TWI694073B - 作為組蛋白去乙醯酶６抑制劑之二唑胺衍生物及含彼之醫藥組合物 - Google Patents

作為組蛋白去乙醯酶６抑制劑之二唑胺衍生物及含彼之醫藥組合物 Download PDF

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Publication number: TWI694073B
Authority: TW; Taiwan
Prior art keywords: amine; diazol; cyclobutyl; pyrimidine; difluoromethyl
Prior art date: 2015-10-12

Application number

TW105132939A

Other languages

English (en)

Chinese (zh)

Other versions

TW201716397A (zh

Inventor

金潤泰

李昌埴

吳正澤

宋彗丞

崔眞

李在英

Original Assignee

韓商鐘根堂股份有限公司

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

2015-10-12

Filing date

2016-10-12

Publication date

2020-05-21

2016-10-12 Application filed by 韓商鐘根堂股份有限公司 filed Critical 韓商鐘根堂股份有限公司

2017-05-16 Publication of TW201716397A publication Critical patent/TW201716397A/zh

2020-05-21 Application granted granted Critical

2020-05-21 Publication of TWI694073B publication Critical patent/TWI694073B/zh

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239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 13
108010023925 Histone Deacetylase 6 Proteins 0.000 title abstract description 34
102000011427 Histone Deacetylase 6 Human genes 0.000 title abstract 4
239000003112 inhibitor Substances 0.000 title description 2
COXRPBBNPBCNDM-UHFFFAOYSA-N Dioxamide Natural products C1=C2OCOC2=CC(C=CC(=O)N(CCC=2C=C3OCOC3=CC=2)C)=C1 COXRPBBNPBCNDM-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 246
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 41
201000010099 disease Diseases 0.000 claims abstract description 37
150000003839 salts Chemical class 0.000 claims abstract description 36
102000003964 Histone deacetylase Human genes 0.000 claims abstract description 20
108090000353 Histone deacetylase Proteins 0.000 claims abstract description 20
206010028980 Neoplasm Diseases 0.000 claims abstract description 13
238000002360 preparation method Methods 0.000 claims abstract description 12
208000012902 Nervous system disease Diseases 0.000 claims abstract description 6
208000025966 Neurological disease Diseases 0.000 claims abstract description 6
208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 4
206010008805 Chromosomal abnormalities Diseases 0.000 claims abstract description 4
208000031404 Chromosome Aberrations Diseases 0.000 claims abstract description 4
208000035473 Communicable disease Diseases 0.000 claims abstract description 4
206010010356 Congenital anomaly Diseases 0.000 claims abstract description 4
230000003542 behavioural effect Effects 0.000 claims abstract description 4
208000010643 digestive system disease Diseases 0.000 claims abstract description 4
208000016097 disease of metabolism Diseases 0.000 claims abstract description 4
230000002124 endocrine Effects 0.000 claims abstract description 4
208000030172 endocrine system disease Diseases 0.000 claims abstract description 4
230000036244 malformation Effects 0.000 claims abstract description 4
230000001404 mediated effect Effects 0.000 claims abstract description 4
230000003340 mental effect Effects 0.000 claims abstract description 4
210000002346 musculoskeletal system Anatomy 0.000 claims abstract description 4
208000023504 respiratory system disease Diseases 0.000 claims abstract description 4
LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims description 223
-1 Diazolamide derivative compounds Chemical class 0.000 claims description 51
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 20
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 17
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 15
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 14
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
125000004122 cyclic group Chemical group 0.000 claims description 11
125000000753 cycloalkyl group Chemical group 0.000 claims description 10
125000002757 morpholinyl group Chemical group 0.000 claims description 9
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 6
102000004190 Enzymes Human genes 0.000 claims description 6
108090000790 Enzymes Proteins 0.000 claims description 6
229930192474 thiophene Natural products 0.000 claims description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 5
125000003118 aryl group Chemical group 0.000 claims description 5
125000001072 heteroaryl group Chemical group 0.000 claims description 5
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 4
208000019498 Skin and subcutaneous tissue disease Diseases 0.000 claims description 3
208000018631 connective tissue disease Diseases 0.000 claims description 3
208000035475 disorder Diseases 0.000 claims description 3
208000017445 musculoskeletal system disease Diseases 0.000 claims description 3
229910052757 nitrogen Inorganic materials 0.000 claims description 3
208000017520 skin disease Diseases 0.000 claims description 3
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 claims description 2
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
239000000203 mixture Substances 0.000 abstract description 80
238000000034 method Methods 0.000 abstract description 26
230000002401 inhibitory effect Effects 0.000 abstract description 13
239000003814 drug Substances 0.000 abstract description 11
210000002808 connective tissue Anatomy 0.000 abstract 1
206010033675 panniculitis Diseases 0.000 abstract 1
230000002265 prevention Effects 0.000 abstract 1
210000004304 subcutaneous tissue Anatomy 0.000 abstract 1
230000001225 therapeutic effect Effects 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 801
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 511
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 414
239000000243 solution Substances 0.000 description 362
239000011541 reaction mixture Substances 0.000 description 303
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 274
235000019439 ethyl acetate Nutrition 0.000 description 267
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 253
239000007787 solid Substances 0.000 description 237
239000012044 organic layer Substances 0.000 description 207
238000000605 extraction Methods 0.000 description 203
239000012141 concentrate Substances 0.000 description 184
