IL96946A - תולדות חומצה בורונית, שיטות וערכות לאבחנה המכילות אותן - Google Patents
תולדות חומצה בורונית, שיטות וערכות לאבחנה המכילות אותןInfo
- Publication number
- IL96946A IL96946A IL9694691A IL9694691A IL96946A IL 96946 A IL96946 A IL 96946A IL 9694691 A IL9694691 A IL 9694691A IL 9694691 A IL9694691 A IL 9694691A IL 96946 A IL96946 A IL 96946A
- Authority
- IL
- Israel
- Prior art keywords
- boronic acid
- accordance
- name
- dioxime
- compound according
- Prior art date
Links
- 229910052702 rhenium Inorganic materials 0.000 title claims abstract description 23
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 229940056501 technetium 99m Drugs 0.000 title claims abstract description 18
- 150000001642 boronic acid derivatives Chemical class 0.000 title claims abstract description 13
- 238000009007 Diagnostic Kit Methods 0.000 title description 2
- 238000002405 diagnostic procedure Methods 0.000 title description 2
- GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims description 65
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 40
- 206010021143 Hypoxia Diseases 0.000 claims description 36
- JGUQDUKBUKFFRO-CIIODKQPSA-N dimethylglyoxime Chemical group O/N=C(/C)\C(\C)=N\O JGUQDUKBUKFFRO-CIIODKQPSA-N 0.000 claims description 34
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 32
- 239000000203 mixture Substances 0.000 claims description 28
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 24
- 239000000460 chlorine Substances 0.000 claims description 24
- 229910052801 chlorine Inorganic materials 0.000 claims description 24
- 230000001404 mediated effect Effects 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 230000007954 hypoxia Effects 0.000 claims description 23
- 239000000758 substrate Substances 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- -1 barbiturates Chemical class 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 229910052796 boron Inorganic materials 0.000 claims description 15
- 102000005962 receptors Human genes 0.000 claims description 15
- 108020003175 receptors Proteins 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 claims description 14
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 claims description 14
- 210000004556 brain Anatomy 0.000 claims description 14
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 13
- 150000001412 amines Chemical class 0.000 claims description 13
- 150000001450 anions Chemical group 0.000 claims description 13
- 238000002059 diagnostic imaging Methods 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 230000001146 hypoxic effect Effects 0.000 claims description 13
- 150000003431 steroids Chemical class 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 12
- 125000006850 spacer group Chemical group 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical group 0.000 claims description 10
- 210000004072 lung Anatomy 0.000 claims description 10
- 102000015694 estrogen receptors Human genes 0.000 claims description 9
- 108010038795 estrogen receptors Proteins 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 229960005309 estradiol Drugs 0.000 claims description 8
- 229930182833 estradiol Natural products 0.000 claims description 8
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical group OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 150000003973 alkyl amines Chemical class 0.000 claims description 7
- HLAVRMXKLBAPSL-UHFFFAOYSA-N benzylboron Chemical compound [B]CC1=CC=CC=C1 HLAVRMXKLBAPSL-UHFFFAOYSA-N 0.000 claims description 7
- 239000003638 chemical reducing agent Substances 0.000 claims description 7
- 239000000194 fatty acid Substances 0.000 claims description 7
- 150000004820 halides Chemical group 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 7
- 230000002503 metabolic effect Effects 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 238000001959 radiotherapy Methods 0.000 claims description 7
- UDVCEIBYNGPBFN-WAJSLEGFSA-N [B].[C@@H]12CCC(O)[C@@]1(C)CC[C@@H]1C3=C(CC[C@@H]21)C=C(O)C=C3 Chemical compound [B].[C@@H]12CCC(O)[C@@]1(C)CC[C@@H]1C3=C(CC[C@@H]21)C=C(O)C=C3 UDVCEIBYNGPBFN-WAJSLEGFSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 6
