KR20200097294A - 히스톤 디아세틸라제 6 억제제로서의 1,2,4-옥사디아졸 유도체 - Google Patents
히스톤 디아세틸라제 6 억제제로서의 1,2,4-옥사디아졸 유도체 Download PDFInfo
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- KR20200097294A KR20200097294A KR1020207019402A KR20207019402A KR20200097294A KR 20200097294 A KR20200097294 A KR 20200097294A KR 1020207019402 A KR1020207019402 A KR 1020207019402A KR 20207019402 A KR20207019402 A KR 20207019402A KR 20200097294 A KR20200097294 A KR 20200097294A
- Authority
- KR
- South Korea
- Prior art keywords
- pyridin
- trifluoromethyl
- compound
- oxadiazol
- oxadiazole
- 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.)
- Granted
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- 239000003112 inhibitor Substances 0.000 title claims abstract description 32
- 108010023925 Histone Deacetylase 6 Proteins 0.000 title abstract description 102
- 102000011427 Histone Deacetylase 6 Human genes 0.000 title abstract 3
- 150000005071 1,2,4-oxadiazoles Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 410
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims description 168
- 102100022537 Histone deacetylase 6 Human genes 0.000 claims description 105
- 150000003839 salts Chemical class 0.000 claims description 97
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 89
- 201000010099 disease Diseases 0.000 claims description 58
- 125000000217 alkyl group Chemical group 0.000 claims description 56
- 125000000623 heterocyclic group Chemical group 0.000 claims description 52
- -1 propane Amide Chemical class 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 41
- 125000001072 heteroaryl group Chemical group 0.000 claims description 36
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 33
- 208000035475 disorder Diseases 0.000 claims description 31
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 25
- 206010028980 Neoplasm Diseases 0.000 claims description 24
- 125000006413 ring segment Chemical group 0.000 claims description 23
- 229920006395 saturated elastomer Polymers 0.000 claims description 23
- 201000011510 cancer Diseases 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 21
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 19
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- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 11
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 8
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- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 7
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- 238000004519 manufacturing process Methods 0.000 claims description 6
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 4
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- GWXDARYYTLNCMG-UHFFFAOYSA-N tert-butyl N-(6-bromopyridin-3-yl)-N-[3-(4,4-difluoropiperidin-1-yl)propyl]carbamate Chemical compound BrC1=CC=C(C=N1)N(C(OC(C)(C)C)=O)CCCN1CCC(CC1)(F)F GWXDARYYTLNCMG-UHFFFAOYSA-N 0.000 description 1
