KR100853974B1 - 7-아미노-3-페닐 디히드로피리미도[4,5-d]피리미디논의아미드 유도체, 그의 제조 방법 및 약학제로서의 용도 - Google Patents
7-아미노-3-페닐 디히드로피리미도[4,5-d]피리미디논의아미드 유도체, 그의 제조 방법 및 약학제로서의 용도 Download PDFInfo
- Publication number
- KR100853974B1 KR100853974B1 KR1020077004573A KR20077004573A KR100853974B1 KR 100853974 B1 KR100853974 B1 KR 100853974B1 KR 1020077004573 A KR1020077004573 A KR 1020077004573A KR 20077004573 A KR20077004573 A KR 20077004573A KR 100853974 B1 KR100853974 B1 KR 100853974B1
- Authority
- KR
- South Korea
- Prior art keywords
- phenyl
- methyl
- amino
- chloro
- pyrimido
- 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.)
- Expired - Fee Related
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- -1 Amide derivatives of 7-amino-3-phenyl dihydropyrimido [4,5-d] pyrimidinone Chemical class 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 96
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000003814 drug Substances 0.000 claims abstract description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 125000004076 pyridyl group Chemical group 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- OTVKTJJPNUHFOE-UHFFFAOYSA-N 4-[3-[(4-acetylpiperazin-1-yl)methyl]phenyl]-n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]benzamide Chemical compound C1C2=CN=C(N)N=C2N(C)C(=O)N1C(C(=CC=1)Cl)=CC=1NC(=O)C(C=C1)=CC=C1C(C=1)=CC=CC=1CN1CCN(C(C)=O)CC1 OTVKTJJPNUHFOE-UHFFFAOYSA-N 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- WPAHNJNYNRNGRO-UHFFFAOYSA-N n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]-1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)NC=3C=C(C(=CC=3)Cl)N3C(=O)N(C4=NC(N)=NC=C4C3)C)=CC2=C1 WPAHNJNYNRNGRO-UHFFFAOYSA-N 0.000 claims description 3
- CXRVRCKJFRVCLL-UHFFFAOYSA-N n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]-1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)NC=3C=C(C(=CC=3)Cl)N3C(=O)N(C4=NC(N)=NC=C4C3)C)=CC2=C1 CXRVRCKJFRVCLL-UHFFFAOYSA-N 0.000 claims description 3
- JZZOFSRCIODRKJ-UHFFFAOYSA-N n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]-2-phenylbenzamide Chemical compound C1C2=CN=C(N)N=C2N(C)C(=O)N1C(C(=CC=1)Cl)=CC=1NC(=O)C1=CC=CC=C1C1=CC=CC=C1 JZZOFSRCIODRKJ-UHFFFAOYSA-N 0.000 claims description 3
- TXRLMWBVQKUXFP-UHFFFAOYSA-N n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]-2-pyridin-2-ylacetamide Chemical compound C1C2=CN=C(N)N=C2N(C)C(=O)N1C(C(=CC=1)Cl)=CC=1NC(=O)CC1=CC=CC=N1 TXRLMWBVQKUXFP-UHFFFAOYSA-N 0.000 claims description 3
- BNNSIZKZNCRBHE-UHFFFAOYSA-N n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]-2-pyridin-3-ylacetamide Chemical compound C1C2=CN=C(N)N=C2N(C)C(=O)N1C(C(=CC=1)Cl)=CC=1NC(=O)CC1=CC=CN=C1 BNNSIZKZNCRBHE-UHFFFAOYSA-N 0.000 claims description 3
- YBGNLDUVGQYSRK-UHFFFAOYSA-N n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]-3-(2-hydroxyphenyl)propanamide Chemical compound C1C2=CN=C(N)N=C2N(C)C(=O)N1C(C(=CC=1)Cl)=CC=1NC(=O)CCC1=CC=CC=C1O YBGNLDUVGQYSRK-UHFFFAOYSA-N 0.000 claims description 3
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- VNAMSEQOWKVMFM-UHFFFAOYSA-N n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]-3-phenylbenzamide Chemical compound C1C2=CN=C(N)N=C2N(C)C(=O)N1C(C(=CC=1)Cl)=CC=1NC(=O)C(C=1)=CC=CC=1C1=CC=CC=C1 VNAMSEQOWKVMFM-UHFFFAOYSA-N 0.000 claims description 3
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- PLHOJVHVLODALK-UHFFFAOYSA-N n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]-3-pyridin-2-ylprop-2-enamide Chemical compound C1C2=CN=C(N)N=C2N(C)C(=O)N1C(C(=CC=1)Cl)=CC=1NC(=O)C=CC1=CC=CC=N1 PLHOJVHVLODALK-UHFFFAOYSA-N 0.000 claims description 3
