KR20140054246A - 키나제 억제제로서의 아미노 퀴나졸린 - Google Patents
키나제 억제제로서의 아미노 퀴나졸린 Download PDFInfo
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- KR20140054246A KR20140054246A KR1020147006731A KR20147006731A KR20140054246A KR 20140054246 A KR20140054246 A KR 20140054246A KR 1020147006731 A KR1020147006731 A KR 1020147006731A KR 20147006731 A KR20147006731 A KR 20147006731A KR 20140054246 A KR20140054246 A KR 20140054246A
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- South Korea
- Prior art keywords
- alkyl
- alkoxy
- hydroxy
- phenyl
- group
- 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.)
- Ceased
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- 229940043355 kinase inhibitor Drugs 0.000 title description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
- CZAAKPFIWJXPQT-UHFFFAOYSA-N quinazolin-2-amine Chemical class C1=CC=CC2=NC(N)=NC=C21 CZAAKPFIWJXPQT-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 218
- 238000000034 method Methods 0.000 claims abstract description 50
- -1 cyano, hydroxyl Chemical group 0.000 claims description 301
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 221
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 169
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 132
- 229910052736 halogen Inorganic materials 0.000 claims description 128
- 150000003839 salts Chemical class 0.000 claims description 104
- 150000002367 halogens Chemical class 0.000 claims description 95
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 76
- 125000003545 alkoxy group Chemical group 0.000 claims description 70
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 61
- 125000005843 halogen group Chemical group 0.000 claims description 58
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 57
- 125000001072 heteroaryl group Chemical group 0.000 claims description 55
- 125000001424 substituent group Chemical group 0.000 claims description 53
- 102100022502 Receptor-interacting serine/threonine-protein kinase 2 Human genes 0.000 claims description 52
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 51
- 239000000203 mixture Substances 0.000 claims description 49
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 47
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 44
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 42
- 101001109137 Homo sapiens Receptor-interacting serine/threonine-protein kinase 2 Proteins 0.000 claims description 41
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 38
- 229910052757 nitrogen Inorganic materials 0.000 claims description 38
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 37
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 33
- 125000004429 atom Chemical group 0.000 claims description 31
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 30
- 238000011282 treatment Methods 0.000 claims description 30
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 29
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 27
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 26
- 125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims description 25
- 125000006568 (C4-C7) heterocycloalkyl group Chemical group 0.000 claims description 25
- 125000005842 heteroatom Chemical group 0.000 claims description 25
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 25
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 23
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 21
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 21
- 208000035475 disorder Diseases 0.000 claims description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 230000001404 mediated effect Effects 0.000 claims description 18
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 18
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 16
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 239000001301 oxygen Substances 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 14
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 12
- 208000009766 Blau syndrome Diseases 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 11
- 125000005605 benzo group Chemical group 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims description 8