- 229940011871 estrogen Drugs 0.000 claims description 6
- 239000000262 estrogen Substances 0.000 claims description 6
- 229930195729 fatty acid Natural products 0.000 claims description 6
- 150000004665 fatty acids Chemical class 0.000 claims description 6
- 235000021588 free fatty acids Nutrition 0.000 claims description 6
- 210000002216 heart Anatomy 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 235000000346 sugar Nutrition 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 201000008275 breast carcinoma Diseases 0.000 claims description 5
- 150000002159 estradiols Chemical class 0.000 claims description 5
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical group C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 claims description 4
- XETLOFNELZCXMX-UHFFFAOYSA-N 2-(diethylamino)ethyl 2-(4-hexoxyphenyl)-2-hydroxy-2-phenylacetate;hydrochloride Chemical compound Cl.C1=CC(OCCCCCC)=CC=C1C(O)(C(=O)OCCN(CC)CC)C1=CC=CC=C1 XETLOFNELZCXMX-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 150000008163 sugars Chemical class 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 150000004959 2-nitroimidazoles Chemical class 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical group [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
- 102000015554 Dopamine receptor Human genes 0.000 claims description 3
- 108050004812 Dopamine receptor Proteins 0.000 claims description 3
- 102000010909 Monoamine Oxidase Human genes 0.000 claims description 3
- 108010062431 Monoamine oxidase Proteins 0.000 claims description 3
- 108010085012 Steroid Receptors Proteins 0.000 claims description 3
- 239000002220 antihypertensive agent Substances 0.000 claims description 3
- 229940030600 antihypertensive agent Drugs 0.000 claims description 3
- 229940125717 barbiturate Drugs 0.000 claims description 3
- 150000001638 boron Chemical class 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 102000005969 steroid hormone receptors Human genes 0.000 claims description 3
- 229940124530 sulfonamide Drugs 0.000 claims description 3
- 150000003456 sulfonamides Chemical class 0.000 claims description 3
- ALNUOSXDMYFQNQ-UHFFFAOYSA-N 2-nitro-1,3-thiazole Chemical class [O-][N+](=O)C1=NC=CS1 ALNUOSXDMYFQNQ-UHFFFAOYSA-N 0.000 claims description 2
- 150000004960 4-nitroimidazoles Chemical class 0.000 claims description 2
- 150000004958 5-nitroimidazoles Chemical class 0.000 claims description 2
- MMJILOHTNKKELU-UHFFFAOYSA-N N-(3-hydroperoxyiminobutan-2-ylidene)hydroxylamine Chemical compound CC(=NO)C(C)=NOO MMJILOHTNKKELU-UHFFFAOYSA-N 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- CUNNCKOPAWXYDX-KQQUZDAGSA-N (NE)-N-[(2E)-2-hydroxyiminocyclohexylidene]hydroxylamine Chemical group O\N=C1/CCCC/C/1=N\O CUNNCKOPAWXYDX-KQQUZDAGSA-N 0.000 claims 8
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 4
- ZTBIQJONGXVDJZ-UHFFFAOYSA-N N-(2-hydroxyiminocyclopentylidene)hydroxylamine Chemical group ON=C1CCCC1=NO ZTBIQJONGXVDJZ-UHFFFAOYSA-N 0.000 claims 2
- 150000001805 chlorine compounds Chemical group 0.000 claims 2
- FUBFWTUFPGFHOJ-UHFFFAOYSA-N 2-nitrofuran Chemical class [O-][N+](=O)C1=CC=CO1 FUBFWTUFPGFHOJ-UHFFFAOYSA-N 0.000 claims 1
- HGMITUYOCPPQLE-UHFFFAOYSA-N 3-quinuclidinyl benzilate Chemical group C1N(CC2)CCC2C1OC(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 HGMITUYOCPPQLE-UHFFFAOYSA-N 0.000 claims 1
- XBVRCZYRNIBBND-UHFFFAOYSA-N CC(C)NC(CC1=CC=C(C=C1)[B])C Chemical compound CC(C)NC(CC1=CC=C(C=C1)[B])C XBVRCZYRNIBBND-UHFFFAOYSA-N 0.000 claims 1
- 201000009030 Carcinoma Diseases 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 150000001721 carbon Chemical group 0.000 claims 1
- 238000011065 in-situ storage Methods 0.000 claims 1
- 238000002372 labelling Methods 0.000 claims 1
- 206010046766 uterine cancer Diseases 0.000 claims 1
- 208000012991 uterine carcinoma Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 3
- 230000002285 radioactive effect Effects 0.000 abstract description 2
