JP2009535393A - 置換2−アミノ縮合複素環式化合物 - Google Patents
置換2−アミノ縮合複素環式化合物 Download PDFInfo
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- JP2009535393A JP2009535393A JP2009508525A JP2009508525A JP2009535393A JP 2009535393 A JP2009535393 A JP 2009535393A JP 2009508525 A JP2009508525 A JP 2009508525A JP 2009508525 A JP2009508525 A JP 2009508525A JP 2009535393 A JP2009535393 A JP 2009535393A
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- Prior art keywords
- aryl
- membered
- compound
- alkyl
- heterocyclyl
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- 150000002391 heterocyclic compounds Chemical class 0.000 title description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 250
- 238000000034 method Methods 0.000 claims abstract description 52
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 239000012453 solvate Substances 0.000 claims abstract description 17
- 241000124008 Mammalia Species 0.000 claims abstract description 10
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 230000001404 mediated effect Effects 0.000 claims abstract description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 85
- 125000003118 aryl group Chemical group 0.000 claims description 61
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 60
- -1 azido, hydroxy Chemical group 0.000 claims description 47
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims description 31
- 125000005843 halogen group Chemical group 0.000 claims description 17
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 208000008589 Obesity Diseases 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 235000020824 obesity Nutrition 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- BPXYEYJNCXITEY-UHFFFAOYSA-N diazonio(trifluoromethoxy)azanide Chemical compound FC(F)(F)ON=[N+]=[N-] BPXYEYJNCXITEY-UHFFFAOYSA-N 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 4
- 201000008980 hyperinsulinism Diseases 0.000 claims description 4
- 210000004185 liver Anatomy 0.000 claims description 4
- 210000000056 organ Anatomy 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 3
- 208000031773 Insulin resistance syndrome Diseases 0.000 claims description 3
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 3
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 201000001421 hyperglycemia Diseases 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 201000008383 nephritis Diseases 0.000 claims description 3
- 230000002861 ventricular Effects 0.000 claims description 3
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 206010007556 Cardiac failure acute Diseases 0.000 claims description 2
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 2
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 2
- 208000006029 Cardiomegaly Diseases 0.000 claims description 2
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 206010052337 Diastolic dysfunction Diseases 0.000 claims description 2
- 206010048554 Endothelial dysfunction Diseases 0.000 claims description 2
- 208000009525 Myocarditis Diseases 0.000 claims description 2
- 208000001132 Osteoporosis Diseases 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 206010000891 acute myocardial infarction Diseases 0.000 claims description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000008694 endothelial dysfunction Effects 0.000 claims description 2
- 230000001969 hypertrophic effect Effects 0.000 claims description 2
- 208000017169 kidney disease Diseases 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 201000008827 tuberculosis Diseases 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- 206010049694 Left Ventricular Dysfunction Diseases 0.000 claims 1
- 206010042957 Systolic hypertension Diseases 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 222
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 116
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
- 239000000203 mixture Substances 0.000 description 98
- 238000002360 preparation method Methods 0.000 description 97
- 239000000243 solution Substances 0.000 description 92
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 87
- 239000007787 solid Substances 0.000 description 80
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 72
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
- 239000002904 solvent Substances 0.000 description 67
