BG107889A - Тетралонови производни като антитуморни средства - Google Patents

Тетралонови производни като антитуморни средства Download PDF

Info

Publication number: BG107889A
Authority: BG; Bulgaria
Prior art keywords: oxo; alkyl; formula; tetrahydro; compound
Prior art date: 2000-12-07

Application number

BG107889A

Other languages

Bulgarian (bg)

English (en)

Inventor

Guy Georges

Adelbert Grossmann

Tim Sattelkau

Wolfgang Schaefer

Ulrich Tibes

Original Assignee

F. Hoffmann- La Roche Ag

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.)

2000-12-07

Filing date

2003-06-06

Publication date

2004-06-30

2003-06-06 Application filed by F. Hoffmann- La Roche Ag filed Critical F. Hoffmann- La Roche Ag

2004-06-30 Publication of BG107889A publication Critical patent/BG107889A/bg

Links

239000002246 antineoplastic agent Substances 0.000 title description 2
XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical class C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 title 1
-1 trifluoromethyl- Chemical group 0.000 claims abstract description 88
150000001875 compounds Chemical class 0.000 claims abstract description 76
125000000217 alkyl group Chemical group 0.000 claims abstract description 36
238000000034 method Methods 0.000 claims abstract description 26
239000001257 hydrogen Substances 0.000 claims abstract description 18
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
238000002360 preparation method Methods 0.000 claims abstract description 16
125000002947 alkylene group Chemical group 0.000 claims abstract description 8
125000003282 alkyl amino group Chemical group 0.000 claims abstract description 7
125000005530 alkylenedioxy group Chemical group 0.000 claims abstract description 7
125000005843 halogen group Chemical group 0.000 claims abstract description 7
125000005236 alkanoylamino group Chemical group 0.000 claims abstract description 6
125000002102 aryl alkyloxo group Chemical group 0.000 claims abstract description 6
125000004104 aryloxy group Chemical group 0.000 claims abstract description 6
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
125000003118 aryl group Chemical group 0.000 claims abstract description 5
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 5
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 5
229920006395 saturated elastomer Polymers 0.000 claims abstract description 5
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 3
125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract 3
239000002253 acid Substances 0.000 claims description 39
150000003839 salts Chemical class 0.000 claims description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
230000002401 inhibitory effect Effects 0.000 claims description 11
125000006239 protecting group Chemical group 0.000 claims description 10
102000003964 Histone deacetylase Human genes 0.000 claims description 9
108090000353 Histone deacetylase Proteins 0.000 claims description 9
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 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 6
150000007513 acids Chemical class 0.000 claims description 5
230000006907 apoptotic process Effects 0.000 claims description 5
IAZBYBYUBPQUTB-UHFFFAOYSA-N 5-(1-oxo-3,4-dihydro-2h-naphthalen-2-yl)pentanoic acid Chemical compound C1=CC=C2C(=O)C(CCCCC(=O)O)CCC2=C1 IAZBYBYUBPQUTB-UHFFFAOYSA-N 0.000 claims description 4
239000003795 chemical substances by application Substances 0.000 claims description 4
239000003112 inhibitor Substances 0.000 claims description 4
UCBZUTQDUKGSLA-UHFFFAOYSA-N 5-(6-methoxy-1-oxo-3,4-dihydro-2h-naphthalen-2-yl)pentanoic acid Chemical compound O=C1C(CCCCC(O)=O)CCC2=CC(OC)=CC=C21 UCBZUTQDUKGSLA-UHFFFAOYSA-N 0.000 claims description 3
MKDLFGQNUIBMNZ-UHFFFAOYSA-N 6-(6-chloro-1-oxo-3,4-dihydro-2h-naphthalen-2-yl)hexanoic acid Chemical compound ClC1=CC=C2C(=O)C(CCCCCC(=O)O)CCC2=C1 MKDLFGQNUIBMNZ-UHFFFAOYSA-N 0.000 claims description 3
239000004480 active ingredient Substances 0.000 claims description 3
IZDKPYIYPJAFJZ-UHFFFAOYSA-N ethyl 2-[6-(hydroxyamino)-6-oxohexyl]-5-methoxy-1-oxo-3,4-dihydronaphthalene-2-carboxylate Chemical compound C1=CC=C2C(=O)C(C(=O)OCC)(CCCCCC(=O)NO)CCC2=C1OC IZDKPYIYPJAFJZ-UHFFFAOYSA-N 0.000 claims description 3
150000002431 hydrogen Chemical class 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
KZCDUXUPGMFKCR-UHFFFAOYSA-N 5-(5-methoxy-1-oxo-3,4-dihydro-2h-naphthalen-2-yl)hexanoic acid Chemical compound O=C1C(C(C)CCCC(O)=O)CCC2=C1C=CC=C2OC KZCDUXUPGMFKCR-UHFFFAOYSA-N 0.000 claims description 2
CCALHTAFIMKDNW-UHFFFAOYSA-N 6-(2-methyl-1-oxo-3,4-dihydronaphthalen-2-yl)hexanoic acid Chemical compound C1=CC=C2C(=O)C(C)(CCCCCC(O)=O)CCC2=C1 CCALHTAFIMKDNW-UHFFFAOYSA-N 0.000 claims description 2
230000004663 cell proliferation Effects 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
YBCLTVGPNJHRDS-UHFFFAOYSA-N 5-(2-methyl-1-oxo-3,4-dihydronaphthalen-2-yl)pentanoic acid Chemical compound C1=CC=C2C(=O)C(C)(CCCCC(O)=O)CCC2=C1 YBCLTVGPNJHRDS-UHFFFAOYSA-N 0.000 claims 1
IXROREAZFLSHEC-UHFFFAOYSA-N 6-(2-methyl-1-oxo-3,4-dihydronaphthalen-2-yl)hex-5-enoic acid Chemical compound C1=CC=C2C(=O)C(C)(C=CCCCC(O)=O)CCC2=C1 IXROREAZFLSHEC-UHFFFAOYSA-N 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
OYWNDBDTJYUDHD-UHFFFAOYSA-N ethyl 2-[8-(hydroxyamino)-8-oxooctyl]-5,7-dimethyl-1-oxo-3,4-dihydronaphthalene-2-carboxylate Chemical compound C1=C(C)C=C2C(=O)C(C(=O)OCC)(CCCCCCCC(=O)NO)CCC2=C1C OYWNDBDTJYUDHD-UHFFFAOYSA-N 0.000 claims 1
230000001939 inductive effect Effects 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 8
239000003276 histone deacetylase inhibitor Substances 0.000 abstract description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
229940121372 histone deacetylase inhibitor Drugs 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
238000006243 chemical reaction Methods 0.000 description 43
239000000243 solution Substances 0.000 description 35
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
239000000203 mixture Substances 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
239000012442 inert solvent Substances 0.000 description 13
238000011282 treatment Methods 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
