JP2011502133A - ヒストンデアセチラーゼの阻害剤 - Google Patents
ヒストンデアセチラーゼの阻害剤 Download PDFInfo
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- JP2011502133A JP2011502133A JP2010531384A JP2010531384A JP2011502133A JP 2011502133 A JP2011502133 A JP 2011502133A JP 2010531384 A JP2010531384 A JP 2010531384A JP 2010531384 A JP2010531384 A JP 2010531384A JP 2011502133 A JP2011502133 A JP 2011502133A
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- JP
- Japan
- Prior art keywords
- alkyl
- aryl
- heteroaryl
- heterocyclyl
- phenyl
- 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.)
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- 108090000353 Histone deacetylase Proteins 0.000 title claims abstract description 103
- 239000003112 inhibitor Substances 0.000 title claims description 30
- 102000003964 Histone deacetylase Human genes 0.000 title abstract description 96
- 150000001875 compounds Chemical class 0.000 claims abstract description 295
- 150000003839 salts Chemical class 0.000 claims abstract description 121
- 238000000034 method Methods 0.000 claims abstract description 71
- 239000000203 mixture Substances 0.000 claims abstract description 71
- 230000000694 effects Effects 0.000 claims abstract description 41
- 229940002612 prodrug Drugs 0.000 claims abstract description 33
- 239000000651 prodrug Substances 0.000 claims abstract description 33
- 239000012453 solvate Substances 0.000 claims abstract description 20
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 18
- 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 abstract description 10
- 150000004677 hydrates Chemical class 0.000 claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 claims description 460
- 125000001072 heteroaryl group Chemical group 0.000 claims description 370
- 125000000623 heterocyclic group Chemical group 0.000 claims description 351
- 125000000217 alkyl group Chemical group 0.000 claims description 238
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 221
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 169
- -1 spiroheterocyclyl Chemical group 0.000 claims description 135
- 125000001424 substituent group Chemical group 0.000 claims description 122
- 125000001544 thienyl group Chemical group 0.000 claims description 102
- 125000005843 halogen group Chemical group 0.000 claims description 93
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 87
- 229920006395 saturated elastomer Polymers 0.000 claims description 72
- 125000003545 alkoxy group Chemical group 0.000 claims description 62
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 58
- 125000003342 alkenyl group Chemical group 0.000 claims description 43
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 42
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 41
- 229910052757 nitrogen Inorganic materials 0.000 claims description 38
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 33
- 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
- 201000010099 disease Diseases 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 239000000126 substance Substances 0.000 claims description 32
- 125000000304 alkynyl group Chemical group 0.000 claims description 30
- 229910052799 carbon Inorganic materials 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 230000002401 inhibitory effect Effects 0.000 claims description 29
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 29
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 28
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 28
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 27
- 125000004076 pyridyl group Chemical group 0.000 claims description 27
- 125000000335 thiazolyl group Chemical group 0.000 claims description 27
- 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 26
- 125000004122 cyclic group Chemical group 0.000 claims description 24
- 125000006239 protecting group Chemical group 0.000 claims description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 21
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 18
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 17
- 102100021454 Histone deacetylase 4 Human genes 0.000 claims description 16
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
- 102100021453 Histone deacetylase 5 Human genes 0.000 claims description 15
