CN101918389A - 组蛋白脱乙酰酶抑制剂 - Google Patents
组蛋白脱乙酰酶抑制剂 Download PDFInfo
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- CN101918389A CN101918389A CN2008801238575A CN200880123857A CN101918389A CN 101918389 A CN101918389 A CN 101918389A CN 2008801238575 A CN2008801238575 A CN 2008801238575A CN 200880123857 A CN200880123857 A CN 200880123857A CN 101918389 A CN101918389 A CN 101918389A
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- CN
- China
- Prior art keywords
- aryl
- alkyl
- heteroaryl
- hydrocarbyl
- heterocyclyl
- Prior art date
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- 239000003276 histone deacetylase inhibitor Substances 0.000 title description 21
- 229940121372 histone deacetylase inhibitor Drugs 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 265
- -1 N-oxide compound Chemical class 0.000 claims abstract description 176
- 108090000353 Histone deacetylase Proteins 0.000 claims abstract description 113
- 238000000034 method Methods 0.000 claims abstract description 78
- 239000000203 mixture Substances 0.000 claims abstract description 67
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 230000000694 effects Effects 0.000 claims abstract description 37
- 239000000651 prodrug Substances 0.000 claims abstract description 33
- 229940002612 prodrug Drugs 0.000 claims abstract description 33
- 239000012453 solvate Substances 0.000 claims abstract description 20
- 125000003118 aryl group Chemical group 0.000 claims description 402
- 125000000623 heterocyclic group Chemical group 0.000 claims description 347
- 125000001072 heteroaryl group Chemical group 0.000 claims description 334
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 202
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 163
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 126
- 125000001424 substituent group Chemical group 0.000 claims description 124
- 125000001544 thienyl group Chemical group 0.000 claims description 101
- 125000000217 alkyl group Chemical group 0.000 claims description 100
- 125000005843 halogen group Chemical group 0.000 claims description 88
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 81
- 229920006395 saturated elastomer Polymers 0.000 claims description 68
- 150000003254 radicals Chemical class 0.000 claims description 49
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 40
- 229910052757 nitrogen Inorganic materials 0.000 claims description 38
- 125000003342 alkenyl group Chemical group 0.000 claims description 34
- 230000002401 inhibitory effect Effects 0.000 claims description 34
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 34
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 32
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims description 32
- 102100038720 Histone deacetylase 9 Human genes 0.000 claims description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 claims description 29
- 201000010099 disease Diseases 0.000 claims description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
- 125000000304 alkynyl group Chemical group 0.000 claims description 28
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 28
- 125000000335 thiazolyl group Chemical group 0.000 claims description 28
- 239000003112 inhibitor Substances 0.000 claims description 27
- 125000004076 pyridyl group Chemical group 0.000 claims description 27
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 26
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 24
- 239000000126 substance Substances 0.000 claims description 24