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- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- FERKWUXUTFCIFW-UHFFFAOYSA-N trimethyl-[2-[[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]methoxy]ethyl]silane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN(COCC[Si](C)(C)C)N=C1 FERKWUXUTFCIFW-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LYRCQNDYYRPFMF-UHFFFAOYSA-N trimethyltin Chemical class C[Sn](C)C LYRCQNDYYRPFMF-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Oncology (AREA)
- Neurosurgery (AREA)
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- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
Claims (31)
- 화학식 (I)의 화합물 또는 이의 염:
여기서
m은 0, 1 또는 2이고;
각각의 R1은 독립적으로 할로, 메틸 및 트리플루오로메틸로부터 선택되며;
A는
i) 전 방향족(fully aromatic)인 5- 또는 6-원 모노사이클릭 또는 9- 또는 10-원 바이사이클릭 헤테로아릴 고리, 및
ii) 포화 또는 부분 불포화된 카보사이클릭 또는 헤테로사이클릭 고리에 융합된 5- 또는 6-원 모노사이클릭 헤테로아릴 고리로 이루어진 9- 또는 10-원 바이사이클릭 헤테로아릴 고리로부터 선택되고: 상기 9- 또는 10-원 바이사이클릭 헤테로사이클릭 고리는 5- 또는 6-원 모노사이클릭 헤테로아릴 고리를 통해 분자의 잔기(rest)에 연결되며,
상기 A는 고리 A가 분자의 잔기에 부착되는 고리 원자에 인접한 위치에 하나의 고리 N 원자를 포함하고, 상기 A는 독립적으로 N, 0 및 S로부터 선택된 1개 내지 3개의 추가 고리 헤테로원자를 임의로 포함하며,
상기 A는 1개 또는 2개의 R2로 임의로 치환되고, 추가로 A는 하나의 R3으로 임의로 치환되며,
각각의 R2는 독립적으로 할로, C1-6 알킬, C1-6 할로알킬, C3-7 사이클로알킬 및 -(C1-6 알킬렌)-OR4로부터 선택되고;
R3은 -L1-R5, -L2-OR6, -L3-NR7R8, -L4-CONR9R10, -L5-NR11COR12, -Y-L6-OR6 및 -Y-L7-NR7R8로부터 선택되며;
L1, L2, L3, L4 및 L5는 각각 독립적으로 결합 및 C1-6 알킬렌으로부터 선택되고;
L6 및 L7은 각각 독립적으로 C2-6 알킬렌으로부터 선택되며;
각각의 Y는 독립적으로 -O-, -NR13-, -CONR14- 및 -NR15CO-로부터 선택되고;
각각의 R4는 독립적으로 수소, C1-6 알킬, C1-6 할로알킬, C3-7 사이클로알킬 및 C3-7 사이클로알킬-C1-6 알킬로부터 선택되며;
각각의 R5는 독립적으로 카보사이클릴, 아릴, 헤테로사이클릴 및 헤테로아릴로부터 선택되고, 상기 카보사이클릴, 아릴, 헤테로사이클릴 및 헤테로아릴은 각각 하나 이상의 R16으로 임의로 치환되며;
R6 및 R12는 각각 독립적으로 수소, C1-6 알킬, C1-6 할로알킬 및 -L1-R5로부터 선택되고;
R7 및 R8은 각각 독립적으로 수소, C1-6 알킬, C1-6 할로알킬, -(C1-6 알킬렌) -OR4 및 -L1-R5로부터 선택되며;
R9 및 R10은 각각 독립적으로 수소, C1-6 알킬, C1-6 할로알킬, -(C1-6 알킬렌) -OR4 및 -L1-R5로부터 선택되거나, 또는 R9 및 R10은 이들이 부착된 N 원자와 함께 N, O 및 S로부터 선택된 하나의 추가 헤테로원자를 임의로 포함하는 포화된 4- 내지 12-원 헤테로사이클릭 고리를 형성하고, 상기 헤테로사이클릭 고리는 하나 이상의 R16으로 임의로 치환되며;
R11, R13, R14 및 R15는 각각 독립적으로 수소, C1-6 알킬, C1-6 할로알킬, C3-7 사이클로알킬, C3-7 사이클로알킬-C1-6 알킬 및 -(C1-6 알킬렌) -OR4로부터 선택되고;
각각의 R16은 독립적으로 C1-6 알킬, C1-6 할로알킬, 할로, C1-6 알콕시, C1-6 할로알콕시, -OH, -NR17R18, -COR19, -CN, -L8-카보사이클릴, -L8-아릴, -L8-헤테로사이클릴 및 -L8-헤테로아릴로부터 선택되며, 상기 -L8-카보사이클릴 내의 카보사이클릴, -L8-아릴 내의 아릴, -L8-헤테로사이클릴 내의 헤테로사이클릴 및 -L8-헤테로아릴 내의 헤테로아릴은 각각 하나 이상의 R20으로 임의로 치환되고;
각각의 L8은 독립적으로 결합 및 C1-6 알킬렌으로부터 선택되며;
R17 및 R18은 각각 독립적으로 수소, C1-6 알킬, C1-6 할로알킬, C3-7 사이클로알킬 및 C3-7 사이클로알킬-C1-6 알킬로부터 선택되고;
R19는 수소, C1-6 알킬 및 C1-6 할로알킬로부터 선택되며; 및
각각의 R20은 독립적으로 C1-6 알킬, C1-6 할로알킬, 할로, C1-6 알콕시, C1-6 할로알콕시, -OH, -NR17R18, -COR19 및 -CN으로부터 선택된다.
