NO312457B1 - Alkyloksyaminosubstituerte fluorenoner - Google Patents
Alkyloksyaminosubstituerte fluorenoner Download PDFInfo
- Publication number
- NO312457B1 NO312457B1 NO19985577A NO985577A NO312457B1 NO 312457 B1 NO312457 B1 NO 312457B1 NO 19985577 A NO19985577 A NO 19985577A NO 985577 A NO985577 A NO 985577A NO 312457 B1 NO312457 B1 NO 312457B1
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- mol
- methoxy
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- 150000008376 fluorenones Chemical class 0.000 title description 11
- 150000001875 compounds Chemical class 0.000 claims description 157
- -1 methoxy, ethoxy, n-propoxy, butoxy Chemical group 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 6
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 5
- 239000005977 Ethylene Substances 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 140
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 138
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 127
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 118
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 118
- 238000006243 chemical reaction Methods 0.000 description 109
- 239000000243 solution Substances 0.000 description 108
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 84
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 84
- 238000003756 stirring Methods 0.000 description 78
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 76
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
- 239000007787 solid Substances 0.000 description 60
- 229910001868 water Inorganic materials 0.000 description 60
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 59
- 235000019439 ethyl acetate Nutrition 0.000 description 57
- 239000000203 mixture Substances 0.000 description 57
- 102000003923 Protein Kinase C Human genes 0.000 description 50
- 108090000315 Protein Kinase C Proteins 0.000 description 50
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 50
- 239000000284 extract Substances 0.000 description 44
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 39
- 239000011541 reaction mixture Substances 0.000 description 39
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 38
- 235000019341 magnesium sulphate Nutrition 0.000 description 38
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- 229910052786 argon Inorganic materials 0.000 description 35
- 239000000460 chlorine Substances 0.000 description 34
- 238000010992 reflux Methods 0.000 description 34
- 239000002904 solvent Substances 0.000 description 34
- 239000012267 brine Substances 0.000 description 32
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 31
- 239000003921 oil Substances 0.000 description 30
- 235000019198 oils Nutrition 0.000 description 30
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 25
- 238000000034 method Methods 0.000 description 25
- 239000002253 acid Substances 0.000 description 24
- 239000012141 concentrate Substances 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- 238000004458 analytical method Methods 0.000 description 23
- 239000012044 organic layer Substances 0.000 description 23
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 22
- 201000010099 disease Diseases 0.000 description 21
- 239000000706 filtrate Substances 0.000 description 21
- YLQWCDOCJODRMT-UHFFFAOYSA-N fluoren-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C2=C1 YLQWCDOCJODRMT-UHFFFAOYSA-N 0.000 description 21
- 239000007788 liquid Substances 0.000 description 21
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 20
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 20
- 239000010410 layer Substances 0.000 description 20
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 19
- 235000008504 concentrate Nutrition 0.000 description 19
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 19