- 150000001204 N-oxides Chemical class 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000006239 protecting group Chemical group 0.000 claims description 23
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 102100021454 Histone deacetylase 4 Human genes 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- 102100021453 Histone deacetylase 5 Human genes 0.000 claims description 15
- 101000899259 Homo sapiens Histone deacetylase 4 Proteins 0.000 claims description 15
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 15
- 125000005605 benzo group Chemical group 0.000 claims description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 102100022537 Histone deacetylase 6 Human genes 0.000 claims description 14
- 101000899255 Homo sapiens Histone deacetylase 5 Proteins 0.000 claims description 14
- 229910003827 NRaRb Inorganic materials 0.000 claims description 14
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 14
- 101000899330 Homo sapiens Histone deacetylase 6 Proteins 0.000 claims description 13
- 101001032113 Homo sapiens Histone deacetylase 7 Proteins 0.000 claims description 13
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 13
- WWGBHDIHIVGYLZ-UHFFFAOYSA-N N-[4-[3-[[[7-(hydroxyamino)-7-oxoheptyl]amino]-oxomethyl]-5-isoxazolyl]phenyl]carbamic acid tert-butyl ester Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1C1=CC(C(=O)NCCCCCCC(=O)NO)=NO1 WWGBHDIHIVGYLZ-UHFFFAOYSA-N 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 13
- 125000002971 oxazolyl group Chemical group 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 102100038715 Histone deacetylase 8 Human genes 0.000 claims description 11
- 101001032092 Homo sapiens Histone deacetylase 9 Proteins 0.000 claims description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 125000003107 substituted aryl group Chemical group 0.000 claims description 11
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 11
- WXLCDTBTIVJDCE-UHFFFAOYSA-N 1,4-oxazepine Chemical compound O1C=CC=NC=C1 WXLCDTBTIVJDCE-UHFFFAOYSA-N 0.000 claims description 10
- 101001032118 Homo sapiens Histone deacetylase 8 Proteins 0.000 claims description 10
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000003386 piperidinyl group Chemical group 0.000 claims description 9
- 150000004677 hydrates Chemical class 0.000 claims description 8
- ZHSDLNXUORTYIN-UHFFFAOYSA-N n-hydroxy-2-phenylbenzamide Chemical compound ONC(=O)C1=CC=CC=C1C1=CC=CC=C1 ZHSDLNXUORTYIN-UHFFFAOYSA-N 0.000 claims description 8
- VVTCLTONLVZMDI-UHFFFAOYSA-N 2-anilino-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC=CC=C1NC1=CC=CC=C1 VVTCLTONLVZMDI-UHFFFAOYSA-N 0.000 claims description 7
- UCFKRCOAJVNWLW-UHFFFAOYSA-N 2-benzyl-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC=CC=C1CC1=CC=CC=C1 UCFKRCOAJVNWLW-UHFFFAOYSA-N 0.000 claims description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 7
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 7
- BAVHJZLGCYAXHZ-UHFFFAOYSA-N n-hydroxy-2-phenoxybenzamide Chemical compound ONC(=O)C1=CC=CC=C1OC1=CC=CC=C1 BAVHJZLGCYAXHZ-UHFFFAOYSA-N 0.000 claims description 7
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 6
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 238000006467 substitution reaction Methods 0.000 claims description 6
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 5
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 5
- FTBBGQKRYUTLMP-UHFFFAOYSA-N 2-nitro-1h-pyrrole Chemical compound [O-][N+](=O)C1=CC=CN1 FTBBGQKRYUTLMP-UHFFFAOYSA-N 0.000 claims description 4