239000002585 base Substances 0.000 description 10
238000004440 column chromatography Methods 0.000 description 10
238000001704 evaporation Methods 0.000 description 10
239000002904 solvent Substances 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
230000008020 evaporation Effects 0.000 description 9
241001465754 Metazoa Species 0.000 description 8
206010028980 Neoplasm Diseases 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
238000003756 stirring Methods 0.000 description 8
239000000969 carrier Substances 0.000 description 7
150000002148 esters Chemical group 0.000 description 7
239000003701 inert diluent Substances 0.000 description 7
239000004615 ingredient Substances 0.000 description 7
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
201000011510 cancer Diseases 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
239000000047 product Substances 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
150000001540 azides Chemical class 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
238000002347 injection Methods 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
230000035755 proliferation Effects 0.000 description 5
239000011734 sodium Substances 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
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 4
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 4
KLDLRDSRCMJKGM-UHFFFAOYSA-N 3-[chloro-(2-oxo-1,3-oxazolidin-3-yl)phosphoryl]-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1P(=O)(Cl)N1CCOC1=O KLDLRDSRCMJKGM-UHFFFAOYSA-N 0.000 description 4
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 4
241000282414 Homo sapiens Species 0.000 description 4
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
230000000259 anti-tumor effect Effects 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
239000002775 capsule Substances 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
239000012043 crude product Substances 0.000 description 4
125000004122 cyclic group Chemical group 0.000 description 4
125000004494 ethyl ester group Chemical group 0.000 description 4
239000007903 gelatin capsule Substances 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
229920005862 polyol Polymers 0.000 description 4
150000003077 polyols Chemical class 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
238000000926 separation method Methods 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
GANIBVZSZGNMNB-UHFFFAOYSA-N 2-methyl-1-tetralone Chemical compound C1=CC=C2C(=O)C(C)CCC2=C1 GANIBVZSZGNMNB-UHFFFAOYSA-N 0.000 description 3
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
239000011248 coating agent Substances 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
DXBULVYHTICWKT-UHFFFAOYSA-N ethyl 6-bromohexanoate Chemical compound CCOC(=O)CCCCCBr DXBULVYHTICWKT-UHFFFAOYSA-N 0.000 description 3
239000008187 granular material Substances 0.000 description 3
238000005984 hydrogenation reaction Methods 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
230000014759 maintenance of location Effects 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 3
239000002245 particle Substances 0.000 description 3
239000000825 pharmaceutical preparation Substances 0.000 description 3
239000012071 phase Substances 0.000 description 3
229910052697 platinum Inorganic materials 0.000 description 3
238000010992 reflux Methods 0.000 description 3
238000011894 semi-preparative HPLC Methods 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
239000000829 suppository Substances 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
238000012360 testing method Methods 0.000 description 3
238000013518 transcription Methods 0.000 description 3
230000035897 transcription Effects 0.000 description 3
SCZNXLWKYFICFV-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound C1CCCNN2CCCC=C21 SCZNXLWKYFICFV-UHFFFAOYSA-N 0.000 description 2
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 2
UVDSHNDBNRROHT-UHFFFAOYSA-N 5-(6-methoxy-1-oxo-3,4-dihydro-2h-naphthalen-2-yl)-n-phenylmethoxypentanamide Chemical compound C1CC2=CC(OC)=CC=C2C(=O)C1CCCCC(=O)NOCC1=CC=CC=C1 UVDSHNDBNRROHT-UHFFFAOYSA-N 0.000 description 2
MVSZWCKOBYOXBB-UHFFFAOYSA-N 6-(5-methoxy-1-oxo-3,4-dihydro-2h-naphthalen-2-yl)hexanoic acid Chemical compound O=C1C(CCCCCC(O)=O)CCC2=C1C=CC=C2OC MVSZWCKOBYOXBB-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
108020004414 DNA Proteins 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
102000006947 Histones Human genes 0.000 description 2
108010033040 Histones Proteins 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
108010047956 Nucleosomes Proteins 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
230000021736 acetylation Effects 0.000 description 2
238000006640 acetylation reaction Methods 0.000 description 2
230000003213 activating effect Effects 0.000 description 2
230000004913 activation Effects 0.000 description 2
239000013543 active substance Substances 0.000 description 2
150000001263 acyl chlorides Chemical class 0.000 description 2
150000001264 acyl cyanides Chemical class 0.000 description 2
150000001266 acyl halides Chemical class 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 description 2
HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 2
239000000010 aprotic solvent Substances 0.000 description 2
239000003849 aromatic solvent Substances 0.000 description 2
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C233/60—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- 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
- C07D295/10—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 doubly bound oxygen or sulphur atoms
- C07D295/112—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 doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- C07D295/116—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 doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings with the doubly bound oxygen or sulfur atoms directly attached to a carbocyclic ring
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
- C07D213/50—Ketonic radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Hematology (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