- 제 1 항에 있어서,
상기 A는
i) 전 방향족(fully aromatic)인 5- 또는 6-원 모노사이클릭 또는 9- 또는 10-원 바이사이클릭 헤테로아릴 고리, 및
ii) 포화 또는 부분 불포화된 카보사이클릭 또는 헤테로사이클릭 고리에 융합된 5- 또는 6-원 모노사이클릭 헤테로아릴 고리로 이루어진 9- 또는 10-원 바이사이클릭 헤테로아릴 고리로부터 선택되고: 상기 9- 또는 10-원 바이사이클릭 헤테로사이클릭 고리는 5- 또는 6-원 모노사이클릭 헤테로아릴 고리를 통해 분자의 잔기에 연결되며,
상기 A는 고리 A가 분자의 잔기에 부착되는 고리 원자에 인접한 위치에 하나의 고리 N 원자를 포함하고, 상기 A는 1개 내지 3개의 추가 고리 N 원자를 임의로 포함하며, 및 상기 A는 1개 또는 2개의 R2로 임의로 치환되고, 추가로 A는 하나의 R3으로 임의로 치환된다.
- 제 1 항에 있어서,
상기 A는 전 방향족인 5- 또는 6-원 모노사이클릭 또는 9- 또는 10-원 바이사이클릭 헤테로아릴 고리이고, 상기 A는 고리 A가 분자의 잔기에 부착되는 고리 원자에 인접한 위치에 하나의 고리 N 원자를 포함하고, 상기 A는 1개 내지 3개의 추가 고리 N 원자를 임의로 포함하며, 및 상기 A는 1개 또는 2개의 R2로 임의로 치환되고, 추가로 A는 하나의 R3으로 임의로 치환된다.
- 제 1 항 내지 제 9 항 중 어느 한 항에 있어서,
상기 m이 0인 화합물.
- 제 1 항 내지 제 10 항 중 어느 한 항에 있어서,
상기 R3은 -L1-R5, -L2-OR6, -L3-NR7R8, -CONR9R10, -NR11COR12 및 -Y-L7-NR7R8로부터 선택되는 화합물.
- 제 1 항 내지 제 11 항 중 어느 한 항에 있어서,
상기 R3은 -L1-R5인 화합물.
- 제 1 항 내지 제 11 항 중 어느 한 항에 있어서,
상기 R3은 -CONR9R10 또는 -NR11COR12인 화합물.
- 제 1 항 내지 제 11 항 중 어느 한 항에 있어서,
상기 R3은 -Y-L7-NR7R8이고, Y는 -O- 및 -NR13-로부터 선택되는 화합물.
- 제 1 항 내지 제 11 항 중 어느 한 항에 있어서,
상기 R3은 -OR6이고, 상기 R6은 -L1-R5이거나, 또는 R3은 -NR7R8이며, 상기 R7 또는 R8 중 하나는 -L1-R5인 화합물.
- 제 1 항 내지 제 11 항 중 어느 한 항에 있어서,
상기 R3은 -L2-OR6 또는 -L3-NR7R8이고, 상기 L2 및 L3은 각각 독립적으로 C1-6 알킬렌으로부터 선택되는 화합물.
- 제 1 항 내지 제 16 항 중 어느 한 항에 있어서,
각각의 R2는 독립적으로 C1-4 알킬, C1-4 할로알킬 및 -(C1-4 알킬렌)-OR4로부터 선택되는 화합물.