229920006395 saturated elastomer Polymers 0.000 description 178
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 168
229910004298 SiO 2 Inorganic materials 0.000 description 143
238000004440 column chromatography Methods 0.000 description 139
239000011780 sodium chloride Substances 0.000 description 137
238000006243 chemical reaction Methods 0.000 description 134
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 133
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 123
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 123
YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 115
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 111
239000002904 solvent Substances 0.000 description 98
230000002829 reductive effect Effects 0.000 description 97
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 81
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 72
239000010410 layer Substances 0.000 description 71
239000012455 biphasic mixture Substances 0.000 description 70
229920003023 plastic Polymers 0.000 description 70
239000004033 plastic Substances 0.000 description 70
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 69
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 61
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 61
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 61
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 58
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 56
238000000746 purification Methods 0.000 description 53
150000001335 aliphatic alkanes Chemical class 0.000 description 49
238000001914 filtration Methods 0.000 description 48
239000002244 precipitate Substances 0.000 description 48
238000003756 stirring Methods 0.000 description 40
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 38
239000002253 acid Substances 0.000 description 35
229910000030 sodium bicarbonate Inorganic materials 0.000 description 35
235000017557 sodium bicarbonate Nutrition 0.000 description 35
IYXUFOCLMOXQSL-UHFFFAOYSA-N (2,2-difluoroacetyl) 2,2-difluoroacetate Chemical compound FC(F)C(=O)OC(=O)C(F)F IYXUFOCLMOXQSL-UHFFFAOYSA-N 0.000 description 33
239000012230 colorless oil Substances 0.000 description 32
102100022537 Histone deacetylase 6 Human genes 0.000 description 30
IEMKQRSOAOPKRJ-UHFFFAOYSA-N ethyl 2-chloropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)N=C1 IEMKQRSOAOPKRJ-UHFFFAOYSA-N 0.000 description 30
239000005708 Sodium hypochlorite Substances 0.000 description 24
239000012043 crude product Substances 0.000 description 24
SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 24
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 23
239000012312 sodium hydride Substances 0.000 description 23
229910000104 sodium hydride Inorganic materials 0.000 description 23
230000000694 effects Effects 0.000 description 22
VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 20
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 19
239000007864 aqueous solution Substances 0.000 description 16
OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 16
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 11
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
JQCSUVJDBHJKNG-UHFFFAOYSA-N 1-methoxy-ethyl Chemical group C[CH]OC JQCSUVJDBHJKNG-UHFFFAOYSA-N 0.000 description 8
201000011510 cancer Diseases 0.000 description 8
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 8
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 8
239000003276 histone deacetylase inhibitor Substances 0.000 description 7
238000006467 substitution reaction Methods 0.000 description 7
NQIXZNWSYYGSCI-UHFFFAOYSA-N 1-[3-(trifluoromethyl)phenyl]cyclobutan-1-amine;hydrochloride Chemical compound Cl.C=1C=CC(C(F)(F)F)=CC=1C1(N)CCC1 NQIXZNWSYYGSCI-UHFFFAOYSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
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KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
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SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 6
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HFGPILYXODGBHF-UHFFFAOYSA-N ethyl 2-[[1-[3-(trifluoromethyl)phenyl]cyclobutyl]amino]pyrimidine-5-carboxylate Chemical compound FC(C=1C=C(C=CC=1)C1(CCC1)NC1=NC=C(C=N1)C(=O)OCC)(F)F HFGPILYXODGBHF-UHFFFAOYSA-N 0.000 description 5
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ODWPTXHRLRYUEW-UHFFFAOYSA-N 1-phenylcyclopentan-1-amine;hydrochloride Chemical compound Cl.C=1C=CC=CC=1C1(N)CCCC1 ODWPTXHRLRYUEW-UHFFFAOYSA-N 0.000 description 4
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239000001257 hydrogen Substances 0.000 description 4
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125000006239 protecting group Chemical group 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 4
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- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/33—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/33—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C211/34—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton
- C07C211/35—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton containing only non-condensed rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
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General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
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Chemical Kinetics & Catalysis (AREA)
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Diabetes (AREA)
Orthopedic Medicine & Surgery (AREA)
Cardiology (AREA)
Physical Education & Sports Medicine (AREA)
Ophthalmology & Optometry (AREA)
Neurosurgery (AREA)
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Pulmonology (AREA)
Biomedical Technology (AREA)
Heart & Thoracic Surgery (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Hematology (AREA)
Obesity (AREA)
Endocrinology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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TW105132939A 2015-10-12 2016-10-12 作為組蛋白去乙醯酶６抑制劑之二唑胺衍生物及含彼之醫藥組合物 TWI694073B (zh)