- SQGYAXODTUCZPV-UHFFFAOYSA-N n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]-3-pyridin-3-ylpropanamide Chemical compound C1C2=CN=C(N)N=C2N(C)C(=O)N1C(C(=CC=1)Cl)=CC=1NC(=O)CCC1=CC=CN=C1 SQGYAXODTUCZPV-UHFFFAOYSA-N 0.000 claims description 3
- MUKJSPNJFAXXAQ-UHFFFAOYSA-N n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]-4-(1h-pyrrol-2-yl)benzamide Chemical compound C1C2=CN=C(N)N=C2N(C)C(=O)N1C(C(=CC=1)Cl)=CC=1NC(=O)C(C=C1)=CC=C1C1=CC=CN1 MUKJSPNJFAXXAQ-UHFFFAOYSA-N 0.000 claims description 3
- HIXLPVKKBOGNMU-UHFFFAOYSA-N n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]-4-(4-methylpiperazin-1-yl)benzamide Chemical compound C1CN(C)CCN1C1=CC=C(C(=O)NC=2C=C(C(Cl)=CC=2)N2C(N(C)C3=NC(N)=NC=C3C2)=O)C=C1 HIXLPVKKBOGNMU-UHFFFAOYSA-N 0.000 claims description 3
- CBSTTWKHSVKVCU-UHFFFAOYSA-N n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]-4-[3-(morpholin-4-ylmethyl)phenyl]benzamide Chemical compound C1C2=CN=C(N)N=C2N(C)C(=O)N1C(C(=CC=1)Cl)=CC=1NC(=O)C(C=C1)=CC=C1C(C=1)=CC=CC=1CN1CCOCC1 CBSTTWKHSVKVCU-UHFFFAOYSA-N 0.000 claims description 3
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- IDTUWXBMLKVIEO-UHFFFAOYSA-N n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]-4-phenylbutanamide Chemical compound C1C2=CN=C(N)N=C2N(C)C(=O)N1C(C(=CC=1)Cl)=CC=1NC(=O)CCCC1=CC=CC=C1 IDTUWXBMLKVIEO-UHFFFAOYSA-N 0.000 claims description 3
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- CKKGTJAHSLTKFY-UHFFFAOYSA-N n-[3-(7-amino-1-methyl-2-oxo-4h-pyrimido[4,5-d]pyrimidin-3-yl)-4-chlorophenyl]cycloheptanecarboxamide Chemical compound C1C2=CN=C(N)N=C2N(C)C(=O)N1C(C(=CC=1)Cl)=CC=1NC(=O)C1CCCCCC1 CKKGTJAHSLTKFY-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61K31/495—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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- 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
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
실시예 번호 | IC50 src (nM) | IC50 lck (nM) |
2-7 | 73.5 | 168 |
2-14 | 41 | 38.5 |
1, 2-3, 2-15, 2-22, 2-24 | 50-150 | 50-150 |
실시예 번호 | 화합물 명 | 1 H- NMR |
2-1 | 시클로헥산카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드 | |
2-2 | 시클로헵탄카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드 | |
2-3 | 비페닐-3-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드 | |
2-4 | 비페닐-2-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드 | |
2-5 | 4'-시아노-비페닐-4-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드 |
실시예 번호 | 화합물 명 | 1 H- NMR |
2-6 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-4-(4-메틸-피페라진-1-일)-벤즈아미드 | |
2-7 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-4-모르폴린-4-일-벤즈아미드 | |
2-8 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-4-시아노-벤즈아미드 | |
2-9 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-4-페닐-부티르아미드 | |
2-10 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-3-페닐-프로피온아미드 |
실시예 번호 | 화합물 명 | 1 H- NMR |
2-11 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-3-(2-히드록시-페닐)-프로피온아미드 | |
2-12 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-3-(3-아미노-페닐)-프로피온아미드 | |
2-13 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-3-(4-아미노-페닐)-프로피온아미드 | |
2-14 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-3-페닐-아크릴아미드 | |
2-15 | 나프탈렌-1-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드 | |
2-16 | 1H-인돌-2-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드 |
실시예 번호 | 화합물 명 | 1 H- NMR |
2-17 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-2-피리딘-3-일-아세트아미드 | |
