NO312457B1 - Alkyloksyaminosubstituerte fluorenoner - Google Patents

Alkyloksyaminosubstituerte fluorenoner Download PDF

Info

Publication number: NO312457B1
Authority: NO; Norway
Prior art keywords: mmol; mol; methoxy; reaction; give
Prior art date: 1996-05-30

Application number

NO19985577A

Other languages

English (en)

Norwegian (no)

Other versions

NO985577L (no

NO985577D0 (no

Inventor

Winton Dennis Jones

Fred Lawrence Ciske

Robert Joseph Dinerstein

Keith Allen Diekema

Original Assignee

Aventis Pharma Inc

Priority date (The priority date 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 date listed.)

1996-05-30

Filing date

1998-11-27

Publication date

2002-05-13

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27096988&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO312457(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1998-11-27 Application filed by Aventis Pharma Inc filed Critical Aventis Pharma Inc

1998-11-27 Publication of NO985577D0 publication Critical patent/NO985577D0/no

1999-01-27 Publication of NO985577L publication Critical patent/NO985577L/no

2002-05-13 Publication of NO312457B1 publication Critical patent/NO312457B1/no

Links

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
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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
UYDZUCNMZXCLJI-UHFFFAOYSA-N 4-bromo-3-methoxyphenol Chemical compound COC1=CC(O)=CC=C1Br UYDZUCNMZXCLJI-UHFFFAOYSA-N 0.000 description 4
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
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
206010020772 Hypertension Diseases 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
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OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 4
208000035269 cancer or benign tumor Diseases 0.000 description 4
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150000002367 halogens Chemical class 0.000 description 4
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230000005764 inhibitory process Effects 0.000 description 4
210000004072 lung Anatomy 0.000 description 4
238000006396 nitration reaction Methods 0.000 description 4
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
235000018102 proteins Nutrition 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
239000005720 sucrose Substances 0.000 description 4
239000006228 supernatant Substances 0.000 description 4
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

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- 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)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Pulmonology (AREA)
Diabetes (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Hematology (AREA)
Dermatology (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)

NO19985577A 1996-05-30 1998-11-27 Alkyloksyaminosubstituerte fluorenoner NO312457B1 (no)

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 (pt)
JP (1)	JP3897363B2 (pt)
CN (1)	CN1160309C (pt)
AR (1)	AR008375A1 (pt)
AT (1)	ATE209626T1 (pt)
AU (1)	AU737073B2 (pt)
BR (1)	BR9709406B1 (pt)
CA (1)	CA2257136C (pt)
DE (1)	DE69708629T2 (pt)
DK (1)	DK0906268T3 (pt)
ES (1)	ES2170390T3 (pt)
HK (1)	HK1019147A1 (pt)
HU (1)	HUP9901621A3 (pt)
IL (1)	IL126873A (pt)
NO (1)	NO312457B1 (pt)
NZ (1)	NZ332597A (pt)
PT (1)	PT906268E (pt)
WO (1)	WO1997045397A1 (pt)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
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
ATE295354T1 (de) *	2000-08-18	2005-05-15	Agouron Pharma	Heterozyklische-hydroximino-fluorene und ihre verwendung zur inhibierung von proteinkinasen
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
EP2523677A2 (en) *	2010-01-11	2012-11-21	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