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KR10-2015-0142014		2015-10-12

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US (1)	US10494355B2 (2)
EP (1)	EP3362445B1 (2)
JP (1)	JP6697074B2 (2)
KR (1)	KR101839137B1 (2)
CN (1)	CN108699048B (2)
AU (1)	AU2016338118B2 (2)
CA (1)	CA3001666C (2)
DK (1)	DK3362445T3 (2)
ES (1)	ES2940413T3 (2)
FI (1)	FI3362445T3 (2)
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Families Citing this family (37)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PL3292116T3 (pl)	2015-02-02	2022-02-21	Valo Health, Inc.	3-arylo-4-amidobicykliczne kwasy [4,5,0]hydroksamowe jako inhibitory hdac
TW201636329A (zh)	2015-02-02	2016-10-16	佛瑪治療公司	作為ｈｄａｃ抑制劑之雙環［４，６，０］異羥肟酸
CN108026056B (zh)	2015-07-27	2021-08-03	株式会社钟根堂	作为组蛋白脱乙酰酶6抑制剂的1,3,4-噁二唑酰胺衍生物化合物及其药物组合物
RU2695227C9 (ru)	2015-07-27	2020-03-04	Чонг Кун Данг Фармасьютикал Корп.	Производные 1,3,4-оксадиазолсульфамида в качестве ингибитора гистондеацетилазы 6 и содержащая их фармацевтическая композиция
PL3328843T3 (pl)	2015-07-27	2023-02-27	Chong Kun Dang Pharmaceutical Corp.	Związki będące pochodnymi 1,3,4 oksadiazolosulfonamidów jako inhibitor deacetylazy histonowej 6, oraz kompozycja farmaceutyczna je zawierająca
JP6491393B2 (ja)	2015-08-04	2019-03-27	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
JP6697074B2 (ja)	2015-10-12	2020-05-20	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阻害剤としてのオキサジアゾールアミン誘導体化合物及びこれを含有する薬剤学的組成物
EP3472131B1 (en)	2016-06-17	2020-02-19	Forma Therapeutics, Inc.	2-spiro-5- and 6-hydroxamic acid indanes as hdac inhibitors
WO2018165520A1 (en)	2017-03-10	2018-09-13	Vps-3, Inc.	Metalloenzyme inhibitor compounds
KR102316234B1 (ko)	2018-07-26	2021-10-22	주식회사 종근당	히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 유도체 화합물 및 이를 포함하는 약제학적 조성물
PY19106549A (es)	2018-12-21	2021-07-13	Bayer Ag	1,3,4-oxadiazoles y derivados de éstos como nuevos agentes fungicidas
US12084436B2 (en)	2019-01-30	2024-09-10	Takeda Pharmaceutical Company Limited	Heterocyclic compound
CN111848423B (zh) *	2019-04-30	2022-10-14	尚科生物医药（上海）有限公司	3-氧代环丁基氨基甲酸叔丁酯的制备方法
MY207444A (en)	2019-05-31	2025-02-27	Chong Kun Dang Pharmaceutical Corp	1,3,4-oxadiazole homophthalimide derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same
JP2022538284A (ja)	2019-06-27	2022-09-01	ザジョージワシントンユニバーシティ，アコングレッショナリーチャータードノット－フォー－プロフィットコーポレイション	Ｈｄａｃ６活性化マクロファージ、その組成物および使用
AU2020321955A1 (en)	2019-07-30	2022-03-17	Eikonizo Therapapeutics, Inc.	HDAC6 inhibitors and uses thereof