- 101000899259 Homo sapiens Histone deacetylase 4 Proteins 0.000 claims description 15
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 15
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 15
- NPUACKRELIJTFM-UHFFFAOYSA-N cr gas Chemical compound C1=NC2=CC=CC=C2OC2=CC=CC=C21 NPUACKRELIJTFM-UHFFFAOYSA-N 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 15
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-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
- 101001032113 Homo sapiens Histone deacetylase 7 Proteins 0.000 claims description 14
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 14
- 102100038715 Histone deacetylase 8 Human genes 0.000 claims description 13
- 101000899330 Homo sapiens Histone deacetylase 6 Proteins 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
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 101001032118 Homo sapiens Histone deacetylase 8 Proteins 0.000 claims description 12
- 101001032092 Homo sapiens Histone deacetylase 9 Proteins 0.000 claims description 12
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 12
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 11
- 125000003386 piperidinyl group Chemical group 0.000 claims description 11
- 125000003107 substituted aryl group Chemical group 0.000 claims description 11
- 102100039385 Histone deacetylase 11 Human genes 0.000 claims description 10
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
- 125000002971 oxazolyl group Chemical group 0.000 claims description 10
- 108091005772 HDAC11 Proteins 0.000 claims description 9
- 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 9
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 9
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 8
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 8
- OXMPDOZBQGHTGH-UHFFFAOYSA-N 5h-benzo[b][1,4]benzoxazepin-6-one Chemical compound O=C1NC2=CC=CC=C2OC2=CC=CC=C12 OXMPDOZBQGHTGH-UHFFFAOYSA-N 0.000 claims description 7
- WGIAUTGOUJDVEI-UHFFFAOYSA-N 2-phenylpiperidine Chemical compound N1CCCCC1C1=CC=CC=C1 WGIAUTGOUJDVEI-UHFFFAOYSA-N 0.000 claims description 6
- HCUOEKSZWPGJIM-IYNMRSRQSA-N (e,2z)-2-hydroxyimino-6-methoxy-4-methyl-5-nitrohex-3-enamide Chemical compound COCC([N+]([O-])=O)\C(C)=C\C(=N\O)\C(N)=O HCUOEKSZWPGJIM-IYNMRSRQSA-N 0.000 claims description 5
- 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 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 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 4
- FTBBGQKRYUTLMP-UHFFFAOYSA-N 2-nitro-1h-pyrrole Chemical group [O-][N+](=O)C1=CC=CN1 FTBBGQKRYUTLMP-UHFFFAOYSA-N 0.000 claims description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 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
- 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 4
- 125000005599 alkyl carboxylate group Chemical group 0.000 claims description 2
- 239000013522 chelant Substances 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
- JKWQUMKCVDUICQ-UHFFFAOYSA-N 2-anilinobenzamide Chemical compound NC(=O)C1=CC=CC=C1NC1=CC=CC=C1 JKWQUMKCVDUICQ-UHFFFAOYSA-N 0.000 claims 1
- CJCOBMTYEDBBSY-UHFFFAOYSA-N 2-phenoxybenzamide Chemical compound NC(=O)C1=CC=CC=C1OC1=CC=CC=C1 CJCOBMTYEDBBSY-UHFFFAOYSA-N 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 abstract description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 163
- ILYSAKHOYBPSPC-UHFFFAOYSA-N 2-phenylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=CC=C1 ILYSAKHOYBPSPC-UHFFFAOYSA-N 0.000 description 155
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 121
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 67
- 235000019439 ethyl acetate Nutrition 0.000 description 64
- 239000000243 solution Substances 0.000 description 63
- 239000007787 solid Substances 0.000 description 47
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- 239000011541 reaction mixture Substances 0.000 description 36
- 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
- 210000004027 cell Anatomy 0.000 description 26
- 238000000746 purification Methods 0.000 description 25
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 125000004043 oxo group Chemical group O=* 0.000 description 24
- 230000002829 reductive effect Effects 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 125000004093 cyano group Chemical group *C#N 0.000 description 23
- 125000000392 cycloalkenyl group Chemical group 0.000 description 22