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 16
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 239000012458 free base Substances 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- 238000010791 quenching Methods 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 13
- 206010028980 Neoplasm Diseases 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 235000010290 biphenyl Nutrition 0.000 description 13
- 239000003112 inhibitor Substances 0.000 description 13
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 13
- 239000011777 magnesium Substances 0.000 description 13
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- 239000011343 solid material Substances 0.000 description 12
- 238000001914 filtration Methods 0.000 description 11
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 10
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 10
- 230000004913 activation Effects 0.000 description 10
- 239000004305 biphenyl Substances 0.000 description 10
- 150000003857 carboxamides Chemical class 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 238000001704 evaporation Methods 0.000 description 10
- 230000008020 evaporation Effects 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- 235000011181 potassium carbonates Nutrition 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 9
- 150000001408 amides Chemical class 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 229910052749 magnesium Inorganic materials 0.000 description 9
- 150000004702 methyl esters Chemical class 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- XTPXSGADBUIAKJ-UHFFFAOYSA-N 2,4-dimethoxy-4,5-dihydro-1,3-oxazole Chemical compound COC1COC(OC)=N1 XTPXSGADBUIAKJ-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 8
- 230000001613 neoplastic effect Effects 0.000 description 8
- 239000012047 saturated solution Substances 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- MXRROKOQJXMIQQ-UHFFFAOYSA-N 2,5-dimethoxyfluoren-9-one Chemical compound C1=CC(OC)=C2C3=CC=C(OC)C=C3C(=O)C2=C1 MXRROKOQJXMIQQ-UHFFFAOYSA-N 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 102000001253 Protein Kinase Human genes 0.000 description 7
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 238000005804 alkylation reaction Methods 0.000 description 7
- 239000012300 argon atmosphere Substances 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 108060006633 protein kinase Proteins 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 235000011150 stannous chloride Nutrition 0.000 description 7
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 6
- BNLICISMBGNGFN-UHFFFAOYSA-N 2,5-dihydroxy-4-methoxyfluoren-9-one Chemical compound O=C1C2=CC=CC(O)=C2C2=C1C=C(O)C=C2OC BNLICISMBGNGFN-UHFFFAOYSA-N 0.000 description 6
- YMDNODNLFSHHCV-UHFFFAOYSA-N 2-chloro-n,n-diethylethanamine Chemical compound CCN(CC)CCCl YMDNODNLFSHHCV-UHFFFAOYSA-N 0.000 description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000007983 Tris buffer Substances 0.000 description 6
- 230000029936 alkylation Effects 0.000 description 6
- 150000001543 aryl boronic acids Chemical class 0.000 description 6
- 150000004074 biphenyls Chemical class 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 229940043279 diisopropylamine Drugs 0.000 description 6
- 239000008188 pellet Substances 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 239000001119 stannous chloride Substances 0.000 description 6
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 6
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- RAGSWDIQBBZLLL-UHFFFAOYSA-N 2-chloroethyl(diethyl)azanium;chloride Chemical compound Cl.CCN(CC)CCCl RAGSWDIQBBZLLL-UHFFFAOYSA-N 0.000 description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 5