WO2021060567A1 (en)	2019-09-27	2021-04-01	Takeda Pharmaceutical Company Limited	2-isoindol-1,3,4-oxadiazole derivatives useful as hdac6 inhibitors
MX2022007376A (es) *	2019-12-20	2022-09-02	Tenaya Therapeutics Inc	Fluoroalqull-oxadiazoles y sus usos.
US11339150B2 (en)	2019-12-27	2022-05-24	Onkure, Inc.	Benzimidazole compounds as HDAC6 inhibitors
WO2021255089A1 (en)	2020-06-19	2021-12-23	Bayer Aktiengesellschaft	1,3,4-oxadiazole pyrimidines and 1,3,4-oxadiazole pyridines as fungicides
WO2021255091A1 (en)	2020-06-19	2021-12-23	Bayer Aktiengesellschaft	1,3,4-oxadiazoles and their derivatives as fungicides
UY39276A (es)	2020-06-19	2022-01-31	Bayer Ag	Uso de compuestos de 1,3,4–oxadiazol–2–ilpirimidina para controlar microorganismos fitopatógenos, métodos de uso y composiciones.
WO2021255093A1 (en)	2020-06-19	2021-12-23	Bayer Aktiengesellschaft	Active compound combination
UY39275A (es)	2020-06-19	2022-01-31	Bayer Ag	1,3,4-oxadiazol pirimidinas como fungicidas, procesos e intermediarios para su preparación, métodos de uso y usos de los mismos
KR20230049675A (ko)	2020-08-07	2023-04-13	이탈파마코 에스.피.에이.	신규한 옥사디아졸-기반 선택적 hdac6 억제제
EP4308097A4 (en) *	2021-03-15	2025-08-20	Univ Michigan Regents	NON-HYDROXAMATE HDAC6 INHIBITORS AND METHODS OF USE THEREOF
IL307883A (en)	2021-04-23	2023-12-01	Tenaya Therapeutics Inc	HDAC6 inhibitors for use in the treatment of dilated myocardial disease
US20240252502A1 (en)	2021-05-04	2024-08-01	Tenaya Therapeutics, Inc.	Hdac6 inhibitors for treatment of metabolic disease and hfpef
AU2022291768A1 (en)	2021-06-16	2023-11-30	Celgene Corporation	Azetidinyl compounds comprising a carboxylic acid group for the treatment of neurodegenerative diseases
CN115572244B (zh) *	2021-06-21	2024-04-30	复旦大学	2’-芳基查尔酮类化合物及其制备方法和在制药中的用途
US20250263405A1 (en) *	2021-11-04	2025-08-21	Valo Health, Inc.	Histone deacetylase 6 inhibitor compounds and uses thereof
TW202345813A (zh)	2022-04-08	2023-12-01	美商艾科尼佐療法股份有限公司	㗁二唑ｈｄａｃ６抑制劑及其用途
CA3262628A1 (en) *	2022-08-08	2024-02-15	Italfarmaco S.P.A.	HYDRAZIDES DIFLOORO- AND TRIFLUORO-ACETYLE USED AS SELECTIVE HDAC6 INHIBITORS
CN115286615A (zh) *	2022-09-01	2022-11-04	深圳市真味生物科技有限公司	一种消旋尼古丁的制备方法
CN117986146A (zh) *	2023-12-22	2024-05-07	河南优凯制药有限公司	一种枸橼酸喷托维林杂质的制备方法及其检测方法
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
US20260109690A1 (en) *	2024-05-31	2026-04-23	Baerenkraft Therapeutics, Llc.	Hdac6 inhibitors and method of their use