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 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 20
- 238000006243 chemical reaction Methods 0.000 description 19
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 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 18
- 239000011734 sodium Substances 0.000 description 18
- 239000002904 solvent Substances 0.000 description 17
- 125000003367 polycyclic group Chemical group 0.000 description 16
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 15
- 125000003710 aryl alkyl group Chemical group 0.000 description 15
- 0 C*N(*C*(C)C*(*)CC1)C1N Chemical compound C*N(*C*(C)C*(*)CC1)C1N 0.000 description 13
- 125000002947 alkylene group Chemical group 0.000 description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 13
- 125000002252 acyl group Chemical group 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 108010033040 Histones Proteins 0.000 description 11
- 241000124008 Mammalia Species 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 125000003282 alkyl amino group Chemical group 0.000 description 11
- 125000002619 bicyclic group Chemical group 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 239000006260 foam Substances 0.000 description 10
- 125000000524 functional group Chemical group 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 125000003003 spiro group Chemical group 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 241001465754 Metazoa Species 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
- 239000002253 acid Substances 0.000 description 9
- 125000004103 aminoalkyl group Chemical group 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 7
- 125000004442 acylamino group Chemical group 0.000 description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- QQBSHUCUXPPCEI-UHFFFAOYSA-N ethyl 2-[3-[(2-methylpropan-2-yl)oxycarbonyl]phenyl]benzoate Chemical compound CCOC(=O)C1=CC=CC=C1C1=CC=CC(C(=O)OC(C)(C)C)=C1 QQBSHUCUXPPCEI-UHFFFAOYSA-N 0.000 description 7
- 125000002541 furyl group Chemical group 0.000 description 7
- 125000001183 hydrocarbyl group Chemical group 0.000 description 7
- 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 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- UDTZIWZNHBUASM-UHFFFAOYSA-N n-hydroxy-2-(2-phenylethynyl)benzamide Chemical compound ONC(=O)C1=CC=CC=C1C#CC1=CC=CC=C1 UDTZIWZNHBUASM-UHFFFAOYSA-N 0.000 description 7
- 125000005429 oxyalkyl group Chemical group 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 125000000547 substituted alkyl group Chemical group 0.000 description 7
- 125000004434 sulfur atom Chemical group 0.000 description 7
- GBQRBWMCODWHSI-UHFFFAOYSA-N 3-(2-ethoxycarbonylphenyl)benzoic acid Chemical compound CCOC(=O)C1=CC=CC=C1C1=CC=CC(C(O)=O)=C1 GBQRBWMCODWHSI-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-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
- 125000001931 aliphatic group Chemical group 0.000 description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 6
- 230000001668 ameliorated effect Effects 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- 238000009833 condensation Methods 0.000 description 6
- 230000005494 condensation Effects 0.000 description 6
- HHQLRYWKTVNRMX-UHFFFAOYSA-N ethyl 2,5-diphenylthiophene-3-carboxylate Chemical compound CCOC(=O)C=1C=C(C=2C=CC=CC=2)SC=1C1=CC=CC=C1 HHQLRYWKTVNRMX-UHFFFAOYSA-N 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 150000002367 halogens Chemical class 0.000 description 6
- 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 6
- ZMFRWYJGAQDYHT-UHFFFAOYSA-N methyl 2,4-bis(trifluoromethylsulfonyloxy)benzoate Chemical compound COC(=O)C1=CC=C(OS(=O)(=O)C(F)(F)F)C=C1OS(=O)(=O)C(F)(F)F ZMFRWYJGAQDYHT-UHFFFAOYSA-N 0.000 description 6
- BFTXABGSCKCCLI-UHFFFAOYSA-N methyl 2,4-diphenyl-1,3-thiazole-5-carboxylate Chemical compound COC(=O)C=1SC(C=2C=CC=CC=2)=NC=1C1=CC=CC=C1 BFTXABGSCKCCLI-UHFFFAOYSA-N 0.000 description 6
- YQOLFGQIZQAZKK-UHFFFAOYSA-N methyl 2-bromo-3-(4-fluorophenyl)-3-oxopropanoate Chemical compound COC(=O)C(Br)C(=O)C1=CC=C(F)C=C1 YQOLFGQIZQAZKK-UHFFFAOYSA-N 0.000 description 6
- 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 6