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- NPUACKRELIJTFM-UHFFFAOYSA-N cr gas Chemical class C1=NC2=CC=CC=C2OC2=CC=CC=C21 NPUACKRELIJTFM-UHFFFAOYSA-N 0.000 claims description 2
- QNISXNPVLHARBE-UHFFFAOYSA-N n-hydroxy-4-naphthalen-1-yl-1h-pyrrole-3-carboxamide Chemical compound ONC(=O)C1=CNC=C1C1=CC=CC2=CC=CC=C12 QNISXNPVLHARBE-UHFFFAOYSA-N 0.000 claims description 2
- BRFCXCIMFPFJPQ-UHFFFAOYSA-N n-hydroxy-4-naphthalen-2-yl-1h-pyrrole-3-carboxamide Chemical compound ONC(=O)C1=CNC=C1C1=CC=C(C=CC=C2)C2=C1 BRFCXCIMFPFJPQ-UHFFFAOYSA-N 0.000 claims description 2
- UUZPASUWMAPZET-UHFFFAOYSA-N n-hydroxy-4-phenyl-1h-pyrrole-3-carboxamide Chemical compound ONC(=O)C1=CNC=C1C1=CC=CC=C1 UUZPASUWMAPZET-UHFFFAOYSA-N 0.000 claims description 2
- 230000004044 response Effects 0.000 claims description 2
- 125000005936 piperidyl group Chemical group 0.000 claims 2
- 102000003964 Histone deacetylase Human genes 0.000 abstract description 104
- 230000006340 racemization Effects 0.000 abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 166
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- 239000000243 solution Substances 0.000 description 72
- 235000019439 ethyl acetate Nutrition 0.000 description 65
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 61
- 239000007787 solid Substances 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- 239000011541 reaction mixture Substances 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 239000000758 substrate Substances 0.000 description 31
- 239000012267 brine Substances 0.000 description 27
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 24
- 238000000746 purification Methods 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- 125000004043 oxo group Chemical group O=* 0.000 description 23
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 22
- 125000004093 cyano group Chemical group *C#N 0.000 description 21
- 125000000392 cycloalkenyl group Chemical group 0.000 description 21
- 229910052938 sodium sulfate Inorganic materials 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 20
- 125000004432 carbon atom Chemical group C* 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 15
- 229940127271 compound 49 Drugs 0.000 description 15
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- 230000005764 inhibitory process Effects 0.000 description 14
- 125000002947 alkylene group Chemical group 0.000 description 13
- 238000001727 in vivo Methods 0.000 description 13
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- 239000007832 Na2SO4 Substances 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 125000003003 spiro group Chemical group 0.000 description 12
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- 125000003710 aryl alkyl group Chemical group 0.000 description 11
- 125000002619 bicyclic group Chemical group 0.000 description 11
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- 125000000524 functional group Chemical group 0.000 description 11
- 239000006260 foam Substances 0.000 description 10
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- 125000003367 polycyclic group Chemical group 0.000 description 10
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- 241001465754 Metazoa Species 0.000 description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
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- 239000001257 hydrogen Substances 0.000 description 9
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- JNRZEKVYDKHDEC-UHFFFAOYSA-N n-hydroxy-3,5-diphenylthiophene-2-carboxamide Chemical compound ONC(=O)C=1SC(C=2C=CC=CC=2)=CC=1C1=CC=CC=C1 JNRZEKVYDKHDEC-UHFFFAOYSA-N 0.000 description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 125000002252 acyl group Chemical group 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 7