- 제 1 항에 있어서,
3-(2-(1-부틸-1H-피롤로[2,3-c]피리딘-5-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(1-프로필-1H-피롤로[2,3-c]피리딘-5-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
1-부틸-N,N-디메틸-5-(4-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)피리딘-2-일)-1H-피롤로[2,3-c]피리딘-2-카복사마이드,
N,N-디에틸-3-((4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-5-일)옥시)프로판-1-아민,
1-부틸-N-에틸-5-(4-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)피리딘-2-일)-1H-피롤로[2,3-c]피리딘-2-카복사마이드,
4-(3-((4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-5-일)옥시)프로필)모르폴린,
3-(5'-(3-(4,4-디플루오로피페리딘-1-일)프로폭시)-[2,2'-비피리딘]-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(3-(피페리딘-1-일메틸)-1-프로필-1H-피롤로[2,3-c]피리딘-5-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
4-((1-프로필-5-(4-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)피리딘-2- 일)-1H-피롤로[2,3-c]피리딘-3-일)메틸)모르폴린,
N-부틸-3-메톡시-N-(4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-5-일)프로판아마이드,
N-(사이클로프로필메틸)-N-메틸-4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-5-아민,
N1,N1-디에틸-N3-(4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-5-일)프로판-1,3-디아민,
N-(3-(4,4-디플루오로피페리딘-1-일)프로필)-N-메틸-4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-5-아민,
N,N-디에틸-3-(2-(4-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)피리딘-2-일)피리미딘-5-일옥시)프로판-1-아민,
N1,N1-디에틸-N3-메틸-N3-(4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-2,2'-비피리딘-5-일)프로판-1,3-디아민,
3-(2-(1-(테트라하이드로-2H-피란-4-일)-1H-피롤로[3,2-c]피리딘-6-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
N-에틸-N-펜에틸-3-((4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-5-일)옥시)프로판-1-아민,
2-페닐-N-(4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-5-일)아세트아마이드,
3-(2-(1-((테트라하이드로-2H-피란-4-일)메틸)-1H-피롤로[3,2-c]피리딘-6-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(4'-(2-(4,4-디플루오로피페리딘-1-일)에톡시)-[2,2'-비피리딘]-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
4-(2-((4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-4-일)옥시)에틸)모르폴린,
N,N,1-트리메틸-5-(4-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)피리딘-2-일)-1H-피롤로[2,3-c]피리딘-2-카복사마이드,
3-(2-(1-프로필-3-(1H-피라졸-4-일)-1H-피롤로[2,3-c]피리딘-5-일)피리딘-4- 일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
1-부틸-N,N-디에틸-5-(4-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)피리딘-2-일)-1H-피롤로[2,3-c]피리딘-2-카복사마이드,
3-(2-(1-(2-메톡시에틸)-1H-피롤로[2,3-c]피리딘-5-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
2-(4,4-디플루오로피페리딘-1-일)-N-(4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-4-일)아세트아마이드,
N-(2-(4,4-디플루오로피페리딘-1-일)에틸)-4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-4-아민,
3-(2-(3-(피페리딘-1-일메틸)-1H-피라졸로[3,4-c]피리딘-5-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(1-(2-(4,4-디플루오로피페리딘-1-일)에틸)-1H-피롤로[3,2-c]피리딘-6-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
1-메틸-N-(4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-5-일)피페리딘-4-카복사마이드,
3-페닐-N-(4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-4-일)프로판아마이드,
2-사이클로부틸-N-(4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-4-일)아세트아마이드,
N-(피페리딘-3-일)-4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-4-카복사마이드,