- BYKIWGLHOZPGDM-UHFFFAOYSA-N 5-hydroxy-4-methoxy-2-propoxyfluoren-9-one Chemical compound O=C1C2=CC=CC(O)=C2C2=C1C=C(OCCC)C=C2OC BYKIWGLHOZPGDM-UHFFFAOYSA-N 0.000 description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 5
- 239000007818 Grignard reagent Substances 0.000 description 5
- 230000002159 abnormal effect Effects 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000020335 dealkylation Effects 0.000 description 5
- 238000006900 dealkylation reaction Methods 0.000 description 5
- KXKLIIDALHFICZ-UHFFFAOYSA-N dengibsin Natural products COc1cc(O)c2c(c1)C(=O)c3c(O)cccc23 KXKLIIDALHFICZ-UHFFFAOYSA-N 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 150000004795 grignard reagents Chemical class 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- YERKTUFRISJBOQ-UHFFFAOYSA-N 1-bromo-2-methoxy-4-propan-2-yloxybenzene Chemical compound COC1=CC(OC(C)C)=CC=C1Br YERKTUFRISJBOQ-UHFFFAOYSA-N 0.000 description 4
- FODBVCSYJKNBLO-UHFFFAOYSA-N 2,3-dimethoxybenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1OC FODBVCSYJKNBLO-UHFFFAOYSA-N 0.000 description 4
- FJEHTZGPOWPYTC-UHFFFAOYSA-N 2,5-dihydroxyfluoren-9-one Chemical compound C1=CC(O)=C2C3=CC=C(O)C=C3C(=O)C2=C1 FJEHTZGPOWPYTC-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
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- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 4
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- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
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- 239000007858 starting material Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
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- 238000004809 thin layer chromatography Methods 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- PBKONEOXTCPAFI-UHFFFAOYSA-N 1,2,4-trichlorobenzene Chemical compound ClC1=CC=C(Cl)C(Cl)=C1 PBKONEOXTCPAFI-UHFFFAOYSA-N 0.000 description 3
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 3
- XKZQKPRCPNGNFR-UHFFFAOYSA-N 2-(3-hydroxyphenyl)phenol Chemical compound OC1=CC=CC(C=2C(=CC=CC=2)O)=C1 XKZQKPRCPNGNFR-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
- C07C217/14—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring
- C07C217/24—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system containing rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US65558496A | 1996-05-30 | 1996-05-30 | |
US65553796A | 1996-05-30 | 1996-05-30 | |
PCT/US1997/006602 WO1997045397A1 (en) | 1996-05-30 | 1997-04-24 | Alkyloxyamino substituted fluorenones and their use as protein kinase c inhibitors |
Publications (3)
Publication Number | Publication Date |
---|---|
NO985577D0 NO985577D0 (no) | 1998-11-27 |
NO985577L NO985577L (no) | 1999-01-27 |
NO312457B1 true NO312457B1 (no) | 2002-05-13 |
Family
ID=27096988
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19985577A NO312457B1 (no) | 1996-05-30 | 1998-11-27 | Alkyloksyaminosubstituerte fluorenoner |
Country Status (18)
Country | Link |
---|---|
EP (1) | EP0906268B1 (xx) |
JP (1) | JP3897363B2 (xx) |
CN (1) | CN1160309C (xx) |
AR (1) | AR008375A1 (xx) |
AT (1) | ATE209626T1 (xx) |
AU (1) | AU737073B2 (xx) |
BR (1) | BR9709406B1 (xx) |
CA (1) | CA2257136C (xx) |
DE (1) | DE69708629T2 (xx) |
DK (1) | DK0906268T3 (xx) |
ES (1) | ES2170390T3 (xx) |
HK (1) | HK1019147A1 (xx) |
HU (1) | HUP9901621A3 (xx) |
IL (1) | IL126873A (xx) |
NO (1) | NO312457B1 (xx) |
NZ (1) | NZ332597A (xx) |
PT (1) | PT906268E (xx) |
WO (1) | WO1997045397A1 (xx) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6103712A (en) * | 1998-03-05 | 2000-08-15 | Eli Lilly And Company | Therapeutic treatment for asthma |
US6103713A (en) * | 1998-03-05 | 2000-08-15 | Eli Lilly And Company | Therapeutic treatment for autoimmune diseases |