Citations (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20130059883A1 (en) *	2010-01-13	2013-03-07	Tempero Pharmaceuticals, Inc.	Compounds and methods
WO2013066833A1 (en) *	2011-10-31	2013-05-10	Glaxosmithkline Llc	Compounds and methods to inhibit histone deacetylase (hdac) enzymes
US20140142105A1 (en) *	2011-07-08	2014-05-22	Novartis Ag	Novel trifluoromethyl-oxadiazole derivatives and their use in the treatment of disease
US8981084B2 (en) *	2010-01-13	2015-03-17	Tempero Pharmaceuticals, Inc.	Oxadiazole HDAC inhibitors
US20170015809A1 (en) *	2015-07-14	2017-01-19	Rohm And Haas Company	Process for preparing hydrophobically modified alkylene oxide urethane polymer

Family Cites Families (43)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0276432A3 (de)	1986-12-12	1988-10-26	Ciba-Geigy Ag	Schädlingsbekämpfungsmittel
KR100265385B1 (ko)	1998-02-27	2000-11-01	윤여표	순환기 질환의 예방 및 치료 효능을 갖는 홍경천 추출물
US7868204B2 (en)	2001-09-14	2011-01-11	Methylgene Inc.	Inhibitors of histone deacetylase
US6897220B2 (en)	2001-09-14	2005-05-24	Methylgene, Inc.	Inhibitors of histone deacetylase
JP2005509606A (ja)	2001-10-03	2005-04-14	ファルマシア・コーポレーション	凝血カスケードを選択的に阻害するのに有用な置換された多環式化合物のプロドラッグ
CA2471099C (en)	2001-12-20	2011-04-12	Bristol-Myers Squibb Company	.alpha.-(n-sulphonamido)acetamide derivatives as .beta.-amyloid inhibitors
EA200800321A1 (ru)	2005-07-14	2008-06-30	Такеда Сан Диего, Инк.	Ингибиторы гистондеацетилазы
DK1910384T3 (da)	2005-08-04	2012-12-17	Sirtris Pharmaceuticals Inc	Imidazo [2,1-b] thiazol-derivater som sirtuinmodulerende forbindelser
WO2007032445A1 (ja)	2005-09-16	2007-03-22	Kyowa Hakko Kogyo Co., Ltd.	タンパク質キナーゼ阻害剤
WO2007107758A1 (en)	2006-03-23	2007-09-27	Prolysis Ltd	Antibacterial agents
TW200808707A (en)	2006-06-14	2008-02-16	Methylgene Inc	Sulfamide and sulfamate derivatives as histone deacetylase inhibitors
EP1878730A1 (en)	2006-07-12	2008-01-16	Bayer Schering Pharma Aktiengesellschaft	Substituted isoxazolines, pharmaceutical compositions containing the same, methods of preparing the same, and uses of the same
CA2670707A1 (en)	2006-12-11	2008-06-19	Genentech, Inc.	Compositions and methods for treating a neoplasm
JP5478488B2 (ja)	2007-06-20	2014-04-23	メルク・シャープ・アンド・ドーム・コーポレーション	Ｊａｎｕｓキナーゼの阻害剤
WO2009010479A2 (en)	2007-07-13	2009-01-22	Euroscreen S.A.	Heterocyclic methylene piperidine derivatives and their use
KR100903743B1 (ko)	2007-08-28	2009-06-19	전병태	소화기계 질환개선 및 예방용 식품 조성물
JP5611826B2 (ja)	2007-09-04	2014-10-22	ザスクリプスリサーチインスティテュート	タンパク質キナーゼ阻害剤としての置換されたピリミジニル−アミン
AU2008318343B2 (en)	2007-11-02	2013-07-18	Dilafor Ab	Non-anticoagulant polysaccharide compositions
CN101918389A (zh)	2007-11-02	2010-12-15	梅特希尔基因公司	组蛋白脱乙酰酶抑制剂
AU2009274549B2 (en)	2008-07-23	2014-05-01	Dana-Farber Cancer Institute, Inc.	Deacetylase inhibitors and uses thereof
