KR20150041647A - 치환된 헤테로-아제핀온 - Google Patents

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Publication number

KR20150041647A

KR20150041647A KR20157005929A KR20157005929A KR20150041647A KR 20150041647 A KR20150041647 A KR 20150041647A KR 20157005929 A KR20157005929 A KR 20157005929A KR 20157005929 A KR20157005929 A KR 20157005929A KR 20150041647 A KR20150041647 A KR 20150041647A

Authority

KR

South Korea

Prior art keywords

alkyl

methyl

oxo

methylamino

aryl

Prior art date

2012-08-09

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.)

Withdrawn

Links

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• 150000001875 compounds Chemical class 0.000 claims abstract description 280
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 21
• 201000011510 cancer Diseases 0.000 claims abstract description 18
• 238000011282 treatment Methods 0.000 claims abstract description 17
• -1 C 1 -6 - alkyl Chemical group 0.000 claims description 875
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 213
• 125000003118 aryl group Chemical group 0.000 claims description 198
• 125000005605 benzo group Chemical group 0.000 claims description 174
• 229910052739 hydrogen Inorganic materials 0.000 claims description 157
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 126
• 229910052799 carbon Inorganic materials 0.000 claims description 105
• 238000000034 method Methods 0.000 claims description 95
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 75
• 125000000217 alkyl group Chemical group 0.000 claims description 73
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 58
• 229910052801 chlorine Inorganic materials 0.000 claims description 56
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 55
• 229910052794 bromium Inorganic materials 0.000 claims description 55
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 55
• 125000001072 heteroaryl group Chemical group 0.000 claims description 55
• 229910052731 fluorine Inorganic materials 0.000 claims description 54
• 125000002252 acyl group Chemical group 0.000 claims description 53
• 229910005965 SO 2 Inorganic materials 0.000 claims description 50
• 125000000623 heterocyclic group Chemical group 0.000 claims description 48
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 47
• 150000003839 salts Chemical class 0.000 claims description 40
• 125000003003 spiro group Chemical group 0.000 claims description 40
• SOWBFZRMHSNYGE-UHFFFAOYSA-N Monoamide-Oxalic acid Natural products NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 claims description 39
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 36
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 32
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 29
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 27
• 238000002360 preparation method Methods 0.000 claims description 26
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 25
• 229910052760 oxygen Inorganic materials 0.000 claims description 24
• 239000001257 hydrogen Substances 0.000 claims description 23
• 229910052717 sulfur Inorganic materials 0.000 claims description 23
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 21
• 229910052757 nitrogen Inorganic materials 0.000 claims description 18
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
• 125000003545 alkoxy group Chemical group 0.000 claims description 15
• 150000002431 hydrogen Chemical class 0.000 claims description 14
• 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 13
• 125000001424 substituent group Chemical group 0.000 claims description 13
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 11
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 10
• VHWJSJBTUWUEAL-UHFFFAOYSA-N propanamide;hydrochloride Chemical compound Cl.CCC(N)=O VHWJSJBTUWUEAL-UHFFFAOYSA-N 0.000 claims description 8
• 229940080818 propionamide Drugs 0.000 claims description 8
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 7
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 7
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 6
• HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical group C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 claims description 6
• 125000004043 oxo group Chemical group O=* 0.000 claims description 6
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
• BMBANPOHPFKVTA-UHFFFAOYSA-N benzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=O)C1=CC=CC=C1 BMBANPOHPFKVTA-UHFFFAOYSA-N 0.000 claims description 5
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 230000002265 prevention Effects 0.000 claims description 5
• ZSZBVCQVYPCNIF-UHFFFAOYSA-N propanamide;2,2,2-trifluoroacetic acid Chemical compound CCC(N)=O.OC(=O)C(F)(F)F ZSZBVCQVYPCNIF-UHFFFAOYSA-N 0.000 claims description 5
• 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 claims description 5