BG107889A 2000-12-07 2003-06-06 Тетралонови производни като антитуморни средства BG107889A (bg)

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EP00126820		2000-12-07
PCT/EP2001/014311 WO2002046144A1 (en)	2000-12-07	2001-12-06	Tetralone derivatives as antitumor agents

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US (1)	US6531472B2 (cs)
EP (1)	EP1349830A1 (cs)
JP (1)	JP4091431B2 (cs)
KR (1)	KR20030077551A (cs)
CN (1)	CN100340545C (cs)
AR (1)	AR035659A1 (cs)
AU (2)	AU1607402A (cs)
BG (1)	BG107889A (cs)
BR (1)	BR0115988A (cs)
CA (1)	CA2430355A1 (cs)
CZ (1)	CZ20031833A3 (cs)
EC (1)	ECSP034642A (cs)
HR (1)	HRP20030451A2 (cs)
HU (1)	HUP0400579A2 (cs)
IL (1)	IL156133A0 (cs)
MA (1)	MA26972A1 (cs)
MX (1)	MXPA03004947A (cs)
NO (1)	NO20032531L (cs)
NZ (1)	NZ526051A (cs)
PL (1)	PL365324A1 (cs)
RU (1)	RU2288220C2 (cs)
SK (1)	SK8512003A3 (cs)
WO (1)	WO2002046144A1 (cs)
YU (1)	YU45803A (cs)
ZA (1)	ZA200304262B (cs)