3-(5'-(3-(1H-피라졸-1-일)프로폭시)-[2,2'-비피리딘]-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
(1-프로필-5-(4-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)피리딘-2-일)-1H-피롤로[2,3-c]피리딘-3-일)메탄올,
3-(2-(3-(메톡시메틸)-1-프로필-1H-피롤로[2,3-c]피리딘-5-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
4-((1-프로필-5-(4-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)피리딘-2-일)-1H-피롤로[2,3-c]피리딘-3-일)메틸)모르폴린,
3-(2-(1H-피롤로[3,2-c]피리딘-6-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(1-(피리딘-4-일메틸)-1H-피롤로[3,2-c]피리딘-6-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
N-((1-메틸피페리딘-4-일)메틸)-4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-4-카복사마이드,
N-((1-메틸피페리딘-4-일)메틸)-4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-5-카복사마이드,
3-(2-(1-(1-(2,2,2-트리플루오로에틸)피페리딘-4-일)-1H-피롤로[3,2-c]피리딘-6-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(1-메틸-3-(1H-피라졸-4-일)-1H-피롤로[2,3-c]피리딘-5-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(1-부틸-3-(1-메틸-1,2,3,6-테트라하이드로피리딘-4-일)-1H-피롤로[2,3-c]피리딘-5-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
N-메틸-3-(4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-2,2'-비피리딘-5-일옥시)프로판-1-아민,
1-(1-부틸-5-(4-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)피리딘-2-일)-1H-피롤로[2,3-c]피리딘-3-일)-N, N-디메틸메탄아민,
3-(2-(1H-피라졸로[4,3-b]피리딘-3-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
N-(4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-4-일)피페리딘-3-카복사마이드,
1-(2-메톡시에틸)-N,N-디메틸-5-(4-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)피리딘-2-일)-1H-피롤로[2,3-c]피리딘-2-카복사마이드,
3-(2-(1-(2-메톡시에틸)-3-(1H-피라졸-4-일)-1H-피롤로[2,3-c]피리딘-5-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(1-메틸-1H-피롤로[2,3-c]피리딘-5-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(1-(2-메톡시에틸)-1H-피롤로[3,2-c]피리딘-6-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(1-(피리딘-3-일메틸)-1H-피롤로[3,2-c]피리딘-6-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(1-(피리딘-2-일메틸)-1H-피롤로[3,2-c]피리딘-6-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
2-(메틸(3-((4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-5-일)옥시)프로필)아미노)에탄-1-올,
3-(2-(1-(2-메톡시에틸)-1H-피라졸로[3,4-c]피리딘-5-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(2-(2-메톡시에틸)-2H-피라졸로[3,4-c]피리딘-5-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(1H-피라졸로[3,4-b]피리딘-1-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
N,N-디메틸-3-((4'-(5-(트리플루오로메틸)-1,2,4-옥사디아졸-3-일)-[2,2'-비피리딘]-5-일)옥시)프로판-1-아민,
3-(2-(1-메틸-1H-피라졸로[4,3-b]피리딘-3-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(1-(2-메톡시에틸)-1H-피라졸로[4,3-b]피리딘-3-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(1-에틸-1H-피라졸로[4,3-b]피리딘-3-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸,
3-(2-(1-(2-(1-메틸-1H-이미다졸-2-일)에틸)-1H-피라졸로[4,3-b]피리딘-3-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸, 및
3-(2-(1-((1-메틸-1H-피라졸-4-일)메틸)-1H-피롤로[3,2-c]피리딘-6-일)피리딘-4-일)-5-(트리플루오로메틸)-1,2,4-옥사디아졸로부터 선택된 화합물, 또는 이의 염인 화합물.
- 제 1 항 내지 제 18 항 중 어느 한 항의 화합물 또는 이의 약제학적으로 허용가능한 염, 및 약제학적으로 허용가능한 담체를 포함하는 약제학적 조성물.
- 의약으로 사용하기 위한, 제 1 항 내지 제 18 항 중 어느 한 항의 화합물, 또는 이의 약제학적으로 허용가능한 염.
- HDAC6과 관련된 질환의 치료에 사용하기 위한, 제 1 항 내지 제 18 항 중 어느 한 항의 화합물, 또는 이의 약제학적으로 허용가능한 염, 또는 제 19 항의 약제학적 조성물.