• RWTGSAXSZXQBRM-MBSDFSHPSA-N (2s)-2-(methylamino)-n-[(3s)-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-4,5-dihydro-3h-1-benzazepin-3-yl]propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)CCC2=CC=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 RWTGSAXSZXQBRM-MBSDFSHPSA-N 0.000 claims description 4
• XQHYGDOJDYACHI-HBYWCBEISA-N (2s)-n-(5-benzyl-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl)-2-(methylamino)propanamide;hydrochloride Chemical compound Cl.O=C1C(NC(=O)[C@H](C)NC)CSC2=CC=CC=C2N1CC1=CC=CC=C1 XQHYGDOJDYACHI-HBYWCBEISA-N 0.000 claims description 4
• RRRZHUQUSBVQNZ-QNNMEKCMSA-N (2s)-n-[(3r)-9-amino-5-(naphthalen-1-ylmethyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl]-2-(methylamino)propanamide;hydrochloride Chemical compound Cl.O=C1[C@@H](NC(=O)[C@H](C)NC)CSC2=C(N)C=CC=C2N1CC1=CC=CC2=CC=CC=C12 RRRZHUQUSBVQNZ-QNNMEKCMSA-N 0.000 claims description 4
• 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 4
• 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 4
• WAKRDDXHAXBEQA-UHFFFAOYSA-N benzoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C1=CC=CC=C1 WAKRDDXHAXBEQA-UHFFFAOYSA-N 0.000 claims description 4
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
• NSIMSTVWDYAFBY-QDMMYLPHSA-N n-[(3r)-3-[[(2s)-2-(methylamino)propanoyl]amino]-5-(naphthalen-1-ylmethyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-9-yl]benzamide;hydrochloride Chemical compound Cl.C([C@@H](C(N(CC=1C2=CC=CC=C2C=CC=1)C1=CC=C2)=O)NC(=O)[C@H](C)NC)SC1=C2NC(=O)C1=CC=CC=C1 NSIMSTVWDYAFBY-QDMMYLPHSA-N 0.000 claims description 4
• 229930192474 thiophene Natural products 0.000 claims description 4
• PYGNINGYNZYWBV-GUTACTQSSA-N (2s)-n-[(3s)-5-[(6-bromo-2-methoxynaphthalen-1-yl)methyl]-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-2-(methylamino)butanamide;hydrochloride Chemical compound Cl.O=C1[C@@H](NC(=O)[C@@H](NC)CC)COC2=CC=CC=C2N1CC1=C(OC)C=CC2=CC(Br)=CC=C12 PYGNINGYNZYWBV-GUTACTQSSA-N 0.000 claims description 3
• HCSLWAKAKAIBTE-ZOEDVAEJSA-N (2s)-n-[(3s)-5-[(7-bromo-3-methoxynaphthalen-2-yl)methyl]-8-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-2-(methylamino)propanamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1[C@@H](NC(=O)[C@H](C)NC)COC2=CC(C)=CC=C2N1CC1=CC2=CC(Br)=CC=C2C=C1OC HCSLWAKAKAIBTE-ZOEDVAEJSA-N 0.000 claims description 3
• RCQFDAMHGMCSFG-UHFFFAOYSA-N 2-(4-methylindol-1-yl)benzonitrile Chemical compound C1=CC=2C(C)=CC=CC=2N1C1=CC=CC=C1C#N RCQFDAMHGMCSFG-UHFFFAOYSA-N 0.000 claims description 3
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 3
• 150000001408 amides Chemical class 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 125000006431 methyl cyclopropyl group Chemical group 0.000 claims description 3
• 239000001294 propane Substances 0.000 claims description 3
• 239000004480 active ingredient Substances 0.000 claims description 2
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 33
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 10
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims 8
• CNHCWOHOXAYULJ-UHFFFAOYSA-N n'-methylpropanehydrazide;hydrochloride Chemical compound Cl.CCC(=O)NNC CNHCWOHOXAYULJ-UHFFFAOYSA-N 0.000 claims 1
• 238000011321 prophylaxis Methods 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
• 201000010099 disease Diseases 0.000 abstract description 4
• 230000002062 proliferating effect Effects 0.000 abstract description 3
• 239000000203 mixture Substances 0.000 description 336
• 239000000243 solution Substances 0.000 description 220
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 214
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 107
• 235000019439 ethyl acetate Nutrition 0.000 description 107
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 105
• 239000011734 sodium Substances 0.000 description 100
• 239000007787 solid Substances 0.000 description 100
• 239000000284 extract Substances 0.000 description 81
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 71
• 239000012267 brine Substances 0.000 description 70
• 238000000746 purification Methods 0.000 description 63
• 125000005843 halogen group Chemical group 0.000 description 58
• 238000006243 chemical reaction Methods 0.000 description 57
• GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 50
• 238000010898 silica gel chromatography Methods 0.000 description 50
• 239000006260 foam Substances 0.000 description 48
• 229920006395 saturated elastomer Polymers 0.000 description 48
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
• KNTZCGBYFGEMFR-UHFFFAOYSA-N (propan-2-ylazaniumyl)formate Chemical compound CC(C)NC(O)=O KNTZCGBYFGEMFR-UHFFFAOYSA-N 0.000 description 39
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 38
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 38
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
