JP2003535868A - 抗腫瘍化合物 - Google Patents
抗腫瘍化合物Info
- Publication number
- JP2003535868A JP2003535868A JP2002501905A JP2002501905A JP2003535868A JP 2003535868 A JP2003535868 A JP 2003535868A JP 2002501905 A JP2002501905 A JP 2002501905A JP 2002501905 A JP2002501905 A JP 2002501905A JP 2003535868 A JP2003535868 A JP 2003535868A
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- unsubstituted
- mmol
- salt
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims description 51
- 230000000259 anti-tumor effect Effects 0.000 title description 4
- 238000000034 method Methods 0.000 claims description 111
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 125000000217 alkyl group Chemical group 0.000 claims description 41
- 150000003839 salts Chemical class 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 229910052799 carbon Inorganic materials 0.000 claims description 27
- 125000003342 alkenyl group Chemical group 0.000 claims description 25
- -1 amino, dibenzylamino Chemical group 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 24
- 125000000304 alkynyl group Chemical group 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Chemical group 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 5
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 298
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 211
- 239000000126 substance Substances 0.000 description 163
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 112
- 235000019439 ethyl acetate Nutrition 0.000 description 104
- 239000007787 solid Substances 0.000 description 95
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 51
- 150000001414 amino alcohols Chemical class 0.000 description 48
- 125000004432 carbon atom Chemical group C* 0.000 description 46
- 239000000243 solution Substances 0.000 description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 239000012230 colorless oil Substances 0.000 description 42
- 150000001299 aldehydes Chemical class 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- 239000000460 chlorine Substances 0.000 description 29
- 238000003756 stirring Methods 0.000 description 29
- 239000000377 silicon dioxide Substances 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 24
- 238000004440 column chromatography Methods 0.000 description 24
- 239000012043 crude product Substances 0.000 description 24
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 23
- 150000003462 sulfoxides Chemical class 0.000 description 22
- 239000002904 solvent Substances 0.000 description 18
- 150000002576 ketones Chemical class 0.000 description 14
- 229910052760 oxygen Inorganic materials 0.000 description 13
- 238000000746 purification Methods 0.000 description 12
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- JKOTZBXSNOGCIF-UHFFFAOYSA-N 1-bromopentadecane Chemical compound CCCCCCCCCCCCCCCBr JKOTZBXSNOGCIF-UHFFFAOYSA-N 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000012267 brine Substances 0.000 description 7
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000001540 azides Chemical class 0.000 description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 150000002430 hydrocarbons Chemical group 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- KKUKTXOBAWVSHC-UHFFFAOYSA-N Dimethylphosphate Chemical compound COP(O)(=O)OC KKUKTXOBAWVSHC-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- 229910010082 LiAlH Inorganic materials 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- 239000004809 Teflon Substances 0.000 description 3
- 229920006362 Teflon® Polymers 0.000 description 3
- 125000002015 acyclic group Chemical group 0.000 description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 125000004414 alkyl thio group Chemical group 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 2
- JCBPETKZIGVZRE-BYPYZUCNSA-N (2s)-2-aminobutan-1-ol Chemical compound CC[C@H](N)CO JCBPETKZIGVZRE-BYPYZUCNSA-N 0.000 description 2
- SZXBQTSZISFIAO-ZETCQYMHSA-N (2s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C SZXBQTSZISFIAO-ZETCQYMHSA-N 0.000 description 2
- LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 description 2
- HHSDZLLPIXMEIU-UHFFFAOYSA-N 1-bromoheptadecane Chemical compound CCCCCCCCCCCCCCCCCBr HHSDZLLPIXMEIU-UHFFFAOYSA-N 0.000 description 2
- HNTGIJLWHDPAFN-UHFFFAOYSA-N 1-bromohexadecane Chemical compound CCCCCCCCCCCCCCCCBr HNTGIJLWHDPAFN-UHFFFAOYSA-N 0.000 description 2