- 230000004071 biological effect Effects 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 125000002541 furyl group Chemical group 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 125000004434 sulfur atom Chemical group 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- 102100039385 Histone deacetylase 11 Human genes 0.000 description 6
- 102000006947 Histones Human genes 0.000 description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 125000004442 acylamino group Chemical group 0.000 description 6
- 125000001931 aliphatic group Chemical group 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical class OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
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- VJJIJPXUIIDFPM-UHFFFAOYSA-N 5-[[benzyl(methyl)amino]methyl]-n-hydroxy-3-phenylthiophene-2-carboxamide Chemical compound C=1C=CC=CC=1CN(C)CC(SC=1C(=O)NO)=CC=1C1=CC=CC=C1 VJJIJPXUIIDFPM-UHFFFAOYSA-N 0.000 description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
- 108010077544 Chromatin Proteins 0.000 description 5
- 108091005772 HDAC11 Proteins 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 5
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 210000003483 chromatin Anatomy 0.000 description 5
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- 125000002883 imidazolyl group Chemical group 0.000 description 5
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 125000006413 ring segment Chemical group 0.000 description 5
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 4
- JKUJWDQRAHMNSN-UHFFFAOYSA-N 2-n-hydroxy-5-n,3-diphenylthiophene-2,5-dicarboxamide Chemical compound ONC(=O)C=1SC(C(=O)NC=2C=CC=CC=2)=CC=1C1=CC=CC=C1 JKUJWDQRAHMNSN-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000021736 acetylation Effects 0.000 description 4
- 125000005024 alkenyl aryl group Chemical group 0.000 description 4
- 125000001118 alkylidene group Chemical group 0.000 description 4
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 4
- 125000004103 aminoalkyl group Chemical group 0.000 description 4
- 239000000074 antisense oligonucleotide Substances 0.000 description 4
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- 125000003588 lysine group Chemical group [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 1
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- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
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- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
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- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 description 1
- CZOMFXPIHFKTIK-UHFFFAOYSA-N methyl 1-(2,4-dichlorophenyl)-5-(3-morpholin-4-ylphenyl)pyrazole-3-carboxylate Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1N=C(C(=O)OC)C=C1C(C=1)=CC=CC=1N1CCOCC1 CZOMFXPIHFKTIK-UHFFFAOYSA-N 0.000 description 1
- BXPQSKLKHBMONW-UHFFFAOYSA-N methyl 1-(2,4-dichlorophenyl)-5-[3-(2,3-dihydroindol-1-yl)phenyl]pyrazole-3-carboxylate Chemical compound N1=C(C(=O)OC)C=C(C=2C=C(C=CC=2)N2C3=CC=CC=C3CC2)N1C1=CC=C(Cl)C=C1Cl BXPQSKLKHBMONW-UHFFFAOYSA-N 0.000 description 1
- NDZFJYPBTXICNN-UHFFFAOYSA-N methyl 1-benzyl-5-(3-bromophenyl)pyrazole-3-carboxylate Chemical compound C=1C=CC=CC=1CN1N=C(C(=O)OC)C=C1C1=CC=CC(Br)=C1 NDZFJYPBTXICNN-UHFFFAOYSA-N 0.000 description 1
- GURLLWMMDLGOBF-UHFFFAOYSA-N methyl 1-benzyl-5-(3-morpholin-4-ylphenyl)pyrazole-3-carboxylate Chemical compound C=1C=CC=CC=1CN1N=C(C(=O)OC)C=C1C(C=1)=CC=CC=1N1CCOCC1 GURLLWMMDLGOBF-UHFFFAOYSA-N 0.000 description 1