- 암, 자가면역 또는 염증성 질환, 이식 거부, 섬모병증(ciliopathy), 신경계 질환, 정신 또는 행동 장애, 감염성 질환, 심혈관 질환, 근육 위축증 또는 악액질로부터 선택된 질환의 치료에 사용하기 위한, 제 1 항 내지 제 18 항 중 어느 한 항의 화합물, 또는 이의 약제학적으로 허용가능한 염, 또는 제 19 항의 약제학적 조성물.
- 치료 유효량의 제 1 항 내지 제 18 항 중 어느 한 항의 화합물, 또는 이의 약제학적으로 허용가능한 염을 이를 필요로 하는 환자에게 투여하는 것을 포함하는, HDAC6과 관련된 질환의 치료 방법.
- 치료 유효량의 제 1 항 내지 제 18 항 중 어느 한 항의 화합물, 또는 이의 약제학적으로 허용가능한 염을 이를 필요로 하는 환자에게 투여하는 것을 포함하는, 암, 자가면역 또는 염증성 질환, 이식 거부, 섬모병증(ciliopathy), 신경계 질환, 정신 또는 행동 장애, 감염성 질환, 심혈관 질환, 근육 위축증 또는 악액질로부터 선택된 질환의 치료 방법.
- HDAC6과 관련된 질환의 치료용 의약 제조를 위한, 제 1 항 내지 제 18 항 중 어느 한 항의 화합물, 또는 이의 약제학적으로 허용가능한 염의 용도.
- 암, 자가면역 또는 염증성 질환, 이식 거부, 섬모병증(ciliopathy), 신경계 질환, 정신 또는 행동 장애, 감염성 질환, 심혈관 질환, 근육 위축증 또는 악액질로부터 선택된 질환의 치료용 의약 제조를 위한, 제 1 항 내지 제 18 항 중 어느 한 항의 화합물, 또는 이의 약제학적으로 허용가능한 염의 용도.
- HDAC6과 관련된 질환 치료를 위한, 제 1 항 내지 제 18 항 중 어느 한 항의 화합물, 또는 이의 약제학적으로 허용가능한 염의 용도.
- 암, 자가면역 또는 염증성 질환, 이식 거부, 섬모병증(ciliopathy), 신경계 질환, 정신 또는 행동 장애, 감염성 질환, 심혈관 질환, 근육 위축증 또는 악액질로부터 선택된 질환 치료를 위한, 제 1 항 내지 제 18 항 중 어느 한 항의 화합물, 또는 이의 약제학적으로 허용가능한 염의 용도.
- 치료될 환자는 인간인, 제 20 항 내지 제 22 항 중 어느 한 항에 따라 사용하기 위한 화합물, 또는 제 21 항 또는 제 22 항에 따라 사용하기 위한 약제학적 조성물, 또는 제 23 항 또는 제 24 항의 방법, 또는 제 25 항 내지 제 28 항 중 어느 한 항의 용도.
- 제 1 항 내지 제 18 항 중 어느 한 항의 화합물, 또는 이의 약제학적으로 허용가능한 염을 샘플에 적용하는 것을 포함하는, HDAC6를 억제하는 인 비트로 방법.
- HDAC6 억제제로서, 제 1 항 내지 제 18 항 중 어느 한 항의 화합물, 또는 이의 약제학적으로 허용가능한 염의 인 비트로 용도.
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WO2020245381A1 (en) * | 2019-06-06 | 2020-12-10 | Oryzon Genomics, S.A. | 3-(2-(heteroaryl)-pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole derivatives as hdac6 inhibitors |
CA3165424A1 (en) | 2019-12-20 | 2021-06-24 | Tenaya Therapeutics, Inc. | Fluoroalkyl-oxadiazoles and uses thereof |
KR102576148B1 (ko) * | 2020-04-13 | 2023-09-07 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 유도체 화합물 및 이를 포함하는 약제학적 조성물 |
KR102685058B1 (ko) * | 2020-09-02 | 2024-07-15 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 새로운 구조의 화합물 및 이를 포함하는 약제학적 조성물 |
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