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 8
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 7
- 201000000306 sarcoidosis Diseases 0.000 claims description 7
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 6
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 claims description 5
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 5
- 206010046851 Uveitis Diseases 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 5
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 4
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
- 101150065749 Churc1 gene Proteins 0.000 claims description 4
- 102100038239 Protein Churchill Human genes 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 125000002837 carbocyclic group Chemical group 0.000 claims description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 3
- 108090000426 Caspase-1 Proteins 0.000 claims description 3
- 201000004624 Dermatitis Diseases 0.000 claims description 3
- 208000029523 Interstitial Lung disease Diseases 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- TVCQPRRPKVXBKS-UHFFFAOYSA-N n-(6-propan-2-ylsulfonylquinazolin-4-yl)-1,3-benzothiazol-5-amine Chemical compound C1=C2SC=NC2=CC(NC2=NC=NC3=CC=C(C=C32)S(=O)(=O)C(C)C)=C1 TVCQPRRPKVXBKS-UHFFFAOYSA-N 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
- YCCZZOAPFODSFP-UHFFFAOYSA-N 4-(2-phenoxyphenyl)-1H-quinazolin-4-amine Chemical compound N1C=NC2=CC=CC=C2C1(N)C1=CC=CC=C1OC1=CC=CC=C1 YCCZZOAPFODSFP-UHFFFAOYSA-N 0.000 claims description 2
- OCEPZXZVPNPKJD-UHFFFAOYSA-N 6-methylsulfanyl-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound C12=CC(SC)=CC=C2N=CN=C1NC(C=C1)=CC=C1OCC1=CC=CC=C1 OCEPZXZVPNPKJD-UHFFFAOYSA-N 0.000 claims description 2
- DDAXBPLLWRSPCR-UHFFFAOYSA-N 6-methylsulfinyl-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound C12=CC(S(=O)C)=CC=C2N=CN=C1NC(C=C1)=CC=C1OCC1=CC=CC=C1 DDAXBPLLWRSPCR-UHFFFAOYSA-N 0.000 claims description 2
- ZUXSZSSULHQTPT-UHFFFAOYSA-N 6-methylsulfonyl-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound C12=CC(S(=O)(=O)C)=CC=C2N=CN=C1NC(C=C1)=CC=C1OCC1=CC=CC=C1 ZUXSZSSULHQTPT-UHFFFAOYSA-N 0.000 claims description 2
- OWLZCGFAMIEPQO-UHFFFAOYSA-N CC1=C(C=CC=C1)N1CN=C2C=CC(=CC2=C1N)SC Chemical compound CC1=C(C=CC=C1)N1CN=C2C=CC(=CC2=C1N)SC OWLZCGFAMIEPQO-UHFFFAOYSA-N 0.000 claims description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 2
- 206010069351 acute lung injury Diseases 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 208000024908 graft versus host disease Diseases 0.000 claims description 2
- OAZJURONLYELCO-UHFFFAOYSA-N n-[(3-fluoro-4-methoxyphenyl)methyl]-6-methylsulfanylquinazolin-4-amine Chemical compound C1=C(F)C(OC)=CC=C1CNC1=NC=NC2=CC=C(SC)C=C12 OAZJURONLYELCO-UHFFFAOYSA-N 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims 1
- 206010003827 Autoimmune hepatitis Diseases 0.000 claims 1
- 206010063837 Reperfusion injury Diseases 0.000 claims 1
- 208000026594 alcoholic fatty liver disease Diseases 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 230000000302 ischemic effect Effects 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 1
- 125000005415 substituted alkoxy group Chemical group 0.000 claims 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 114
- 239000000243 solution Substances 0.000 description 88
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- 238000006243 chemical reaction Methods 0.000 description 68
- 239000007787 solid Substances 0.000 description 60
- 239000011541 reaction mixture Substances 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- 238000004440 column chromatography Methods 0.000 description 27
- 239000002904 solvent Substances 0.000 description 24
- 239000000047 product Substances 0.000 description 22
- 239000013058 crude material Substances 0.000 description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 125000001041 indolyl group Chemical group 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 241000700159 Rattus Species 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
- 108010079933 Receptor-Interacting Protein Serine-Threonine Kinase 2 Proteins 0.000 description 13
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 125000004122 cyclic group Chemical group 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