- HPOPSJUQHAPJER-UHFFFAOYSA-N methyl 2-(2-phenylethynyl)benzoate Chemical compound COC(=O)C1=CC=CC=C1C#CC1=CC=CC=C1 HPOPSJUQHAPJER-UHFFFAOYSA-N 0.000 description 1
- VRTQLDFCPNVQNT-UHFFFAOYSA-N methyl 2-bromo-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1Br VRTQLDFCPNVQNT-UHFFFAOYSA-N 0.000 description 1
- SWGQITQOBPXVRC-UHFFFAOYSA-N methyl 2-bromobenzoate Chemical compound COC(=O)C1=CC=CC=C1Br SWGQITQOBPXVRC-UHFFFAOYSA-N 0.000 description 1
- HUNUAFNLLYVTQD-UHFFFAOYSA-N methyl 2-chlorosulfonylbenzoate Chemical compound COC(=O)C1=CC=CC=C1S(Cl)(=O)=O HUNUAFNLLYVTQD-UHFFFAOYSA-N 0.000 description 1
- WNAFVJVEADYQAI-UHFFFAOYSA-N methyl 2-phenylbenzoate Chemical compound COC(=O)C1=CC=CC=C1C1=CC=CC=C1 WNAFVJVEADYQAI-UHFFFAOYSA-N 0.000 description 1
- UEHVYCSHYVHJKC-UHFFFAOYSA-N methyl 3-(3-bromophenyl)-1h-pyrazole-5-carboxylate Chemical compound N1C(C(=O)OC)=CC(C=2C=C(Br)C=CC=2)=N1 UEHVYCSHYVHJKC-UHFFFAOYSA-N 0.000 description 1
- HGLVYXXPRSNKQN-UHFFFAOYSA-N methyl 3-(4-fluorophenyl)-3-oxopropanoate Chemical compound COC(=O)CC(=O)C1=CC=C(F)C=C1 HGLVYXXPRSNKQN-UHFFFAOYSA-N 0.000 description 1
- NDVLANPSKUKWGI-UHFFFAOYSA-N methyl 3-[3-[3-(trifluoromethyl)phenyl]phenyl]-1H-pyrazole-5-carboxylate Chemical compound N1N=C(C(=O)OC)C=C1C1=CC=CC(C=2C=C(C=CC=2)C(F)(F)F)=C1 NDVLANPSKUKWGI-UHFFFAOYSA-N 0.000 description 1
- QESSCNMSOLRYBO-UHFFFAOYSA-N methyl 3-amino-5-phenylthiophene-2-carboxylate Chemical compound NC1=C(C(=O)OC)SC(C=2C=CC=CC=2)=C1 QESSCNMSOLRYBO-UHFFFAOYSA-N 0.000 description 1
- IHAFEVZYEBKJDG-UHFFFAOYSA-N methyl 3-phenyl-1-benzothiophene-2-carboxylate Chemical compound COC(=O)C=1SC2=CC=CC=C2C=1C1=CC=CC=C1 IHAFEVZYEBKJDG-UHFFFAOYSA-N 0.000 description 1
- UTONEVNSKHYGED-UHFFFAOYSA-N methyl 4-[(2-phenoxyphenyl)carbamoyl]-2-phenylbenzoate Chemical compound COC(=O)C1=CC=C(C(=O)NC=2C(=CC=CC=2)OC=2C=CC=CC=2)C=C1C1=CC=CC=C1 UTONEVNSKHYGED-UHFFFAOYSA-N 0.000 description 1
- PBEXAYYJBIJRJE-UHFFFAOYSA-N methyl 5-(3-bromophenyl)-1-(2,4-dichlorophenyl)pyrazole-3-carboxylate Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1N=C(C(=O)OC)C=C1C1=CC=CC(Br)=C1 PBEXAYYJBIJRJE-UHFFFAOYSA-N 0.000 description 1
- SUGOXAOIFOULRS-UHFFFAOYSA-N methyl 5-(3-bromophenyl)-1-[3-(trifluoromethyl)phenyl]pyrazole-3-carboxylate Chemical compound C=1C=CC(C(F)(F)F)=CC=1N1N=C(C(=O)OC)C=C1C1=CC=CC(Br)=C1 SUGOXAOIFOULRS-UHFFFAOYSA-N 0.000 description 1
- FUQFQKNNGIPCGG-UHFFFAOYSA-N methyl 5-(3-bromophenyl)-1-phenylpyrazole-3-carboxylate Chemical compound C=1C=CC=CC=1N1N=C(C(=O)OC)C=C1C1=CC=CC(Br)=C1 FUQFQKNNGIPCGG-UHFFFAOYSA-N 0.000 description 1
- FAALYPCLYUVVCH-UHFFFAOYSA-N methyl 5-(3-bromophenyl)-1-tert-butylpyrazole-3-carboxylate Chemical compound CC(C)(C)N1N=C(C(=O)OC)C=C1C1=CC=CC(Br)=C1 FAALYPCLYUVVCH-UHFFFAOYSA-N 0.000 description 1
- PBMRWZSAKHEGJR-UHFFFAOYSA-N methyl 5-(3-morpholin-4-ylphenyl)-1-[3-(trifluoromethyl)phenyl]pyrazole-3-carboxylate Chemical compound C=1C=CC(C(F)(F)F)=CC=1N1N=C(C(=O)OC)C=C1C(C=1)=CC=CC=1N1CCOCC1 PBMRWZSAKHEGJR-UHFFFAOYSA-N 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- HCOVEUUIZWEZBK-UHFFFAOYSA-N n-(2,2-diethoxyethyl)formamide Chemical compound CCOC(OCC)CNC=O HCOVEUUIZWEZBK-UHFFFAOYSA-N 0.000 description 1
- FTQWRYSLUYAIRQ-UHFFFAOYSA-N n-[(octadecanoylamino)methyl]octadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NCNC(=O)CCCCCCCCCCCCCCCCC FTQWRYSLUYAIRQ-UHFFFAOYSA-N 0.000 description 1
- LPOIGVZLNWEGJG-UHFFFAOYSA-N n-benzyl-5-(4-methylpiperazin-1-yl)-2-nitroaniline Chemical compound C1CN(C)CCN1C1=CC=C([N+]([O-])=O)C(NCC=2C=CC=CC=2)=C1 LPOIGVZLNWEGJG-UHFFFAOYSA-N 0.000 description 1