2-18 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-2-피리딘-2-일-아세트아미드 | |
2-19 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-3-피리딘-3-일-프로피온아미드 | |
2-20 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-3-피리딘-2-일-아크릴아미드 | |
2-21 | 벤조[b]티오펜-2-카르복실산 (4-클로로-3-{7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일}-페닐)-아미드 | |
2-22 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-4-피리딘-2-일-벤즈아미드 |
실시예 번호 | 화합물 명 | 1 H- NMR |
2-23 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-4-피리딘-4-일-벤즈아미드 | |
2-24 | N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-4-(1H-피롤-2-일)-벤즈아미드 | |
2-25 | 4'-모르폴린-4-일메틸-비페닐-4-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드 | |
2-26 | 3'-(4-메틸-피페라진-1-일메틸)-비페닐-4-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드 | |
2-27 | 3'-(4-아세틸-피페라진-1-일메틸)-비페닐-4-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드 | |
2-28 | 3'-모르폴린-4-일메틸-비페닐-4-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드 | |
2-29 | 3'-(1-카르바모일-에틸술파닐)-비페닐-4-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드 |
실시예 번호 | 화합물 명 | 1 H- NMR |
2-30 | 3'-(2-디메틸아미노-에톡시)-비페닐-4-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드; 아세트산과의 화합물 |
Claims (13)
- 하기 화학식 I 의 화합물 및 그의 약학적으로 허용가능한 염:[화학식 I][식 중,R1 은 불소 또는 염소이고;Q 는 C1-C3 알킬렌 또는 비닐렌이고;n 은 0 또는 1 이고;R2 는 C6-C7 시클로알킬; 시아노, 히드록시, 아미노, 메틸 피페라지닐, 모르폴리닐, 피리디닐 또는 피롤릴로 치환되거나 또는 치환되지 아니한 페닐; 시아노, 4'-모르폴리닐메틸, 3'-(4-메틸-피페라지닐메틸), 3'-(4-아세틸-피페라지닐메틸), 3'-모르폴리닐메틸, 3'-(카르바모일-에틸술파닐) 또는 3'-(디메틸아미노-에톡시) 로 치환되거나 또는 치환되지 아니한 비페닐; 나프탈렌; 인돌; 피리디닐, 또는 벤조티오펜임].
- 제 1 항에 있어서, n 이 0 인 화합물.
- 제 1 항에 있어서, n 이 1 인 화합물.
- 제 1 항에 있어서, R1 이 염소인 화합물.
- 삭제
- 제 1 항 내지 제 4 항 중 어느 한 항에 있어서, 하기와 같은 화합물:시클로헥산카르복실산 (4-클로로-3-{7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일}-페닐)-아미드; 아세트산과의 화합물;시클로헵탄카르복실산 (4-클로로-3-{7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일}-페닐)-아미드; 아세트산과의 화합물;비페닐-4-카르복실산 (4-클로로-3-{7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일}-페닐)-아미드;비페닐-2-카르복실산 (4-클로로-3-{7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일}-페닐)-아미드; 아세트산과의 화합물;비페닐-3-카르복실산 (4-클로로-3-{7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일}-페닐)-아미드; 아세트산과의 화합물;4'-시아노-비페닐-3-카르복실산 (4-클로로-3-{7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일}-페닐)-아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3 -일)-4-클로로-페닐]-4-(4-메틸-피페라진-1-일)-벤즈아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-4-모르폴린-4-일-벤즈아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-4-시아노-벤즈아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-4-페닐-부티르아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-3-페닐-프로피온아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-3-(2-히드록시-페닐)-프로피온아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-3-(3-아미노-페닐)-프로피온아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-3-(4-아미노-페닐)-프로피온아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-3-페닐-아크릴아미드;나프탈렌-1-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드;1H-인돌-2-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-2-피리딘-3-일-아세트아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-2-피리딘-2-일-아세트아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-3-피리딘-3-일-프로피온아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-3-피리딘-2-일-아크릴아미드;벤조[b]티오펜-2-카르복실산 (4-클로로-3-{7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일}-페닐)-아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-4-피리딘-2-일-벤즈아미드;N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-4-피리딘-4-일-벤즈아미드; 및N-[3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-4-(1H-피롤-2-일)-벤즈아미드.