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- ZCIIJYZDHKXNNA-UHFFFAOYSA-N ethyl 2-[3-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-thiophen-2-ylphenyl]carbamoyl]phenyl]benzoate Chemical compound CCOC(=O)C1=CC=CC=C1C1=CC=CC(C(=O)NC=2C(=CC=C(C=2)C=2SC=CC=2)NC(=O)OC(C)(C)C)=C1 ZCIIJYZDHKXNNA-UHFFFAOYSA-N 0.000 description 5
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- JXWRMWLJMCPXSS-UHFFFAOYSA-N methyl 2-(benzylsulfamoyl)benzoate Chemical compound COC(=O)C1=CC=CC=C1S(=O)(=O)NCC1=CC=CC=C1 JXWRMWLJMCPXSS-UHFFFAOYSA-N 0.000 description 5
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- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
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- BJPUMTUQINXLGA-UHFFFAOYSA-N 5-methoxycarbonyl-4-phenylthiophene-2-carboxylic acid Chemical compound S1C(C(O)=O)=CC(C=2C=CC=CC=2)=C1C(=O)OC BJPUMTUQINXLGA-UHFFFAOYSA-N 0.000 description 4
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- 125000001820 oxy group Chemical group [*:1]O[*:2] 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
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 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
- 125000005327 perimidinyl group Chemical group N1C(=NC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
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- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
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- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
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- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
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- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
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- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920002643 polyglutamic acid Polymers 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
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- 239000002243 precursor Substances 0.000 description 1
- 125000006410 propenylene group Chemical group 0.000 description 1
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- YEYHFKBVNARCNE-UHFFFAOYSA-N pyrido[2,3-b]pyrazine Chemical compound N1=CC=NC2=CC=CN=C21 YEYHFKBVNARCNE-UHFFFAOYSA-N 0.000 description 1
- JDEUSZPWWMACHZ-UHFFFAOYSA-N pyrido[2,3-e][1,4]diazepin-5-one Chemical compound O=C1N=CC=NC2=NC=CC=C12 JDEUSZPWWMACHZ-UHFFFAOYSA-N 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000004044 response Effects 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
- OHRURASPPZQGQM-UHFFFAOYSA-N romidepsin Natural products O1C(=O)C(C(C)C)NC(=O)C(=CC)NC(=O)C2CSSCCC=CC1CC(=O)NC(C(C)C)C(=O)N2 OHRURASPPZQGQM-UHFFFAOYSA-N 0.000 description 1
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- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 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
- 150000003890 succinate salts Chemical class 0.000 description 1
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- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012385 systemic delivery 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
- SUTRDULVNIPNLW-SFHVURJKSA-N tert-butyl n-[(2s)-6-acetamido-1-[(4-methyl-2-oxochromen-7-yl)amino]-1-oxohexan-2-yl]carbamate Chemical group 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
- 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
- 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
- 125000001412 tetrahydropyranyl group Chemical group 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
- 125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
- 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 125000005505 thiomorpholino group Chemical group 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
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 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
- 108091006105 transcriptional corepressors Proteins 0.000 description 1
- 108091008023 transcriptional regulators Proteins 0.000 description 1
- 108091006107 transcriptional repressors Proteins 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000012384 transportation and delivery Methods 0.000 description 1
- 108010060597 trapoxin A Proteins 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
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 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
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
Classifications
-