- KOFZTCSTGIWCQG-UHFFFAOYSA-N 1-bromotetradecane Chemical compound CCCCCCCCCCCCCCBr KOFZTCSTGIWCQG-UHFFFAOYSA-N 0.000 description 2
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 101100214874 Autographa californica nuclear polyhedrosis virus AC81 gene Proteins 0.000 description 2
- VDRZDTXJMRRVMF-UONOGXRCSA-N D-erythro-sphingosine Natural products CCCCCCCCCC=C[C@@H](O)[C@@H](N)CO VDRZDTXJMRRVMF-UONOGXRCSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
- 238000000119 electrospray ionisation mass spectrum Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 102220240796 rs553605556 Human genes 0.000 description 2
- 239000001384 succinic acid Substances 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- 150000003512 tertiary amines Chemical group 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 229960004295 valine Drugs 0.000 description 2
- IEEFFKXJADVWJO-OAHLLOKOSA-N (2r)-2-(dibenzylamino)propan-1-ol Chemical compound C=1C=CC=CC=1CN([C@@H](CO)C)CC1=CC=CC=C1 IEEFFKXJADVWJO-OAHLLOKOSA-N 0.000 description 1
- GFYXFRCVQSKSDO-OAHLLOKOSA-N (2r)-2-(dibenzylamino)propanal Chemical compound C=1C=CC=CC=1CN([C@@H](C=O)C)CC1=CC=CC=C1 GFYXFRCVQSKSDO-OAHLLOKOSA-N 0.000 description 1
- CJIILUGXXXKRTA-UNTBIKODSA-N (2r)-2-aminooctadecan-3-one;hydrochloride Chemical compound Cl.CCCCCCCCCCCCCCCC(=O)[C@@H](C)N CJIILUGXXXKRTA-UNTBIKODSA-N 0.000 description 1
- AUGRPIHBMZBMKB-PPTMTGTBSA-N (2r,3s)-2-(dibenzylamino)octadecan-3-ol Chemical compound C=1C=CC=CC=1CN([C@H](C)[C@@H](O)CCCCCCCCCCCCCCC)CC1=CC=CC=C1 AUGRPIHBMZBMKB-PPTMTGTBSA-N 0.000 description 1
- YRYJJIXWWQLGGV-MSOLQXFVSA-N (2r,3s)-2-aminooctadecan-3-ol Chemical compound CCCCCCCCCCCCCCC[C@H](O)[C@@H](C)N YRYJJIXWWQLGGV-MSOLQXFVSA-N 0.000 description 1
- LHAUQAAPXGACHN-XIFFEERXSA-N (2s)-2,5-bis(dibenzylamino)pentan-1-ol Chemical compound C([C@@H](CO)N(CC=1C=CC=CC=1)CC=1C=CC=CC=1)CCN(CC=1C=CC=CC=1)CC1=CC=CC=C1 LHAUQAAPXGACHN-XIFFEERXSA-N 0.000 description 1
- WUAUOTVCWFISNJ-XIFFEERXSA-N (2s)-2,5-bis(dibenzylamino)pentanal Chemical compound C([C@@H](C=O)N(CC=1C=CC=CC=1)CC=1C=CC=CC=1)CCN(CC=1C=CC=CC=1)CC1=CC=CC=C1 WUAUOTVCWFISNJ-XIFFEERXSA-N 0.000 description 1
- NEYQXBDXTXAJPH-LJAQVGFWSA-N (2s)-2-(dibenzylamino)-3-(4-phenylmethoxyphenyl)propan-1-ol Chemical compound C([C@@H](CO)N(CC=1C=CC=CC=1)CC=1C=CC=CC=1)C(C=C1)=CC=C1OCC1=CC=CC=C1 NEYQXBDXTXAJPH-LJAQVGFWSA-N 0.000 description 1
- UBNRYFHVXKUNLV-LJAQVGFWSA-N (2s)-2-(dibenzylamino)-3-(4-phenylmethoxyphenyl)propanal Chemical compound C([C@@H](C=O)N(CC=1C=CC=CC=1)CC=1C=CC=CC=1)C(C=C1)=CC=C1OCC1=CC=CC=C1 UBNRYFHVXKUNLV-LJAQVGFWSA-N 0.000 description 1
- ZWLAXLXECFRUPM-LJQANCHMSA-N (2s)-2-(dibenzylamino)-3-methylbutan-1-ol Chemical compound C=1C=CC=CC=1CN([C@H](CO)C(C)C)CC1=CC=CC=C1 ZWLAXLXECFRUPM-LJQANCHMSA-N 0.000 description 1
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- RWDGCGHIPSWDTF-SFHVURJKSA-N (2s)-2-(dibenzylamino)butan-1-ol Chemical compound C=1C=CC=CC=1CN([C@H](CO)CC)CC1=CC=CC=C1 RWDGCGHIPSWDTF-SFHVURJKSA-N 0.000 description 1
- QJOKRFSPLJVARG-SFHVURJKSA-N (2s)-2-(dibenzylamino)butanal Chemical compound C=1C=CC=CC=1CN([C@H](C=O)CC)CC1=CC=CC=C1 QJOKRFSPLJVARG-SFHVURJKSA-N 0.000 description 1
- UUOVWTITZBZUOU-IBGZPJMESA-N (2s)-2-(dibenzylamino)pentan-1-ol Chemical compound C=1C=CC=CC=1CN([C@H](CO)CCC)CC1=CC=CC=C1 UUOVWTITZBZUOU-IBGZPJMESA-N 0.000 description 1
- XQGBOVZZVRZAPI-IBGZPJMESA-N (2s)-2-(dibenzylamino)pentanal Chemical compound C=1C=CC=CC=1CN([C@H](C=O)CCC)CC1=CC=CC=C1 XQGBOVZZVRZAPI-IBGZPJMESA-N 0.000 description 1
- GFYXFRCVQSKSDO-HNNXBMFYSA-N (2s)-2-(dibenzylamino)propanal Chemical compound C=1C=CC=CC=1CN([C@H](C=O)C)CC1=CC=CC=C1 GFYXFRCVQSKSDO-HNNXBMFYSA-N 0.000 description 1
- VJWLDAUJROTQMV-NTISSMGPSA-N (2s)-2-aminoheptadecan-3-one;hydrochloride Chemical compound Cl.CCCCCCCCCCCCCCC(=O)[C@H](C)N VJWLDAUJROTQMV-NTISSMGPSA-N 0.000 description 1
- BVYAQELNVWDOGL-FERBBOLQSA-N (2s)-2-aminononadecan-3-one;hydrochloride Chemical compound Cl.CCCCCCCCCCCCCCCCC(=O)[C@H](C)N BVYAQELNVWDOGL-FERBBOLQSA-N 0.000 description 1
- CJIILUGXXXKRTA-LMOVPXPDSA-N (2s)-2-aminooctadecan-3-one;hydrochloride Chemical compound Cl.CCCCCCCCCCCCCCCC(=O)[C@H](C)N CJIILUGXXXKRTA-LMOVPXPDSA-N 0.000 description 1