WO2010123933A1 (en)	2009-04-20	2010-10-28	Institute For Oneworld Health	Compounds, compositions and methods comprising 1,3,4-oxadiazole derivatives
WO2010126002A1 (ja)	2009-04-28	2010-11-04	塩野義製薬株式会社	ヘテロ環スルホンアミド化合物を含有する医薬
JP2011008205A (ja)	2009-05-27	2011-01-13	Fujifilm Corp	二軸性光学異方性膜を作製するための組成物
BR112012021476A2 (pt)	2010-02-25	2019-09-24	Piramal Entpr Ltd	composto, processo para preparação do composto, composição farmacêutica compreendendo uma quantidade terapeuticamente eficaz do composto e emprego de tal composto
AR081331A1 (es) *	2010-04-23	2012-08-08	Cytokinetics Inc	Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos
NZ603477A (en) *	2010-05-12	2014-09-26	Vertex Pharma	Compounds useful as inhibitors of atr kinase
US8697739B2 (en)	2010-07-29	2014-04-15	Novartis Ag	Bicyclic acetyl-CoA carboxylase inhibitors and uses thereof
PT2673285T (pt)	2010-12-09	2017-10-19	Wockhardt Ltd	Resumo
KR101262870B1 (ko)	2011-01-28	2013-05-09	환인제약 주식회사	호장근 추출물을 함유하는 호흡기 질환의 예방 또는 치료용 조성물
EP2734500A4 (en)	2011-07-20	2015-04-08	Gen Hospital Corp	SELECTIVE HISTONDEACETYLASE-6 INHIBITORS FOR THE TREATMENT OF BONE DISORDERS
WO2013066835A2 (en)	2011-10-31	2013-05-10	Glaxosmithkline Llc	Compounds and methods
WO2013066839A2 (en) *	2011-10-31	2013-05-10	Glaxosmithkline Llc	Compounds and methods
BR112014012815A8 (pt) *	2011-11-28	2017-06-20	Novartis Ag	derivados de trifluormetil-oxadiazol e uso dos mesmos no tratamento de doença
WO2013078544A1 (en)	2011-11-29	2013-06-06	Beta Pharma Canada Inc.	Heterocyclic amides compounds which are hdac6 inhibitors and used as anti-tumoral agents
EA029661B1 (ru)	2013-09-06	2018-04-30	Ауриген Дискавери Текнолоджиз Лимитед	Производные 1,3,4-оксадиазола и 1,3,4-тиадиазола в качестве иммуномодуляторов
US9650379B2 (en)	2013-12-12	2017-05-16	Chong Kun Dang Pharmaceutical Corp.	Azaindole derivatives as selective histone deacetylase (HDAC) inhibitors and pharmaceutical compositions comprising the same
CN104744446B (zh) *	2013-12-30	2019-06-25	广东东阳光药业有限公司	杂芳化合物及其在药物中的应用
ES2713700T3 (es)	2014-11-24	2019-05-23	Medifron Dbt Inc	Derivados de carboxamida y urea a base de oxazol y tiazol sustituidos como ligandos del receptor de vainilloide II
RU2695227C9 (ru)	2015-07-27	2020-03-04	Чонг Кун Данг Фармасьютикал Корп.	Производные 1,3,4-оксадиазолсульфамида в качестве ингибитора гистондеацетилазы 6 и содержащая их фармацевтическая композиция
CN108026056B (zh)	2015-07-27	2021-08-03	株式会社钟根堂	作为组蛋白脱乙酰酶6抑制剂的1,3,4-噁二唑酰胺衍生物化合物及其药物组合物
PL3328843T3 (pl)	2015-07-27	2023-02-27	Chong Kun Dang Pharmaceutical Corp.	Związki będące pochodnymi 1,3,4 oksadiazolosulfonamidów jako inhibitor deacetylazy histonowej 6, oraz kompozycja farmaceutyczna je zawierająca
JP6491393B2 (ja) *	2015-08-04	2019-03-27	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
JP6697074B2 (ja)	2015-10-12	2020-05-20	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阻害剤としてのオキサジアゾールアミン誘導体化合物及びこれを含有する薬剤学的組成物