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* Cited by examiner, † Cited by third party
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 EP EP97921288A patent/EP0906268B1/en not_active Expired - Lifetime
- 1997-04-24 PT PT97921288T patent/PT906268E/pt unknown
- 1997-04-24 AT AT97921288T patent/ATE209626T1/de active
- 1997-04-24 AU AU27365/97A patent/AU737073B2/en not_active Ceased
- 1997-04-24 DK DK97921288T patent/DK0906268T3/da active
- 1997-04-24 JP JP54237197A patent/JP3897363B2/ja not_active Expired - Fee Related
- 1997-04-24 WO PCT/US1997/006602 patent/WO1997045397A1/en active IP Right Grant
- 1997-04-24 NZ NZ332597A patent/NZ332597A/xx not_active IP Right Cessation
- 1997-04-24 IL IL12687397A patent/IL126873A/xx not_active IP Right Cessation
- 1997-04-24 BR BRPI9709406-4A patent/BR9709406B1/pt not_active IP Right Cessation
- 1997-04-24 ES ES97921288T patent/ES2170390T3/es not_active Expired - Lifetime
- 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
- 1997-04-24 HU HU9901621A patent/HUP9901621A3/hu unknown
- 1997-04-24 DE DE69708629T patent/DE69708629T2/de not_active Expired - Lifetime
- 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
ATE209626T1 (de)	2001-12-15
HK1019147A1 (en)	2000-01-14
PT906268E (pt)	2002-05-31
DE69708629T2 (de)	2002-08-01
JP3897363B2 (ja)	2007-03-22
EP0906268A1 (en)	1999-04-07
IL126873A0 (en)	1999-09-22
CA2257136A1 (en)	1997-12-04
AU737073B2 (en)	2001-08-09
BR9709406A (pt)	1999-08-10
DK0906268T3 (da)	2002-03-18
EP0906268B1 (en)	2001-11-28
HUP9901621A3 (en)	2002-01-28
CN1160309C (zh)	2004-08-04
JP2000511528A (ja)	2000-09-05
CA2257136C (en)	2004-07-20
NZ332597A (en)	2000-08-25
HUP9901621A2 (hu)	1999-08-30
NO985577L (no)	1999-01-27
CN1220660A (zh)	1999-06-23
NO985577D0 (no)	1998-11-27
BR9709406B1 (pt)	2009-05-05
DE69708629D1 (de)	2002-01-10
IL126873A (en)	2005-09-25
WO1997045397A1 (en)	1997-12-04
AU2736597A (en)	1998-01-05
AR008375A1 (es)	2000-01-19
ES2170390T3 (es)	2002-08-01

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Date	Code	Title	Description
2013-12-02	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
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US7345068B2 (en)	2008-03-18	Aromatic amino acid derivatives and medicinal compositions
US5462954A (en)	1995-10-31	Substituted phenyl phenol leukotriene antagonists
JPH0684365B2 (ja)	1994-10-26	鎮吐剤または抗精神病剤として有用なベンゾフランカルボキサミド類
TW200424152A (en)	2004-11-16	Certain phenylacetic acids and derivatives
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NO312457B1 (no)	2002-05-13	Alkyloksyaminosubstituerte fluorenoner
CS360891A3 (en)	1992-06-17	Aryl derivatives
EP0728128A1 (en)	1996-08-28	Substituted phenyl compounds
EP0888327B1 (en)	2002-06-12	Benzopyran derivatives having leukotriene-antagonistic action
US5175173A (en)	1992-12-29	Carboxamides useful as antiemetic or antipsychotic agents
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Niu et al.	2015	Synthesis and bioactivity of new chalcone derivatives as potential tyrosinase activator based on the click chemistry
NO174345B (no)	1994-01-10	Analogifremgangsmaate for fremstilling av terapeutisk aktive indol-,benzofuran- og benzotiofenderivater
EA028303B1 (ru)	2017-10-31	Ингибиторы никотинамид фосфорибозилтрансферазы, композиции, продукты и их применение
US6121271A (en)	2000-09-19	Naphtho[2,3-B]heteroar-4-yl derivatives
US6004959A (en)	1999-12-21	Alkyloxyamino substituted fluorenones and their use as protein kinase-C inhibitors
NO172643B (no)	1993-05-10	Analogifremgangsmaate ved fremstilling av terapeutisk aktive benzopyranolderivater
US20060111368A1 (en)	2006-05-25	Phosphodiesterase inhibitor
PT101072A (pt)	1994-02-28	Derivados de piridinol,seu uso e processo de preparacao e composicoes farmaceuticas
US20060167055A1 (en)	2006-07-27	Non-nucleoside reverse transcriptase inhibitors
US4207335A (en)	1980-06-10	Indan-1,3-diones
US4136192A (en)	1979-01-23	4-hydroxy-3-nitro (cyano) coumarins
KR100542841B1 (ko)	2006-03-23	디알킬아미노알콕시기 치환된 플루오레논 및 이들의 단백질키나제c억제제로서의 용도