密生物科學公司 | 對b型肝炎病毒基因體中之識別序列具有特異性之最佳化之經工程化巨核酸酶 |
| KR102591947B1 (ko) | 2018-04-19 | 2023-10-25 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| WO2019211799A1 (en) | 2018-05-03 | 2019-11-07 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2'3'-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide |
| EP3820572B1 (en) | 2018-07-13 | 2023-08-16 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| WO2020028097A1 (en) | 2018-08-01 | 2020-02-06 | Gilead Sciences, Inc. | Solid forms of (r)-11-(methoxymethyl)-12-(3-methoxypropoxy)-3,3-dimethyl-8-0x0-2,3,8,13b-tetrahydro-1h-pyrido[2,1-a]pyrrolo[1,2-c] phthalazine-7-c arboxylic acid |
| US11236085B2 (en) | 2018-10-24 | 2022-02-01 | Gilead Sciences, Inc. | PD-1/PD-L1 inhibitors |
| TW202136261A (zh) | 2018-10-31 | 2021-10-01 | 美商基利科學股份有限公司 | 經取代之6-氮雜苯并咪唑化合物 |
| TWI721623B (zh) | 2018-10-31 | 2021-03-11 | 美商基利科學股份有限公司 | 經取代之6-氮雜苯并咪唑化合物 |
| US11766447B2 (en) | 2019-03-07 | 2023-09-26 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3′3′-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide as sting modulator |
| KR102707808B1 (ko) | 2019-03-07 | 2024-09-19 | 인스티튜트 오브 오가닉 케미스트리 앤드 바이오케미스트리 에이에스 씨알 브이.브이.아이. | 2'3'-사이클릭 다이뉴클레오티드 및 이의 프로드럭 |
| EP3935066A1 (en) | 2019-03-07 | 2022-01-12 | Institute of Organic Chemistry and Biochemistry ASCR, V.V.I. | 3'3'-cyclic dinucleotides and prodrugs thereof |
| TW202210480A (zh) | 2019-04-17 | 2022-03-16 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TW202212339A (zh) | 2019-04-17 | 2022-04-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| US11453681B2 (en) | 2019-05-23 | 2022-09-27 | Gilead Sciences, Inc. | Substituted eneoxindoles and uses thereof |
| CR20210687A (es) | 2019-06-25 | 2022-03-03 | Gilead Sciences Inc | PROTEÍNAS DE FUSIÓN FLT3L-Fc Y MÉTODOS DE USO |
| WO2021011891A1 (en) | 2019-07-18 | 2021-01-21 | Gilead Sciences, Inc. | Long-acting formulations of tenofovir alafenamide |
| WO2021034804A1 (en) | 2019-08-19 | 2021-02-25 | Gilead Sciences, Inc. | Pharmaceutical formulations of tenofovir alafenamide |
| CN119770638A (zh) | 2019-09-30 | 2025-04-08 | 吉利德科学公司 | Hbv疫苗和治疗hbv的方法 |
| US12410418B2 (en) | 2019-12-06 | 2025-09-09 | Precision Biosciences, Inc. | Optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome |
| US11718637B2 (en) | 2020-03-20 | 2023-08-08 | Gilead Sciences, Inc. | Prodrugs of 4′-C-substituted-2-halo-2′- deoxyadenosine nucleosides and methods of making and using the same |
| PE20230779A1 (es) | 2020-08-07 | 2023-05-09 | Gilead Sciences Inc | Profarmacos de analogos de nucleotidos de fosfonamida y su uso farmaceutico |
| TWI815194B (zh) | 2020-10-22 | 2023-09-11 | 美商基利科學股份有限公司 | 介白素2-Fc融合蛋白及使用方法 |
| EP4337223A1 (en) | 2021-05-13 | 2024-03-20 | Gilead Sciences, Inc. | Combination of a tlr8 modulating compound and anti-hbv sirna therapeutics |
| KR20240005901A (ko) | 2021-06-23 | 2024-01-12 | 길리애드 사이언시즈, 인코포레이티드 | 디아실글리세롤 키나제 조절 화합물 |
| WO2022271677A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| WO2022271659A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| CA3222277A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| WO2025240246A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
| US20250345389A1 (en) | 2024-05-13 | 2025-11-13 | Gilead Sciences, Inc. | Combination therapies |
| WO2025240242A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
| WO2025240244A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies comprising bulevirtide and lonafarnib for use in the treatment of hepatitis d virus infection |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6232320B1 (en) * | 1998-06-04 | 2001-05-15 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| JP2004509059A (ja) * | 1999-06-03 | 2004-03-25 | アボット・ラボラトリーズ | 細胞接着抑制性抗炎症化合物 |