- 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
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- 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
- C07D207/34—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 hetero atoms or with 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with 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
- C07D213/61—Halogen atoms or nitro radicals
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/38—One sulfur atom
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- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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| JP2014533734A (ja) * | 2011-11-29 | 2014-12-15 | ナンジン アルゲン ファルマ カンパニー リミテッドNanjing Allgen Pharma Co. Ltd. | Hdac6阻害剤・抗腫瘍剤用複素環アミド化合物 |
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| AR098099A1 (es) | 2013-10-22 | 2016-05-04 | Dow Agrosciences Llc | Composiciones plaguicidas sinérgicas y los métodos relacionados |
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| RU2667777C2 (ru) | 2013-10-22 | 2018-09-24 | ДАУ АГРОСАЙЕНСИЗ ЭлЭлСи | Пестицидные композиции и связанные с ними способы |
| CA2926433A1 (en) | 2013-10-22 | 2015-04-30 | Dow Agrosciences Llc | Pesticidal compositions and related methods |
| TW201519777A (zh) | 2013-10-22 | 2015-06-01 | Dow Agrosciences Llc | 協同性殺蟲組成物及相關方法(九) |
| US9801376B2 (en) | 2013-10-22 | 2017-10-31 | Dow Agrosciences Llc | Synergistic pesticidal compositions and related methods |
| TW201519783A (zh) | 2013-10-22 | 2015-06-01 | Dow Agrosciences Llc | 殺蟲組成物及相關方法(四) |
| WO2015061148A1 (en) | 2013-10-22 | 2015-04-30 | Dow Agrosciences Llc | Synergistic pesticidal compositions and related methods |
| WO2015061146A1 (en) | 2013-10-22 | 2015-04-30 | Dow Agrosciences Llc | Synergistic pesticidal compositions and related methods |
| DE102014203252A1 (de) * | 2014-02-24 | 2015-08-27 | Henkel Ag & Co. Kgaa | Photolabile Duftspeicherstoffe |
| PL3925607T3 (pl) | 2014-04-15 | 2023-10-30 | Vertex Pharmaceuticals Incorporated | Kompozycje farmaceutyczne do leczenia chorób, w których pośredniczy mukowiscydozowy przezbłonowy regulator przewodnictwa |
| US9249122B1 (en) | 2014-07-31 | 2016-02-02 | Dow Agrosciences Llc | Process for the preparation of 3-(3-chloro-1H-pyrazol-1-yl)pyridine |
| BR112017000418A2 (pt) | 2014-07-31 | 2017-11-07 | Dow Agrosciences Llc | processo para a preparação de 3-(3-cloro-1h-pirazol-1-il)piridina |
| JP2017523163A (ja) | 2014-07-31 | 2017-08-17 | ダウ アグロサイエンシィズ エルエルシー | 3−(3−クロロ−1h−ピラゾール−1−イル)ピリジンの製造方法 |
| US9024031B1 (en) | 2014-08-19 | 2015-05-05 | Dow Agrosciences Llc | Process for the preparation of 3-(3-chloro-1H-pyrazol-1-yl)pyridine |
| EP3191455A4 (en) | 2014-09-12 | 2018-01-24 | Dow AgroSciences LLC | Process for the preparation of 3-(3-chloro-1h-pyrazol-1-yl)pyridine |
| US10118890B2 (en) | 2014-10-10 | 2018-11-06 | The Research Foundation For The State University Of New York | Trifluoromethoxylation of arenes via intramolecular trifluoromethoxy group migration |
| WO2016105491A1 (en) | 2014-12-23 | 2016-06-30 | Fgh Biotech | Compositions of fatostatin based heterocyclic compounds and uses thereof |
| WO2016178113A1 (en) | 2015-05-05 | 2016-11-10 | Pfizer Inc. | 2-thiopyrimidinones |
| WO2016202935A1 (en) | 2015-06-19 | 2016-12-22 | Bayer Pharma Aktiengesellschaft | Glucose transport inhibitors |
| US10654814B2 (en) | 2015-12-22 | 2020-05-19 | Kancera Ab | Bicyclic hydroxamic acids useful as inhibitors of mammalian histone deacetylase activity |
| WO2017190086A1 (en) | 2016-04-29 | 2017-11-02 | Fgh Biotech, Inc. | Di-substituted pyrazole compounds for the treatment of diseases |
| WO2018049080A1 (en) | 2016-09-07 | 2018-03-15 | Fgh Biotech, Inc. | Di-substituted pyrazole compounds for the treatment of diseases |
| WO2018075959A1 (en) | 2016-10-20 | 2018-04-26 | Forma Therapeutics, Inc. | Methods using hdac11 inhibitors |
| WO2018125815A1 (en) | 2016-12-29 | 2018-07-05 | Dow Agrosciences Llc | Processes for the preparation of pesticidal compounds |
| WO2018125817A1 (en) | 2016-12-29 | 2018-07-05 | Dow Agrosciences Llc | Processes for the preparation of pesticidal compounds |
| JP2021510152A (ja) * | 2018-01-04 | 2021-04-15 | 北京大学深▲ヂェン▼研究生院Peking University Shenzhen Graduate School | Lsd1とhdacとを標的として同時に阻害する化合物及びその用途 |