- JQEOVBCRVVKIGH-UHFFFAOYSA-N n-hydroxy-2-(2-phenylethyl)benzamide Chemical compound ONC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 JQEOVBCRVVKIGH-UHFFFAOYSA-N 0.000 description 1
- QUVCJUGNXPANOI-UHFFFAOYSA-N n-hydroxy-5-(3-morpholin-4-ylphenyl)-1-[3-(trifluoromethyl)phenyl]pyrazole-3-carboxamide Chemical compound C=1C=CC(C(F)(F)F)=CC=1N1N=C(C(=O)NO)C=C1C(C=1)=CC=CC=1N1CCOCC1 QUVCJUGNXPANOI-UHFFFAOYSA-N 0.000 description 1
- OUNHKPGNTJDPON-UHFFFAOYSA-N n-hydroxy-5-(3-morpholin-4-ylphenyl)-1-phenylpyrazole-3-carboxamide Chemical compound C=1C=CC=CC=1N1N=C(C(=O)NO)C=C1C(C=1)=CC=CC=1N1CCOCC1 OUNHKPGNTJDPON-UHFFFAOYSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 150000002814 niacins Chemical class 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 210000001623 nucleosome Anatomy 0.000 description 1
- 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000003901 oxalic acid esters Chemical class 0.000 description 1
- QNNHQVPFZIFNFK-UHFFFAOYSA-N oxazolo[4,5-b]pyridine Chemical compound C1=CC=C2OC=NC2=N1 QNNHQVPFZIFNFK-UHFFFAOYSA-N 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L persulfate group Chemical group S(=O)(=O)([O-])OOS(=O)(=O)[O-] JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 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
- GJSGGHOYGKMUPT-UHFFFAOYSA-N phenoxathiine Chemical compound C1=CC=C2OC3=CC=CC=C3SC2=C1 GJSGGHOYGKMUPT-UHFFFAOYSA-N 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical class CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000005633 phthalidyl group Chemical group 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 125000004928 piperidonyl group Chemical group 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
- 125000005547 pivalate group Chemical group 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000006410 propenylene group Chemical group 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- YEYHFKBVNARCNE-UHFFFAOYSA-N pyrido[2,3-b]pyrazine Chemical compound N1=CC=NC2=CC=CN=C21 YEYHFKBVNARCNE-UHFFFAOYSA-N 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 230000035936 sexual power Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
- JNJJINIJWXHEQQ-UHFFFAOYSA-N tert-butyl n-(2-amino-4-thiophen-2-ylphenyl)carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC=C1C1=CC=CS1 JNJJINIJWXHEQQ-UHFFFAOYSA-N 0.000 description 1
- KEZUHKOOIQKEIT-UHFFFAOYSA-N tert-butyl n-(2-nitro-4-thiophen-2-ylphenyl)carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=C1C1=CC=CS1 KEZUHKOOIQKEIT-UHFFFAOYSA-N 0.000 description 1
- SUTRDULVNIPNLW-SFHVURJKSA-N tert-butyl n-[(2s)-6-acetamido-1-[(4-methyl-2-oxochromen-7-yl)amino]-1-oxohexan-2-yl]carbamate Chemical compound CC1=CC(=O)OC2=CC(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CCCCNC(=O)C)=CC=C21 SUTRDULVNIPNLW-SFHVURJKSA-N 0.000 description 1
- ZYDKYFIXEYSNPO-UHFFFAOYSA-N tert-butyl-dimethyl-prop-2-ynoxysilane Chemical compound CC(C)(C)[Si](C)(C)OCC#C ZYDKYFIXEYSNPO-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- DDPWVABNMBRBFI-UHFFFAOYSA-N tert-butylhydrazine;hydron;chloride Chemical compound Cl.CC(C)(C)NN DDPWVABNMBRBFI-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000006092 tetrahydro-1,1-dioxothienyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 229940124788 therapeutic inhibitor Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 150000003567 thiocyanates Chemical class 0.000 description 1