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
- 238000006243 chemical reaction Methods 0.000 description 61
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 46
- 235000019439 ethyl acetate Nutrition 0.000 description 44
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- 238000005481 NMR spectroscopy Methods 0.000 description 38
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 37
- 239000000047 product Substances 0.000 description 37
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 35
- 239000002585 base Substances 0.000 description 35
- 239000012044 organic layer Substances 0.000 description 35
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 34
- 239000000725 suspension Substances 0.000 description 34
- 238000005160 1H NMR spectroscopy Methods 0.000 description 32
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 32
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 30
- 239000000460 chlorine Substances 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 239000012043 crude product Substances 0.000 description 27
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 25
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 238000004809 thin layer chromatography Methods 0.000 description 24
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 23
- 239000011734 sodium Substances 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 20
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 20
- 239000003208 petroleum Substances 0.000 description 19
- 239000002244 precipitate Substances 0.000 description 19
- 238000006467 substitution reaction Methods 0.000 description 19
- 239000012267 brine Substances 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
- 239000008186 active pharmaceutical agent Substances 0.000 description 17
- 239000010410 layer Substances 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 239000002253 acid Substances 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- 229960000583 acetic acid Drugs 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 12
- 239000007821 HATU Substances 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 11
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 10
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- 239000013058 crude material Substances 0.000 description 10
- 108090000623 proteins and genes Proteins 0.000 description 10
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 239000004202 carbamide Substances 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 239000012505 Superdex™ Substances 0.000 description 7
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- 102000004169 proteins and genes Human genes 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
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- 206010022489 Insulin Resistance Diseases 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
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- 125000004429 atom Chemical group 0.000 description 6
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- 125000004356 hydroxy functional group Chemical group O* 0.000 description 6
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
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- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
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- DLHWBTWCGRIBQY-UHFFFAOYSA-N 4-(isoquinolin-3-ylamino)cyclohexan-1-one Chemical compound C1CC(=O)CCC1NC1=CC2=CC=CC=C2C=N1 DLHWBTWCGRIBQY-UHFFFAOYSA-N 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- DORUFFIEQPTNSP-HAQNSBGRSA-N C1C[C@@H](O)CC[C@@H]1NC1=NC=C(C=CC(F)=C2)C2=N1 Chemical compound C1C[C@@H](O)CC[C@@H]1NC1=NC=C(C=CC(F)=C2)C2=N1 DORUFFIEQPTNSP-HAQNSBGRSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
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- VYCKDIRCVDCQAE-UHFFFAOYSA-N isoquinolin-3-amine Chemical compound C1=CC=C2C=NC(N)=CC2=C1 VYCKDIRCVDCQAE-UHFFFAOYSA-N 0.000 description 5
- 239000012139 lysis buffer Substances 0.000 description 5
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- 238000002953 preparative HPLC Methods 0.000 description 5
- SRKXVESHUPPYMO-UHFFFAOYSA-N quinazoline-7-carboxylic acid Chemical compound C1=NC=NC2=CC(C(=O)O)=CC=C21 SRKXVESHUPPYMO-UHFFFAOYSA-N 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
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- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 4