DE19908504C2 (de) * | 1999-02-26 | 2003-04-30 | Boehringer Ingelheim Pharma | Großtechnisches Verfahren zur Herstellung von Derivaten der Biphenyl-2-carbonsäure durch Verseifen eines (2-Oxazolinyl)-2-biphenyl-Derivats mit Salzsäure |
DE19917990A1 (de) * | 1999-04-20 | 2000-11-02 | Florian Lang | Arzneimittel enthaltend Hemmstoffe der zellvolumenregulierten humanen Kinase h-sgk |
BR0113258A (pt) | 2000-08-18 | 2003-07-15 | Agouron Pharma | Compostos, pró-drogas, metabólitos ou sais, métodos de tratamento de condição doentia em mamìferos, mediada pela atividade de proteìna cinase e métodos de modulação ou inibição da atividade de um receptor de proteìna cinase |
US20050171079A1 (en) * | 2004-02-04 | 2005-08-04 | Schrimpf Michael R. | Amino-substituted tricyclic derivatives and methods of use |
US7365193B2 (en) | 2004-02-04 | 2008-04-29 | Abbott Laboratories | Amino-substituted tricyclic derivatives and methods of use |
CA2789972A1 (en) * | 2010-01-11 | 2011-07-14 | Healor Ltd. | Method for treatment of inflammatory disease and disorder |
CN103204781B (zh) * | 2013-03-14 | 2015-04-01 | 武汉大学 | 2,7–二取代芴酮衍生物及其制备方法与应用 |
CN109053435A (zh) * | 2018-08-03 | 2018-12-21 | 上海华堇生物技术有限责任公司 | 2,3-二甲氧基苯甲酰氯的制备方法 |
CN115590964A (zh) * | 2022-09-14 | 2023-01-13 | 苏州大学(Cn) | 蛋白激酶c抑制剂在制备抗肿瘤转移药物中的应用 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL33573A (en) * | 1968-12-30 | 1973-10-25 | Richardson Merrell Inc | Bis-basic ethers and thioethers of fluorenone,fluorenol and fluorene |
US5034384A (en) * | 1990-08-01 | 1991-07-23 | Merck & Co., Inc. | 2-(9-fluorenonyl)-carbapenem antibacterial agents |
-
1997
- 1997-04-24 JP JP54237197A patent/JP3897363B2/ja not_active Expired - Fee Related
- 1997-04-24 NZ NZ332597A patent/NZ332597A/xx not_active IP Right Cessation
- 1997-04-24 PT PT97921288T patent/PT906268E/pt unknown
- 1997-04-24 AT AT97921288T patent/ATE209626T1/de active
- 1997-04-24 EP EP97921288A patent/EP0906268B1/en not_active Expired - Lifetime
- 1997-04-24 DE DE69708629T patent/DE69708629T2/de not_active Expired - Lifetime
- 1997-04-24 HU HU9901621A patent/HUP9901621A3/hu unknown
- 1997-04-24 ES ES97921288T patent/ES2170390T3/es not_active Expired - Lifetime
- 1997-04-24 IL IL12687397A patent/IL126873A/xx not_active IP Right Cessation
- 1997-04-24 AU AU27365/97A patent/AU737073B2/en not_active Ceased
- 1997-04-24 WO PCT/US1997/006602 patent/WO1997045397A1/en active IP Right Grant
- 1997-04-24 DK DK97921288T patent/DK0906268T3/da active
- 1997-04-24 BR BRPI9709406-4A patent/BR9709406B1/pt not_active IP Right Cessation
- 1997-04-24 CA CA002257136A patent/CA2257136C/en not_active Expired - Fee Related
- 1997-04-24 CN CNB971951411A patent/CN1160309C/zh not_active Expired - Fee Related
- 1997-05-28 AR ARP970102266A patent/AR008375A1/es active IP Right Grant
-
1998
- 1998-11-27 NO NO19985577A patent/NO312457B1/no not_active IP Right Cessation
-
1999
- 1999-10-05 HK HK99104317A patent/HK1019147A1/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
CA2257136C (en) | 2004-07-20 |
DE69708629T2 (de) | 2002-08-01 |
CN1220660A (zh) | 1999-06-23 |
HK1019147A1 (en) | 2000-01-14 |
BR9709406B1 (pt) | 2009-05-05 |
CA2257136A1 (en) | 1997-12-04 |
AU2736597A (en) | 1998-01-05 |
CN1160309C (zh) | 2004-08-04 |
WO1997045397A1 (en) | 1997-12-04 |
IL126873A0 (en) | 1999-09-22 |
ATE209626T1 (de) | 2001-12-15 |
ES2170390T3 (es) | 2002-08-01 |
NO985577D0 (no) | 1998-11-27 |
DE69708629D1 (de) | 2002-01-10 |
HUP9901621A3 (en) | 2002-01-28 |
EP0906268B1 (en) | 2001-11-28 |
PT906268E (pt) | 2002-05-31 |
NZ332597A (en) | 2000-08-25 |
JP3897363B2 (ja) | 2007-03-22 |
JP2000511528A (ja) | 2000-09-05 |
AR008375A1 (es) | 2000-01-19 |
NO985577L (no) | 1999-01-27 |
EP0906268A1 (en) | 1999-04-07 |
IL126873A (en) | 2005-09-25 |
HUP9901621A2 (hu) | 1999-08-30 |
AU737073B2 (en) | 2001-08-09 |
BR9709406A (pt) | 1999-08-10 |
DK0906268T3 (da) | 2002-03-18 |
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