- KVTLSBYHFYBBFH-YWPUXERESA-N (2s,3r)-2-(dibenzylamino)-1-(4-phenylmethoxyphenyl)octadecan-3-ol Chemical compound C([C@@H]([C@H](O)CCCCCCCCCCCCCCC)N(CC=1C=CC=CC=1)CC=1C=CC=CC=1)C(C=C1)=CC=C1OCC1=CC=CC=C1 KVTLSBYHFYBBFH-YWPUXERESA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
- C07D263/24—Oxygen atoms attached in position 2 with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/02—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C211/15—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
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- C07C215/06—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic
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- C07C215/48—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups
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- 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
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- C07C219/06—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having the hydroxy groups esterified by carboxylic acids having the esterifying carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms of an acyclic saturated carbon skeleton
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- C07C225/04—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being saturated
- C07C225/06—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being saturated and acyclic
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- C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms 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
- C07C233/17—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms 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 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/18—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms 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 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
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- C07C233/22—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms 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 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
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- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
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- C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
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- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C251/36—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atoms of the oxyimino groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C251/38—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atoms of the oxyimino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of a saturated carbon skeleton
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- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
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- C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
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- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
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- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/04—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms
- C07C275/06—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an acyclic and saturated carbon skeleton
- C07C275/10—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an acyclic and saturated carbon skeleton being further substituted by singly-bound oxygen atoms
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- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
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- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/04—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
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- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
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- C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
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- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
- C07D263/22—Oxygen atoms attached in position 2 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to other ring carbon atoms
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Applications Claiming Priority (7)
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| GB0013783A GB0013783D0 (en) | 2000-06-06 | 2000-06-06 | New antitumoral derivatives of spisulosine-285 |