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- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 4
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| US74608706P | 2006-05-01 | 2006-05-01 | |
| PCT/IB2007/001123 WO2007125405A2 (en) | 2006-05-01 | 2007-04-19 | Substituted 2-amino-fused heterocyclic compounds |
Publications (2)
| Publication Number | Publication Date |
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| JP2009535393A true JP2009535393A (ja) | 2009-10-01 |
| JP2009535393A5 JP2009535393A5 (enExample) | 2010-03-04 |
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| JP2009508525A Withdrawn JP2009535393A (ja) | 2006-05-01 | 2007-04-19 | 置換2−アミノ縮合複素環式化合物 |
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| US (2) | US7998978B2 (enExample) |
| EP (1) | EP2024342A2 (enExample) |
| JP (1) | JP2009535393A (enExample) |
| CA (1) | CA2651072A1 (enExample) |
| WO (1) | WO2007125405A2 (enExample) |
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| JP2013519701A (ja) * | 2010-02-17 | 2013-05-30 | エフ.ホフマン−ラ ロシュ アーゲー | ピペリジン誘導体 |
| JP2013523715A (ja) * | 2010-03-31 | 2013-06-17 | アクテリオン ファーマシューティカルズ リミテッド | イソキノリン−3−イル尿素誘導体 |
| JP2013527173A (ja) * | 2010-05-07 | 2013-06-27 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | アザインダゾール |
| JP2014521696A (ja) * | 2011-08-04 | 2014-08-28 | アレイ バイオファーマ、インコーポレイテッド | セリン/スレオニンキナーゼインヒビターとしてのキナゾリン化合物 |
| JP2014530897A (ja) * | 2011-10-28 | 2014-11-20 | アステックス、セラピューティックス、リミテッドAstex Therapeutics Limited | 新規化合物 |
| WO2015083833A1 (ja) * | 2013-12-06 | 2015-06-11 | カルナバイオサイエンス株式会社 | 新規キナゾリン誘導体 |
| JP2015524812A (ja) * | 2012-07-27 | 2015-08-27 | バイオジェン・エムエイ・インコーポレイテッドBiogen MA Inc. | Atx調節剤 |
| JP2015526519A (ja) * | 2012-08-27 | 2015-09-10 | アレイ バイオファーマ、インコーポレイテッド | 過剰増殖性│疾患の処置のためのセリン/スレオニンキナーゼ阻害剤 |
| JP2015529657A (ja) * | 2012-08-07 | 2015-10-08 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングMerck Patent Gesellschaft mit beschraenkter Haftung | プロテインキナーゼ阻害剤としてのピリドピリミジン誘導体 |
| CN109310690A (zh) * | 2016-04-27 | 2019-02-05 | 萨穆梅德有限公司 | 异喹啉-3-基甲酰胺类及其制备和其用途 |
| JP2019515931A (ja) * | 2016-04-27 | 2019-06-13 | サミュメッド リミテッド ライアビリティ カンパニー | イソキノリン−3イル−カルボキサミドならびにその調製および使用の方法 |
| JP2019517517A (ja) * | 2016-06-02 | 2019-06-24 | セルジーン コーポレイション | 動物及びヒトの抗マラリア薬 |
| JP2022501409A (ja) * | 2018-10-02 | 2022-01-06 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 癌の治療用のイソキノリン化合物 |
| JP2023002643A (ja) * | 2016-05-24 | 2023-01-10 | ジェネンテック, インコーポレイテッド | Cbp/ep300の複素環式インヒビターおよびがんの処置におけるそれらの使用 |
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| US3535321A (en) * | 1967-12-01 | 1970-10-20 | Smithkline Corp | 2-carbalkoxyaminodihydroquinazolines |
| ATE309241T1 (de) * | 1999-09-10 | 2005-11-15 | Merck & Co Inc | Tyrosin kinase inhibitoren |
| DE10021246A1 (de) | 2000-04-25 | 2001-10-31 | Schering Ag | Substituierte Benzoesäureamide und deren Verwendung als Arzneimittel |
| ES2292753T4 (es) | 2001-03-29 | 2009-02-16 | Vertex Pharmaceuticals Incorporated | Inhibidores de quinasas n-terminales c-jun (jnk) y otras proteina quinasas. |
| MXPA05007503A (es) | 2003-01-17 | 2005-09-21 | Warner Lambert Co | Heterociclicos 2-aminopiridina sustituidos como inhibidores de proliferacion celular. |
| DE602006008945D1 (de) | 2005-06-28 | 2009-10-15 | Sanofi Aventis | Isochinolinderivate als inhibitoren von rho-kinase |
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- 2007-04-19 JP JP2009508525A patent/JP2009535393A/ja not_active Withdrawn
- 2007-04-19 WO PCT/IB2007/001123 patent/WO2007125405A2/en not_active Ceased
- 2007-04-19 CA CA002651072A patent/CA2651072A1/en not_active Abandoned
- 2007-04-19 EP EP07734441A patent/EP2024342A2/en not_active Withdrawn
- 2007-04-19 US US12/299,381 patent/US7998978B2/en not_active Expired - Fee Related
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- 2011-08-08 US US13/204,741 patent/US20120035194A1/en not_active Abandoned
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Also Published As
| Publication number | Publication date |
|---|---|
| US7998978B2 (en) | 2011-08-16 |
| US20120035194A1 (en) | 2012-02-09 |
| EP2024342A2 (en) | 2009-02-18 |
| US20100056506A1 (en) | 2010-03-04 |
| CA2651072A1 (en) | 2007-11-08 |
| WO2007125405A2 (en) | 2007-11-08 |
| WO2007125405A3 (en) | 2008-01-17 |
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