| US12128018B2 (en) | 2018-01-12 | 2024-10-29 | KDAc Therapeutics, Inc. | Combination of a selective histone deacetylase 3 (HDAC3) inhibitor and an immunotherapy agent for the treatment of cancer |
| US11535607B2 (en) | 2018-04-20 | 2022-12-27 | Valo Health, Inc. | Isoindolines as HDAC inhibitors |
| EP3853234B1 (en) | 2018-09-18 | 2025-04-23 | Nikang Therapeutics, Inc. | Fused tricyclic ring derivatives as src homology-2 phosphatase inhibitors |
| CN109232426B (zh) * | 2018-10-18 | 2022-09-16 | 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 |
| KR102117083B1 (ko) * | 2018-10-30 | 2020-05-29 | 계명대학교 산학협력단 | 벤조헤테로사이클 화합물 및 이를 유효성분으로 함유하는 암질환 예방 또는 치료용 조성물 |
| CN109574936B (zh) * | 2018-11-23 | 2022-02-22 | 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 |
| CA3165424A1 (en) | 2019-12-20 | 2021-06-24 | Tenaya Therapeutics, Inc. | Fluoroalkyl-oxadiazoles and uses thereof |
| KR102295963B1 (ko) * | 2020-03-05 | 2021-09-01 | 충북대학교 산학협력단 | 신규한 2-벤즈아미도옥사졸/티아졸 또는 2-페닐술폰아미도티아졸을 포함하는 하이드록삼산 화합물 및 이의 용도 |
| AU2021407396A1 (en) * | 2020-12-23 | 2023-07-13 | The University Of Queensland | Histone deacetylase inhibitors |
| EP4326263A1 (en) | 2021-04-23 | 2024-02-28 | Tenaya Therapeutics, Inc. | Hdac6 inhibitors for use in the treatment of dilated cardiomyopathy |
| TW202308619A (zh) | 2021-05-04 | 2023-03-01 | 美商特納亞治療股份有限公司 | 用於治療代謝疾病和hfpef的hdac6抑制劑 |
| CN117263936B (zh) * | 2023-11-21 | 2024-02-23 | 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 |
| WO2025215092A1 (en) | 2024-04-10 | 2025-10-16 | Institut National de la Santé et de la Recherche Médicale | Selective hdac6 inhibitors for use in the treatment of myotonic dystrophy type 1 |
| CN118515623B (zh) * | 2024-04-26 | 2025-04-25 | 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 |
Citations (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS511458A (enExample) * | 1974-05-28 | 1976-01-08 | Scherico Ltd | |
| JPS61151175A (ja) * | 1984-12-08 | 1986-07-09 | ヘキスト・アクチエンゲゼルシヤフト | 1‐フエニル‐イミダゾール‐5‐カルボン酸誘導体、それらの製造方法および植物成長調整剤としてのそれらの用途 |
| WO1989003818A1 (en) * | 1987-10-27 | 1989-05-05 | Warner-Lambert Company | Novel fenamic acid hydroxamate derivatives having cyclooxygenase and 5-lipoxygenase inhibition |
| JPH10500413A (ja) * | 1994-05-16 | 1998-01-13 | スミスクライン・ビーチャム・コーポレイション | 新規化合物 |
| WO2001023358A1 (en) * | 1999-09-27 | 2001-04-05 | Sagami Chemical Research Center | Pyrazole derivatives, intermediates for the preparation thereof, processes for the preparation of both and herbicides containing the derivatives as the active ingredient |
| WO2001052846A1 (en) * | 2000-01-18 | 2001-07-26 | Vertex Pharmaceuticals Incorporated | Gyrase inhibitors and uses thereof |
| JP2002510679A (ja) * | 1998-04-08 | 2002-04-09 | アボット・ラボラトリーズ | ピラゾールサイトカイン産生阻害剤 |
| JP2003520233A (ja) * | 2000-01-18 | 2003-07-02 | バーテックス ファーマシューティカルズ インコーポレイテッド | ジャイレースインヒビターおよびそれらの使用 |
| WO2005014588A1 (en) * | 2003-08-01 | 2005-02-17 | Argenta Discovery Limited | Substituted thienyl-hydroxamic acids having histone deacetylase activity |
| WO2005040161A1 (en) * | 2003-10-27 | 2005-05-06 | S*Bio Pte Ltd | Biaryl linked hydroxamates: preparation and pharmaceutical applications |
| JP2005534627A (ja) * | 2002-04-26 | 2005-11-17 | イーライ・リリー・アンド・カンパニー | タキキニン受容体アンタゴニスト |
| JP2005539001A (ja) * | 2002-08-02 | 2005-12-22 | アージェンタ・ディスカバリー・リミテッド | ヒストンデアセチラーゼインヒビターとしての置換チエニルヒドロキサム酸 |
| WO2006010749A2 (en) * | 2004-07-28 | 2006-02-02 | Janssen Pharmaceutica N.V. | Substituted propenyl piperazine derivatives as novel inhibitors of histone deacetylase |
| WO2006017214A2 (en) * | 2004-07-12 | 2006-02-16 | Merck & Co., Inc. | Inhibitors of histone deacetylase |
| JP2006511479A (ja) * | 2002-09-27 | 2006-04-06 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 3,4−二置換ピロールおよび炎症性疾患の治療におけるこれらの使用 |
| WO2006068933A2 (en) * | 2004-12-21 | 2006-06-29 | Merck & Co., Inc. | Mitotic kinesin inhibitors |
| JP2006516656A (ja) * | 2003-01-28 | 2006-07-06 | アヴェンティス ファーマ エス.エー. | N−アリールヘテロ芳香族物質、それを含む組成物およびその用途 |
| JP2006517960A (ja) * | 2003-02-18 | 2006-08-03 | ファイザー インコーポレイテッド | C型肝炎ウイルスの阻害剤、それを使用する組成物および治療法 |
| WO2006101454A1 (en) * | 2005-03-21 | 2006-09-28 | S*Bio Pte Ltd | Benzothiophene derivatives: preparation and pharmaceutical applications |
| WO2006123121A1 (en) * | 2005-05-19 | 2006-11-23 | Chroma Therapeutics Ltd | Histone deacetylase inhibitors |
| JP2007508318A (ja) * | 2003-10-09 | 2007-04-05 | エートン ファーマ インコーポレーティッド | チオフェンおよびベンゾチオフェンヒドロキサム酸誘導体 |