| GB0013783.6 | 2000-06-06 | ||
| GB0102472.8 | 2001-01-31 | ||
| GB0102472A GB0102472D0 (en) | 2001-01-31 | 2001-01-31 | New antitumoral derivatives of spisulosine-285 |
| GB0104732.3 | 2001-02-26 | ||
| GB0104732A GB0104732D0 (en) | 2001-02-26 | 2001-02-26 | New antitumoral derivatives of spisulosine-285 |
| PCT/GB2001/002487 WO2001094357A1 (en) | 2000-06-06 | 2001-06-06 | Antitumoral compounds |
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| JP2003535868A true JP2003535868A (ja) | 2003-12-02 |
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| JP2017128518A (ja) * | 2016-01-19 | 2017-07-27 | 塩野義製薬株式会社 | Sms2阻害活性を有するセラミド誘導体 |
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| WO2003005965A2 (en) * | 2001-07-11 | 2003-01-23 | Musc Foundation For Research Development | Modulators of ceramidase and methods of use based thereon |
| FR2847473B1 (fr) * | 2002-11-25 | 2007-06-29 | Expanscience Lab | Composition comprenant au moins une oxazolidinone, son utilisation cosmetique et comme medicament |
| US7960589B2 (en) * | 2006-09-06 | 2011-06-14 | Emory University | Synthesis of sphingosines and their derivatives |
| US8431733B2 (en) * | 2008-03-12 | 2013-04-30 | Virobay, Inc. | Process for the preparation of (3S)-3-amino-N-cyclopropyl-2-hydroxyalkanamide derivatives |
| WO2014118556A2 (en) * | 2013-01-31 | 2014-08-07 | Research Foundation Of The City University Of New York | Selective inhibitors and allosteric activators of sphingosine kinase |
| JOP20190254A1 (ar) | 2017-04-27 | 2019-10-27 | Pharma Mar Sa | مركبات مضادة للأورام |
Citations (1)
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| WO1999052521A1 (en) * | 1998-04-10 | 1999-10-21 | The Board Of Trustees Of The University Of Illinois | Spisulosine compounds having antitumour activity |
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| GB546383A (en) * | 1940-10-08 | 1942-07-10 | Frank Lodge | New wool dyestuffs |
| US2399118A (en) | 1942-02-13 | 1946-04-23 | Mallinckrodt Chemical Works | 2-oxazolidone compounds and method for preparing the same |
| US2363082A (en) * | 1943-01-20 | 1944-11-21 | Novocol Chemical Mfg Co Inc | Anesthetic compounds, intermediates, and processes therefor |
| US2424311A (en) * | 1943-11-10 | 1947-07-22 | Merck & Co Inc | Process for making esters of 7,8-diamino nonoic acid |
| DE828547C (de) * | 1949-08-21 | 1952-01-17 | Cassella Farbwerke Mainkur Ag | Verfahren zur Herstellung von Komplexsalzbildnern |
| GB1057651A (en) * | 1963-01-16 | 1967-02-08 | Merck & Co Inc | Chlorinated amino acids and their preparation |
| GB1433920A (en) | 1973-10-01 | 1976-04-28 | Ici Ltd | Alkanolamine derivatives |
| US6800661B1 (en) * | 1997-04-15 | 2004-10-05 | Board Of Trustees Of The University Of Illinois | Spisulosine compounds |
| US6756504B2 (en) * | 2000-04-19 | 2004-06-29 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Sphingolipids |
| EP1363643A2 (en) * | 2000-12-22 | 2003-11-26 | Medlyte, Inc. | Compositions and methods for the treatment and prevention of cardiovascular diseases and disorders, and for identifying agents therapeutic therefor |
| JP3692492B2 (ja) * | 2001-05-01 | 2005-09-07 | 独立行政法人科学技術振興機構 | 新規なスフィンゴ脂質合成阻害剤 |
| WO2003045928A1 (en) * | 2001-11-26 | 2003-06-05 | Genzyme Corporation | Diastereoselective synthesis of udp-glucose : n-acylsphingosine glucosyltransferase inhibitors |
| BR0205172A (pt) * | 2001-12-20 | 2004-06-29 | Cosmoferm Bv | Processo para a sìntese de esfingosina |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO1999052521A1 (en) * | 1998-04-10 | 1999-10-21 | The Board Of Trustees Of The University Of Illinois | Spisulosine compounds having antitumour activity |
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|---|---|---|---|---|
| JP2017128518A (ja) * | 2016-01-19 | 2017-07-27 | 塩野義製薬株式会社 | Sms2阻害活性を有するセラミド誘導体 |
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| EP1287006A1 (en) | 2003-03-05 |
| DE60131076D1 (de) | 2007-12-06 |
| ATE376552T1 (de) | 2007-11-15 |
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| CA2410409A1 (en) | 2001-12-13 |
| AU2001262518B2 (en) | 2006-10-26 |
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| ES2293996T3 (es) | 2008-04-01 |
| US7138547B2 (en) | 2006-11-21 |
| US20040048834A1 (en) | 2004-03-11 |
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