2016
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- 2018-04-10 PH PH12018500773A patent/PH12018500773A1/en unknown

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20130059883A1 (en) *	2010-01-13	2013-03-07	Tempero Pharmaceuticals, Inc.	Compounds and methods
US8981084B2 (en) *	2010-01-13	2015-03-17	Tempero Pharmaceuticals, Inc.	Oxadiazole HDAC inhibitors
US20140142105A1 (en) *	2011-07-08	2014-05-22	Novartis Ag	Novel trifluoromethyl-oxadiazole derivatives and their use in the treatment of disease
WO2013066833A1 (en) *	2011-10-31	2013-05-10	Glaxosmithkline Llc	Compounds and methods to inhibit histone deacetylase (hdac) enzymes
US20170015809A1 (en) *	2015-07-14	2017-01-19	Rohm And Haas Company	Process for preparing hydrophobically modified alkylene oxide urethane polymer

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HRP20230201T1 (hr)	2023-03-31
CA3001666A1 (en)	2017-04-20
AU2016338118A1 (en)	2018-04-12
US10494355B2 (en)	2019-12-03
PT3362445T (pt)	2023-03-20
PH12018500773B1 (en)	2018-10-29
PL3362445T3 (pl)	2023-08-07
PH12018500773A1 (en)	2018-10-29
MY196174A (en)	2023-03-20
TW201716397A (zh)	2017-05-16
EP3362445B1 (en)	2023-01-25
US20180273495A1 (en)	2018-09-27
KR20170043091A (ko)	2017-04-20
HUE061967T2 (hu)	2023-09-28
EP3362445A1 (en)	2018-08-22
CN108699048B (zh)	2021-12-28
NZ740809A (en)	2019-04-26
KR101839137B1 (ko)	2018-03-26
ES2940413T3 (es)	2023-05-08
RU2695133C1 (ru)	2019-07-22
JP2018530571A (ja)	2018-10-18
JP6697074B2 (ja)	2020-05-20
CA3001666C (en)	2021-03-30
DK3362445T3 (da)	2023-02-27
BR112018007289A2 (pt)	2018-10-23
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Publication	Publication Date	Title
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TWI639587B (zh)	2018-11-01	作為組蛋白去乙醯酶６抑制劑之１，３，４－二唑磺胺衍生物及含彼之醫藥組合物
CN106232584A (zh)	2016-12-14	作为组蛋白脱乙酰酶6抑制剂的新型化合物和包含其的药物组合物
CN108026056B (zh)	2021-08-03	作为组蛋白脱乙酰酶6抑制剂的1,3,4-噁二唑酰胺衍生物化合物及其药物组合物
TW201632497A (zh)	2016-09-16	３－側氧基－３－（芳基胺基）丙酸脂，其製備程序，及其於製備吡咯酮的應用
CN104822653B (zh)	2017-03-08	N‑丙‑2‑炔基甲酰胺衍生物及其作为trpa1拮抗剂的用途
TWI617545B (zh)	2018-03-11	作為選擇性組織蛋白去乙醯酶抑制劑之雜環烷基衍生物化合物及包含其之醫藥組合物
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CN110267963A (zh)	2019-09-20	Magl抑制剂
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