| DE10152306A1 (de) * | 2001-10-26 | 2003-07-24 | Asta Medica Ag | 2-Acylindolderivate mit neuen therapeutisch wertvollen Eigenschaften |
| PE20050206A1 (es) | 2003-05-26 | 2005-03-26 | Schering Ag | Composicion farmaceutica que contiene un inhibidor de histona deacetilasa |
| US7666898B2 (en) | 2005-11-03 | 2010-02-23 | Ilypsa, Inc. | Multivalent indole compounds and use thereof as phospholipase-A2 inhibitors |
| US7371862B2 (en) * | 2005-11-11 | 2008-05-13 | Pfizer Italia S.R.L. | Azaindolylidene derivatives as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them |
| MY148893A (en) * | 2006-12-04 | 2013-06-14 | Novartis Ag | Combination of an hdac inhibitor and an antimetabolite |
| US20100137398A1 (en) * | 2007-05-04 | 2010-06-03 | Novartis Ag | Use of hdac inhibitors for the treatment of gastrointestinal cancers |
| MX2010011168A (es) * | 2008-04-15 | 2010-12-21 | Pharmacyclics Inc | Inhibidores selectivos de histona-desacetilasa. |
| DE102008052943A1 (de) * | 2008-10-23 | 2010-04-29 | Merck Patent Gmbh | Azaindolderivate |
| JP2012107001A (ja) * | 2010-10-22 | 2012-06-07 | Shionogi & Co Ltd | インドールアミド化合物を含有する医薬 |
| JP6122006B2 (ja) * | 2011-08-15 | 2017-04-26 | ザ ユニバーシティ オブ ユタ リサーチ ファウンデイション | ヒストン脱メチル化酵素阻害剤としての、置換された（ｅ）−ｎ’−（１−フェニルエチリデン）ベンゾヒドラジド類似体 |
| WO2013028999A1 (en) | 2011-08-24 | 2013-02-28 | The Trustees Of Columbia University In The City Of New York | Small molecule inducers of gdnf as potential new therapeutics for neuropsychiatric disorders |
| WO2013143597A1 (en) * | 2012-03-29 | 2013-10-03 | Glaxo Group Limited | Demethylase enzymes inhibitors |
| US8969343B2 (en) | 2012-12-19 | 2015-03-03 | Quanticel Pharmaceuticals, Inc. | Histone demethylase inhibitors |
| JP6320506B2 (ja) | 2013-03-12 | 2018-05-09 | セルジーン クオンティセル リサーチ，インク． | ヒストンデメチラーゼ阻害剤 |
| MX2017003463A (es) | 2014-09-17 | 2017-07-13 | Celgene Quanticel Res Inc | Inhibidores de histona desmetilasa. |
-
2014
- 2014-03-11 JP JP2016501190A patent/JP6320506B2/ja not_active Expired - Fee Related
- 2014-03-11 EP EP14778281.7A patent/EP2968282B1/en not_active Not-in-force
- 2014-03-11 WO PCT/US2014/023273 patent/WO2014164708A1/en not_active Ceased
- 2014-03-11 CA CA2903473A patent/CA2903473A1/en not_active Abandoned
- 2014-03-11 US US14/774,329 patent/US9738637B2/en active Active
- 2014-03-11 AU AU2014249050A patent/AU2014249050B2/en not_active Ceased
-
2017
- 2017-07-17 US US15/652,174 patent/US9873697B2/en active Active
- 2017-12-14 US US15/842,700 patent/US10174026B2/en active Active
-
2018
- 2018-11-27 US US16/202,072 patent/US10494369B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| AU2014249050B2 (en) | 2017-10-05 |
| US9873697B2 (en) | 2018-01-23 |
| US9738637B2 (en) | 2017-08-22 |
| WO2014164708A1 (en) | 2014-10-09 |
| EP2968282A4 (en) | 2016-08-24 |
| EP2968282A1 (en) | 2016-01-20 |
| JP2016516699A (ja) | 2016-06-09 |
| US20170313702A1 (en) | 2017-11-02 |
| US20180105521A1 (en) | 2018-04-19 |
| US10174026B2 (en) | 2019-01-08 |
| AU2014249050A1 (en) | 2015-09-17 |
| US20190092771A1 (en) | 2019-03-28 |
| US10494369B2 (en) | 2019-12-03 |
| EP2968282B1 (en) | 2018-05-09 |
| US20160194315A1 (en) | 2016-07-07 |
| JP6320506B2 (ja) | 2018-05-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2014249050B2 (en) | Histone dementhylase inhibitors | |
| AU2013361255B2 (en) | Histone demethylase inhibitors | |
| AU2013363957B2 (en) | Histone demethylase inhibitors | |
| JP6552608B2 (ja) | ヒストンデメチラーゼ阻害剤 | |
| RS62874B1 (sr) | Inhibitori lizin specifične demetilaze-1 | |
| JP6967632B2 (ja) | ヒストンデメチラーゼ阻害剤 | |
| JP2019508452A (ja) | ヒストンデメチラーゼ阻害剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |
Effective date: 20200311 |