• 239000000706 filtrate Substances 0.000 description 35
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 31
• YTKNRNVTHYZZEE-UHFFFAOYSA-N oxazepin-3-ylcarbamic acid Chemical compound C1=CC(=NOC=C1)NC(=O)O YTKNRNVTHYZZEE-UHFFFAOYSA-N 0.000 description 30
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
• RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 description 27
• 125000006239 protecting group Chemical group 0.000 description 27
• 238000012746 preparative thin layer chromatography Methods 0.000 description 25
• 238000003756 stirring Methods 0.000 description 25
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 24
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 23
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 22
• 239000000463 material Substances 0.000 description 21
• 239000000047 product Substances 0.000 description 21
• 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 21
• 230000002829 reductive effect Effects 0.000 description 20
• 238000003818 flash chromatography Methods 0.000 description 19
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 18
• 239000002904 solvent Substances 0.000 description 18
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 17
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 17
• 108091007065 BIRCs Proteins 0.000 description 17
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 16
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• 239000012230 colorless oil Substances 0.000 description 15
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
• 102000055031 Inhibitor of Apoptosis Proteins Human genes 0.000 description 14
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 14
• 239000003921 oil Substances 0.000 description 14
• 235000019260 propionic acid Nutrition 0.000 description 14
• TUMCWFMHZOUPDA-UHFFFAOYSA-N 2-ethylsulfanyl-1,3-benzothiazol-6-amine Chemical compound C1=C(N)C=C2SC(SCC)=NC2=C1 TUMCWFMHZOUPDA-UHFFFAOYSA-N 0.000 description 13
• 101100111638 Arabidopsis thaliana BIR2 gene Proteins 0.000 description 13
• 239000011541 reaction mixture Substances 0.000 description 13
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
• BWIOURVJVDKDOC-UHFFFAOYSA-N 6-bromo-1-(chloromethyl)-2-methoxynaphthalene Chemical compound C1=C(Br)C=CC2=C(CCl)C(OC)=CC=C21 BWIOURVJVDKDOC-UHFFFAOYSA-N 0.000 description 12
• 108700031544 X-Linked Inhibitor of Apoptosis Proteins 0.000 description 12
• 102000050257 X-Linked Inhibitor of Apoptosis Human genes 0.000 description 12
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 12
• 229910000104 sodium hydride Inorganic materials 0.000 description 12
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
• SFJGCXYXEFWEBK-UHFFFAOYSA-N oxazepine Chemical compound O1C=CC=CC=N1 SFJGCXYXEFWEBK-UHFFFAOYSA-N 0.000 description 11
• 239000000843 powder Substances 0.000 description 11
• 238000003786 synthesis reaction Methods 0.000 description 11
• VLHQXRIIQSTJCQ-LURJTMIESA-N (2s)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoic acid Chemical compound OC(=O)[C@H](C)N(C)C(=O)OC(C)(C)C VLHQXRIIQSTJCQ-LURJTMIESA-N 0.000 description 10
• ULBSGKVZMMVYGE-UHFFFAOYSA-N FC(C(=O)O)(F)F.O1N=CC(CC=C1)=O Chemical compound FC(C(=O)O)(F)F.O1N=CC(CC=C1)=O ULBSGKVZMMVYGE-UHFFFAOYSA-N 0.000 description 10
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
• QCIGLPLDNRDLQQ-UHFFFAOYSA-N butan-2-ylcarbamic acid Chemical compound CCC(C)NC(O)=O QCIGLPLDNRDLQQ-UHFFFAOYSA-N 0.000 description 10
• 125000004432 carbon atom Chemical group C* 0.000 description 10
• 239000003153 chemical reaction reagent Substances 0.000 description 10
• 239000002480 mineral oil Substances 0.000 description 10
• 235000010446 mineral oil Nutrition 0.000 description 10
• 239000012044 organic layer Substances 0.000 description 10
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 9
• 102000011727 Caspases Human genes 0.000 description 9
• 108010076667 Caspases Proteins 0.000 description 9
• 210000004027 cell Anatomy 0.000 description 9
• 239000013078 crystal Substances 0.000 description 9
• 238000010438 heat treatment Methods 0.000 description 9
• 229910052763 palladium Inorganic materials 0.000 description 9
• 239000002244 precipitate Substances 0.000 description 9
• 108090000765 processed proteins & peptides Proteins 0.000 description 9
• 230000006907 apoptotic process Effects 0.000 description 8
• 239000003054 catalyst Substances 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 7
• 125000003342 alkenyl group Chemical group 0.000 description 7
• 125000005997 bromomethyl group Chemical group 0.000 description 7
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 7
• 238000000227 grinding Methods 0.000 description 7
• 239000010410 layer Substances 0.000 description 7
• PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 6
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