- 125000005505 thiomorpholino group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- ZCAGUOCUDGWENZ-UHFFFAOYSA-N thiomorpholinyl sulfoxide group Chemical group N1(CCSCC1)S(=O)N1CCSCC1 ZCAGUOCUDGWENZ-UHFFFAOYSA-N 0.000 description 1
- ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 102000003306 transcription coregulator activity proteins Human genes 0.000 description 1
- 108040010337 transcription coregulator activity proteins Proteins 0.000 description 1
- 108091006107 transcriptional repressors Proteins 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229960000363 trapidil Drugs 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- 125000000169 tricyclic heterocycle group Chemical group 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical group 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/10—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/587—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with aliphatic hydrocarbon radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms, said aliphatic radicals being substituted in the alpha-position to the ring by a hetero atom, e.g. with m >= 0, Z being a singly or a doubly bound hetero atom
- C07D277/593—Z being doubly bound oxygen or doubly bound nitrogen, which nitrogen is part of a possibly substituted oximino radical
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
- C07D207/327—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102775368A (zh) * | 2011-05-10 | 2012-11-14 | 中国科学院上海药物研究所 | 一类噻唑类化合物及其制备方法和用途 |
| CN109232426A (zh) * | 2018-10-18 | 2019-01-18 | 中国药科大学 | 一种n-羟基-5-取代-1h-吡唑-3-甲酰胺化合物及其制备方法和用途 |
| CN109574936A (zh) * | 2018-11-23 | 2019-04-05 | 沈阳药科大学 | 一种具有hdac6抑制活性的异羟肟酸类化合物及其应用 |
| WO2021208945A1 (zh) * | 2020-04-17 | 2021-10-21 | 上海中泽医药科技有限公司 | 一种苯并氮杂环类化合物、其制备方法及用途 |
| CN117263936A (zh) * | 2023-11-21 | 2023-12-22 | 中国中医科学院医学实验中心 | 一种咪唑并[1, 2-a]吡啶衍生物及其制备方法和在中枢神经系统渗透性HDAC6抑制药物中的应用 |
| CN118515623A (zh) * | 2024-04-26 | 2024-08-20 | 河北中医药大学 | 一种取代苯并异恶唑类化合物及其在制备抗肿瘤药物中的应用 |
Families Citing this family (88)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8563573B2 (en) | 2007-11-02 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Azaindole derivatives as CFTR modulators |
| US9187485B2 (en) | 2007-02-02 | 2015-11-17 | Baylor College Of Medicine | Methods and compositions for the treatment of cancer and related hyperproliferative disorders |
| CN102482249B (zh) | 2009-07-08 | 2016-06-08 | 德米拉(加拿大)公司 | 用于治疗皮肤病症或疾病状态的tofa类似物 |
| EP2305643A1 (en) * | 2009-10-02 | 2011-04-06 | Ikerchem, S.L. | New histone deacetylase inhibitors based simultaneously on trisubstituted 1h-pyrroles and aromatic and heteroaromatic spacers |
| US8802868B2 (en) | 2010-03-25 | 2014-08-12 | Vertex Pharmaceuticals Incorporated | Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide |
| MX353408B (es) | 2010-04-22 | 2018-01-11 | Vertex Pharma | Proceso para producir compuestos de cicloalquilcarboxamido-indol. |
| WO2011145669A1 (ja) * | 2010-05-19 | 2011-11-24 | 大日本住友製薬株式会社 | アミド誘導体 |
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Also Published As
| Publication number | Publication date |
|---|---|
| KR20100095430A (ko) | 2010-08-30 |
| EP2217588A1 (en) | 2010-08-18 |
| RU2010122304A (ru) | 2011-12-10 |
| AU2008318244A1 (en) | 2009-05-07 |
| JP2011502133A (ja) | 2011-01-20 |
| WO2009055917A1 (en) | 2009-05-07 |
| US20140045850A1 (en) | 2014-02-13 |
| BRPI0817897A2 (pt) | 2019-09-24 |
| RU2501787C2 (ru) | 2013-12-20 |
| US8673911B2 (en) | 2014-03-18 |
| CA2703718A1 (en) | 2009-05-07 |
| US20110021771A1 (en) | 2011-01-27 |
| EP2217588A4 (en) | 2013-12-04 |
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