| WO2007070892A2 (en) * | 2005-12-16 | 2007-06-21 | Ironwood Pharmaceuticals, Inc. | Useful indole compounds |
| WO2007082880A1 (en) * | 2006-01-19 | 2007-07-26 | Janssen Pharmaceutica N.V. | Pyridine and pyrimidine derivatives as inhibitors of histone deacetylase |
| WO2007109178A2 (en) * | 2006-03-16 | 2007-09-27 | Pharmacyclics, Inc. | Indole derivatives as inhibitors of histone deacetylase |
| JP2007527914A (ja) * | 2004-03-08 | 2007-10-04 | ミイカナ セラピューティクス インコーポレイテッド | ヒストン脱アセチル化酵素の阻害剤 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2784925B2 (ja) * | 1988-09-07 | 1998-08-13 | 日本農薬株式会社 | 3又は5−フェニルピラゾール類又はその塩及び除草剤 |
| AU644281B2 (en) * | 1991-04-24 | 1993-12-02 | Sumitomo Pharmaceuticals Company, Limited | Novel thiazole derivatives |
| KR20070053362A (ko) * | 1999-11-23 | 2007-05-23 | 메틸진, 인크. | 히스톤 디아세틸라제의 억제제 |
| CA2469872A1 (en) * | 2001-12-12 | 2003-07-03 | F. Hoffmann-La Roche Ag | Benzothiophenes as adenosine receptor modulators |
| OA12792A (en) | 2002-03-13 | 2006-07-10 | Janssen Pharmaceutica Nv | Sulfonyl-derivatives as novel inhibitors of histone deacetylase. |
| BR0313160A (pt) | 2002-08-08 | 2005-07-12 | Smithkline Beecham Corp | Composto, composição farmacêutica, métodos para tratar uma condição e um neoplasmo suscetìvel em um animal em um animal, processo para preparar um composto e uso de um composto |
| SI1611112T1 (sl) * | 2003-02-11 | 2012-12-31 | Vernalis (R&D) Limited | Izoksazolne spojine kot inhibitorji vroäśinskih ĺ ok proteinov |
| US7094791B2 (en) * | 2003-07-31 | 2006-08-22 | Avalon Pharmaceuticals, Inc. | Derivatives of 3-hydroxy-pyrrole-2,4-dicarboxylic acid and uses thereof |
| EP1663953A1 (en) * | 2003-09-24 | 2006-06-07 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| KR101014328B1 (ko) * | 2004-04-27 | 2011-02-14 | 닛산 가가쿠 고교 가부시키 가이샤 | 피라졸술포닐우레아화합물 및 제초제 |
| CA2588633A1 (en) * | 2004-12-07 | 2006-06-15 | Toyama Chemical Co., Ltd. | Novel anthranilic acid derivative or salt thereof |
| MX2007011710A (es) | 2005-03-21 | 2007-11-20 | S Bio Pte Ltd | Derivados de imidazo[1,2-a]piridina, preparacion y aplicaciones farmaceuticas. |
| US20100218271A1 (en) | 2005-10-05 | 2010-08-26 | Crop Design N.V. | Plants having improved characteristics and method for making the same |
| CN101466670B (zh) * | 2006-04-07 | 2013-04-17 | 梅特希尔基因公司 | 组蛋白脱乙酰酶抑制剂 |
| CN105481788A (zh) * | 2006-10-28 | 2016-04-13 | 梅特希尔基因公司 | 组蛋白脱乙酰酶抑制剂 |
| US8030344B2 (en) * | 2007-03-13 | 2011-10-04 | Methylgene Inc. | Inhibitors of histone deacetylase |
| US20080234297A1 (en) * | 2007-03-20 | 2008-09-25 | Changgeng Qian | HSP90 Inhibitors Containing a Zinc Binding Moiety |
-
2008
- 2008-11-03 JP JP2010531384A patent/JP2011502133A/ja active Pending
- 2008-11-03 CN CN2008801238575A patent/CN101918389A/zh active Pending
- 2008-11-03 US US12/740,616 patent/US8673911B2/en active Active
- 2008-11-03 RU RU2010122304/04A patent/RU2501787C2/ru not_active IP Right Cessation
- 2008-11-03 WO PCT/CA2008/001911 patent/WO2009055917A1/en not_active Ceased
- 2008-11-03 BR BRPI0817897A patent/BRPI0817897A2/pt not_active IP Right Cessation
- 2008-11-03 EP EP08845130.7A patent/EP2217588A4/en not_active Withdrawn
- 2008-11-03 CA CA2703718A patent/CA2703718A1/en not_active Abandoned
- 2008-11-03 KR KR1020107012130A patent/KR20100095430A/ko not_active Ceased
-
2013
- 2013-03-14 US US13/829,403 patent/US20140045850A1/en not_active Abandoned
Patent Citations (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS511458A (enExample) * | 1974-05-28 | 1976-01-08 | Scherico Ltd | |
| JPS61151175A (ja) * | 1984-12-08 | 1986-07-09 | ヘキスト・アクチエンゲゼルシヤフト | 1‐フエニル‐イミダゾール‐5‐カルボン酸誘導体、それらの製造方法および植物成長調整剤としてのそれらの用途 |
| WO1989003818A1 (en) * | 1987-10-27 | 1989-05-05 | Warner-Lambert Company | Novel fenamic acid hydroxamate derivatives having cyclooxygenase and 5-lipoxygenase inhibition |
| JPH10500413A (ja) * | 1994-05-16 | 1998-01-13 | スミスクライン・ビーチャム・コーポレイション | 新規化合物 |
| JP2002510679A (ja) * | 1998-04-08 | 2002-04-09 | アボット・ラボラトリーズ | ピラゾールサイトカイン産生阻害剤 |
| WO2001023358A1 (en) * | 1999-09-27 | 2001-04-05 | Sagami Chemical Research Center | Pyrazole derivatives, intermediates for the preparation thereof, processes for the preparation of both and herbicides containing the derivatives as the active ingredient |