- 제 1 항 내지 제 4 항 중 어느 한 항에 있어서, n 이 0 이고; R2 가 4'-모르폴리닐메틸, 3'-(4-메틸-피페라지닐메틸), 3'-(4-아세틸-피페라지닐메틸), 3'-모르폴리닐메틸, 3'-(카르바모일-에틸술파닐) 또는 3'-(디메틸아미노-에톡시) 로 치환된 비페닐인 화합물.
- 제 7 항에 있어서, 하기와 같은 화합물:4'-모르폴린-4-일메틸-비페닐-4-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드;3'-(4-메틸-피페라진-1-일메틸)-비페닐-4-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드;3'-(4-아세틸-피페라진-1-일메틸)-비페닐-4-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드;3'-모르폴린-4-일메틸-비페닐-4-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드;3'-(1-카르바모일-에틸술파닐)-비페닐-4-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드; 및3'-(2-디메틸아미노-에톡시)-비페닐-4-카르복실산 [3-(7-아미노-1-메틸-2-옥소-1,4-디히드로-2H-피리미도[4,5-d]피리미딘-3-일)-4-클로로-페닐]-아미드; 아세트산과의 화합물.
- 하기와 같은, 화학식 I 의 화합물의 제조 방법:(a) 하기 화학식 II 의 화합물 중의 아미노기를,[화학식 II][식 중, R1 는 제 1 항에 제시된 의미를 가짐]하기 화학식 III 의 카르복실산과 반응시켜,[화학식 III][식 중, R2, Q 및 n 은 제 1 항에 제시된 의미를 가짐]하기 화학식 IV 의 아미드 유도체를 산출함:[화학식 IV][식 중, R1, R2, Q 및 n 은 제 1 항에 제시된 의미를 가짐](b) 메틸술포닐기를 해당하는 아민으로 전환시켜, 하기 화학식 I 의 화합물을 산출함:[화학식 I][식 중, R1, R2, Q 및 n 은 제 1 항에 제시된 의미를 가짐](c) 원하는 경우, 상기 화학식 I 의 화합물을 약학적으로 허용가능한 염으로 전환시킴.
- 약학적으로 허용가능한 아쥬반트와 함께 활성 성분으로서 제 1 항 내지 제 4 항 중 어느 한 항에 따른 1 종 이상의 화합물을 함유하는 암 치료용 의약.
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US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
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HK1220357A1 (zh) | 2013-03-15 | 2017-05-05 | Celgene Car Llc | 雜芳基化合物和其用途 |
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MX393494B (es) | 2013-04-19 | 2025-03-24 | Incyte Holdings Corp | Heterociclos biciclicos como inhibidores de los receptores del factor de crecimiento de fibroblastos (fgfr). |
MA38393B1 (fr) | 2014-03-13 | 2018-11-30 | Sanofi Sa | Composés hétéroaryle et utilisations associées |
US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
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WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
KR101818130B1 (ko) | 2016-08-09 | 2018-01-12 | 한국과학기술연구원 | 1,3,7-삼치환된 3,4-다이하이드로피리미도[4,5-d]피리미딘-2(1H)-온 유도체가 포함된 급성골수성백혈병 치료제 |
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WO2021076602A1 (en) | 2019-10-14 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
JP2023505258A (ja) | 2019-12-04 | 2023-02-08 | インサイト・コーポレイション | Fgfr阻害剤としての三環式複素環 |
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WO2004011465A1 (en) * | 2002-07-25 | 2004-02-05 | Warner-Lambert Company Llc | Kinase inhibitors |
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RU2007111758A (ru) | 2008-10-10 |
US7494993B2 (en) | 2009-02-24 |
US20080032970A1 (en) | 2008-02-07 |
EP1789417A1 (en) | 2007-05-30 |
JP2008509964A (ja) | 2008-04-03 |
MX2007002089A (es) | 2007-03-29 |
CA2576924A1 (en) | 2006-03-09 |
KR20070039608A (ko) | 2007-04-12 |
CN1984914A (zh) | 2007-06-20 |
BRPI0514750A (pt) | 2008-06-24 |
AU2005279337A1 (en) | 2006-03-09 |
WO2006024487A1 (en) | 2006-03-09 |
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