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2001
- 2001-11-27 AR ARP010105504A patent/AR035659A1/es not_active Application Discontinuation
- 2001-12-04 US US10/006,173 patent/US6531472B2/en not_active Expired - Fee Related
- 2001-12-06 RU RU2003119658/04A patent/RU2288220C2/ru active
- 2001-12-06 BR BR0115988-7A patent/BR0115988A/pt not_active IP Right Cessation
- 2001-12-06 CA CA002430355A patent/CA2430355A1/en not_active Abandoned
- 2001-12-06 AU AU1607402A patent/AU1607402A/xx active Pending
- 2001-12-06 YU YU45803A patent/YU45803A/sh unknown
- 2001-12-06 HU HU0400579A patent/HUP0400579A2/hu unknown
- 2001-12-06 SK SK851-2003A patent/SK8512003A3/sk unknown
- 2001-12-06 IL IL15613301A patent/IL156133A0/xx unknown
- 2001-12-06 CN CNB018197345A patent/CN100340545C/zh not_active Expired - Fee Related
- 2001-12-06 MX MXPA03004947A patent/MXPA03004947A/es active IP Right Grant
- 2001-12-06 CZ CZ20031833A patent/CZ20031833A3/cs unknown
- 2001-12-06 EP EP01999552A patent/EP1349830A1/en not_active Withdrawn
- 2001-12-06 JP JP2002547883A patent/JP4091431B2/ja not_active Expired - Fee Related
- 2001-12-06 WO PCT/EP2001/014311 patent/WO2002046144A1/en not_active Ceased
- 2001-12-06 NZ NZ526051A patent/NZ526051A/xx unknown
- 2001-12-06 PL PL01365324A patent/PL365324A1/xx not_active Application Discontinuation
- 2001-12-06 KR KR10-2003-7007640A patent/KR20030077551A/ko not_active Ceased
- 2001-12-06 HR HR20030451A patent/HRP20030451A2/hr not_active Application Discontinuation
- 2001-12-06 AU AU2002216074A patent/AU2002216074C1/en not_active Ceased
2003
- 2003-05-30 ZA ZA200304262A patent/ZA200304262B/en unknown
- 2003-06-04 MA MA27193A patent/MA26972A1/fr unknown
- 2003-06-04 NO NO20032531A patent/NO20032531L/no not_active Application Discontinuation
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Also Published As

Publication number	Publication date
KR20030077551A (ko)	2003-10-01
NZ526051A (en)	2004-12-24
EP1349830A1 (en)	2003-10-08
JP4091431B2 (ja)	2008-05-28
CZ20031833A3 (cs)	2004-02-18
CN1478072A (zh)	2004-02-25
AU2002216074B2 (en)	2006-01-05
RU2288220C2 (ru)	2006-11-27
WO2002046144A1 (en)	2002-06-13
HRP20030451A2 (en)	2005-04-30
AU1607402A (en)	2002-06-18
ECSP034642A (es)	2003-07-25
SK8512003A3 (en)	2004-04-06
US20020065282A1 (en)	2002-05-30
MA26972A1 (fr)	2004-12-20
US6531472B2 (en)	2003-03-11
PL365324A1 (en)	2004-12-27
YU45803A (sh)	2006-05-25
CA2430355A1 (en)	2002-06-13
NO20032531D0 (no)	2003-06-04
HUP0400579A2 (hu)	2004-06-28
JP2004515488A (ja)	2004-05-27
IL156133A0 (en)	2003-12-23
BR0115988A (pt)	2004-01-13
MXPA03004947A (es)	2003-09-10
AU2002216074C1 (en)	2006-12-07
AR035659A1 (es)	2004-06-23
CN100340545C (zh)	2007-10-03
ZA200304262B (en)	2004-08-30
HK1060875A1 (en)	2004-08-27
NO20032531L (no)	2003-06-04

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