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- 239000000543 intermediate Substances 0.000 description 11
- HKYLKSMCVOFYTL-UHFFFAOYSA-N n-(6-tert-butylsulfonylquinazolin-4-yl)-1,3-benzothiazol-5-amine Chemical compound C1=C2SC=NC2=CC(NC2=NC=NC3=CC=C(C=C32)S(=O)(=O)C(C)(C)C)=C1 HKYLKSMCVOFYTL-UHFFFAOYSA-N 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- UJZYHMZRXGNDFB-UHFFFAOYSA-N 1,3-benzothiazol-5-amine Chemical compound NC1=CC=C2SC=NC2=C1 UJZYHMZRXGNDFB-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 10
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- 102000004127 Cytokines Human genes 0.000 description 9
- 108090000695 Cytokines Proteins 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
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- 150000001412 amines Chemical class 0.000 description 8
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 8
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- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 7
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- 239000012267 brine Substances 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
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- 101001125026 Homo sapiens Nucleotide-binding oligomerization domain-containing protein 2 Proteins 0.000 description 6
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
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- 238000002560 therapeutic procedure Methods 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
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- 208000023275 Autoimmune disease Diseases 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
- 101001125032 Homo sapiens Nucleotide-binding oligomerization domain-containing protein 1 Proteins 0.000 description 4
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Images
Classifications
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| KR20230003439A (ko) | 2020-05-28 | 2023-01-05 | 코스이 후카야 | 감귤류 과실 제조 방법 및 감귤류 과실 |
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| SG192769A1 (en) | 2011-03-04 | 2013-09-30 | Glaxosmithkline Ip No 2 Ltd | Amino-quinolines as kinase inhibitors |
| TWI547494B (zh) | 2011-08-18 | 2016-09-01 | 葛蘭素史克智慧財產發展有限公司 | 作為激酶抑制劑之胺基喹唑啉類 |
| TWI592417B (zh) | 2012-09-13 | 2017-07-21 | 葛蘭素史克智慧財產發展有限公司 | 胺基喹唑啉激酶抑制劑之前藥 |
| AR092530A1 (es) | 2012-09-13 | 2015-04-22 | Glaxosmithkline Llc | Compuesto de amino-quinolina, composicion farmaceutica que lo comprende y uso de dicho compuesto para la preparacion de un medicamento |
| JP6301374B2 (ja) | 2013-02-21 | 2018-03-28 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | キナーゼ阻害剤としてのキナゾリン類 |
| CN105228625A (zh) * | 2013-03-15 | 2016-01-06 | 昂科迪塞恩股份有限公司 | 大环rip2激酶抑制剂 |
| WO2016042087A1 (en) * | 2014-09-17 | 2016-03-24 | Oncodesign S.A. | Macrocyclic rip2 kinase inhibitors |
| GB201506872D0 (en) * | 2015-04-22 | 2015-06-03 | Ge Oil & Gas Uk Ltd | Novel compounds |
| TWI730959B (zh) | 2015-05-19 | 2021-06-21 | 英商葛蘭素史克智慧財產發展有限公司 | 作為激酶抑制劑之雜環醯胺 |
| GB201516243D0 (en) | 2015-09-14 | 2015-10-28 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| CN109311867A (zh) * | 2016-04-20 | 2019-02-05 | 葛兰素史克知识产权开发有限公司 | 包含ripk2抑制剂的共轭物 |
| JP7101177B2 (ja) | 2017-01-10 | 2022-07-14 | バイエル・アクチエンゲゼルシヤフト | 有害生物防除剤としてのヘテロサイクレン誘導体 |
| MX2019008230A (es) | 2017-01-10 | 2019-10-24 | Bayer Ag | Derivados heterociclicos como agentes de control de plagas. |
| WO2020043122A1 (zh) * | 2018-08-28 | 2020-03-05 | 南京明德新药研发有限公司 | 作为rip2激酶抑制剂的喹唑啉类衍生物 |
| WO2020094613A1 (en) | 2018-11-06 | 2020-05-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Nod2 inhibitors for the treatment of hereditary periodic fevers |
| US20230247994A1 (en) | 2020-07-02 | 2023-08-10 | Bayer Aktiengesellschaft | Heterocyclene derivatives as pest control agents |
| CN114014890A (zh) * | 2021-03-12 | 2022-02-08 | 爱科诺生物医药(香港)有限公司 | 具有rip2激酶抑制活性的化合物,包含其的药物组合物,及其应用 |
| WO2024059169A1 (en) * | 2022-09-14 | 2024-03-21 | Blueprint Medicines Corporation | Egfr inhibitors |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| KR20230003439A (ko) | 2020-05-28 | 2023-01-05 | 코스이 후카야 | 감귤류 과실 제조 방법 및 감귤류 과실 |
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