| WO2001052846A1 (en) * | 2000-01-18 | 2001-07-26 | Vertex Pharmaceuticals Incorporated | Gyrase inhibitors and uses thereof |
| JP2003520233A (ja) * | 2000-01-18 | 2003-07-02 | バーテックス ファーマシューティカルズ インコーポレイテッド | ジャイレースインヒビターおよびそれらの使用 |
| JP2005534627A (ja) * | 2002-04-26 | 2005-11-17 | イーライ・リリー・アンド・カンパニー | タキキニン受容体アンタゴニスト |
| JP2005539001A (ja) * | 2002-08-02 | 2005-12-22 | アージェンタ・ディスカバリー・リミテッド | ヒストンデアセチラーゼインヒビターとしての置換チエニルヒドロキサム酸 |
| JP2006511479A (ja) * | 2002-09-27 | 2006-04-06 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 3,4−二置換ピロールおよび炎症性疾患の治療におけるこれらの使用 |
| JP2006516656A (ja) * | 2003-01-28 | 2006-07-06 | アヴェンティス ファーマ エス.エー. | N−アリールヘテロ芳香族物質、それを含む組成物およびその用途 |
| JP2006517960A (ja) * | 2003-02-18 | 2006-08-03 | ファイザー インコーポレイテッド | C型肝炎ウイルスの阻害剤、それを使用する組成物および治療法 |
| WO2005014588A1 (en) * | 2003-08-01 | 2005-02-17 | Argenta Discovery Limited | Substituted thienyl-hydroxamic acids having histone deacetylase activity |
| JP2007508318A (ja) * | 2003-10-09 | 2007-04-05 | エートン ファーマ インコーポレーティッド | チオフェンおよびベンゾチオフェンヒドロキサム酸誘導体 |
| WO2005040161A1 (en) * | 2003-10-27 | 2005-05-06 | S*Bio Pte Ltd | Biaryl linked hydroxamates: preparation and pharmaceutical applications |
| JP2007527914A (ja) * | 2004-03-08 | 2007-10-04 | ミイカナ セラピューティクス インコーポレイテッド | ヒストン脱アセチル化酵素の阻害剤 |
| WO2006017214A2 (en) * | 2004-07-12 | 2006-02-16 | Merck & Co., Inc. | Inhibitors of histone deacetylase |
| WO2006010749A2 (en) * | 2004-07-28 | 2006-02-02 | Janssen Pharmaceutica N.V. | Substituted propenyl piperazine derivatives as novel inhibitors of histone deacetylase |
| WO2006068933A2 (en) * | 2004-12-21 | 2006-06-29 | Merck & Co., Inc. | Mitotic kinesin inhibitors |
| WO2006101454A1 (en) * | 2005-03-21 | 2006-09-28 | S*Bio Pte Ltd | Benzothiophene derivatives: preparation and pharmaceutical applications |
| WO2006123121A1 (en) * | 2005-05-19 | 2006-11-23 | Chroma Therapeutics Ltd | Histone deacetylase inhibitors |
| WO2007070892A2 (en) * | 2005-12-16 | 2007-06-21 | Ironwood Pharmaceuticals, Inc. | Useful indole compounds |
| WO2007082880A1 (en) * | 2006-01-19 | 2007-07-26 | Janssen Pharmaceutica N.V. | Pyridine and pyrimidine derivatives as inhibitors of histone deacetylase |
| WO2007109178A2 (en) * | 2006-03-16 | 2007-09-27 | Pharmacyclics, Inc. | Indole derivatives as inhibitors of histone deacetylase |
Non-Patent Citations (7)
| Title |
|---|
| JPN6014013744; Tetrahedron (2002), 58(42), 8581-8589 * |
| JPN6014013746; Journal of Organic Chemistry (1979), 44(4), 622-6 * |
| JPN6015008396; REGISTRY(STN)[online] , 1991 * |
| JPN6015008397; REGISTRY(STN)[online] , 1991 * |
| JPN7013002619; J.Chem.Soc.,Perkin.Trans.1,(1984),(10),p.2255-60 * |
| JPN7013002620; Organic Letters,(2006),8(8),p.1729-32 * |
| JPN7014001063; STN ON THE WEB, FILE REGISTRY, RN=949711-74-4,930745-00-9,889598-22-5,882222-60-8 * |
Cited By (14)
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| JP2016512512A (ja) * | 2013-03-14 | 2016-04-28 | シーエイチディーアイ ファウンデーション,インコーポレーテッド | ヒストンデアセチラーゼ阻害剤及びその組成物と使用方法 |
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| JP2018523663A (ja) * | 2015-08-04 | 2018-08-23 | チョン クン ダン ファーマシューティカル コーポレーション | ヒストン脱アセチル化酵素6阻害剤としての1,3,4−オキサジアゾール誘導体化合物及びこれを含有する薬剤学的組成物 |
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| US11958844B2 (en) | 2018-07-26 | 2024-04-16 | Chong Kun Dang Pharmaceutical Corp. | 1,3,4-oxadiazole derivative compounds as histone deacetylase 6 inhibitor, and pharmaceutical composition comprising the same |
| US12440484B2 (en) | 2019-05-31 | 2025-10-14 | Chong Kun Dang Pharmaceutical Corporation | 1,3,4-oxadiazole homophthalimide derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same |
| JP2023522058A (ja) * | 2020-04-17 | 2023-05-26 | 上海中澤医薬科技有限公司 | ベンゾナイトリック複素環式化合物及びその製造方法と使用 |
| JP7675101B2 (ja) | 2020-04-17 | 2025-05-12 | 上海中澤医薬科技有限公司 | ベンゾナイトリック複素環式化合物及びその製造方法と使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2008318244A1 (en) | 2009-05-07 |
| EP2217588A1 (en) | 2010-08-18 |
| EP2217588A4 (en) | 2013-12-04 |
| US20110021771A1 (en) | 2011-01-27 |
| CA2703718A1 (en) | 2009-05-07 |
| WO2009055917A1 (en) | 2009-05-07 |
| CN101918389A (zh) | 2010-12-15 |
| RU2010122304A (ru) | 2011-12-10 |
| RU2501787C2 (ru) | 2013-12-20 |
| US8673911B2 (en) | 2014-03-18 |
| BRPI0817897A2 (pt) | 2019-09-24 |
| KR20100095430A (ko) | 2010-08-30 |
| US20140045850A1 (en) | 2014-02-13 |
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