- 229940124597 therapeutic agent Drugs 0.000 abstract description 2
- 229940039227 diagnostic agent Drugs 0.000 abstract 1
- 239000000032 diagnostic agent Substances 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 47
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
- 239000000243 solution Substances 0.000 description 44
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 39
- 238000002360 preparation method Methods 0.000 description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 35
- 238000004128 high performance liquid chromatography Methods 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- 239000007787 solid Substances 0.000 description 29
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 239000000047 product Substances 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 235000019441 ethanol Nutrition 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
- 230000027455 binding Effects 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- 238000003384 imaging method Methods 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- CUNNCKOPAWXYDX-SFECMWDFSA-N (NZ)-N-[(2Z)-2-hydroxyiminocyclohexylidene]hydroxylamine Chemical compound O\N=C/1\CCCC\C\1=N\O CUNNCKOPAWXYDX-SFECMWDFSA-N 0.000 description 10
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 10
- 229940093499 ethyl acetate Drugs 0.000 description 10
- 235000011150 stannous chloride Nutrition 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 229960003330 pentetic acid Drugs 0.000 description 9
- 101150041968 CDC13 gene Proteins 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 230000014759 maintenance of location Effects 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 239000011347 resin Substances 0.000 description 8
- 229920005989 resin Polymers 0.000 description 8
- 229910052713 technetium Inorganic materials 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 101001068640 Nicotiana tabacum Basic form of pathogenesis-related protein 1 Proteins 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 229940049953 phenylacetate Drugs 0.000 description 7
- GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical compound [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- YZEUHQHUFTYLPH-UHFFFAOYSA-N 2-nitroimidazole Chemical compound [O-][N+](=O)C1=NC=CN1 YZEUHQHUFTYLPH-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- 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 5
- ZISFIJBYCYVOAF-UHFFFAOYSA-N 2-(4-bromophenyl)-2-hydroxy-2-phenylacetic acid Chemical compound C=1C=C(Br)C=CC=1C(O)(C(=O)O)C1=CC=CC=C1 ZISFIJBYCYVOAF-UHFFFAOYSA-N 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- BVKJDOISYUXQKD-TZIWHRDSSA-N C1([C@](O)(C(=O)O)C=2C=C(C(I)=CC=2)[C@@H]2N3CCC(CC3)C2)=CC=CC=C1 Chemical compound C1([C@](O)(C(=O)O)C=2C=C(C(I)=CC=2)[C@@H]2N3CCC(CC3)C2)=CC=CC=C1 BVKJDOISYUXQKD-TZIWHRDSSA-N 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 239000001119 stannous chloride Substances 0.000 description 5
- AJSTXXYNEIHPMD-UHFFFAOYSA-N triethyl borate Chemical compound CCOB(OCC)OCC AJSTXXYNEIHPMD-UHFFFAOYSA-N 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- 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 4
- XMGZWGBXVLJOKE-UHFFFAOYSA-N acetic acid;toluene Chemical compound CC(O)=O.CC1=CC=CC=C1 XMGZWGBXVLJOKE-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 239000008139 complexing agent Substances 0.000 description 4
- 229910001873 dinitrogen Inorganic materials 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 4
- OBBCSXFCDPPXOL-UHFFFAOYSA-N misonidazole Chemical compound COCC(O)CN1C=CN=C1[N+]([O-])=O OBBCSXFCDPPXOL-UHFFFAOYSA-N 0.000 description 4
- 229950010514 misonidazole Drugs 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
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- MWEBNHUKQKORGU-UHFFFAOYSA-N [4-[[di(propan-2-yl)amino]methyl]phenyl]boronic acid Chemical compound CC(C)N(C(C)C)CC1=CC=C(B(O)O)C=C1 MWEBNHUKQKORGU-UHFFFAOYSA-N 0.000 description 1
- KXGLBKLYLCSKKJ-UHFFFAOYSA-N [4-[[ethyl(propan-2-yl)amino]methyl]phenyl]boronic acid Chemical compound CCN(C(C)C)CC1=CC=C(B(O)O)C=C1 KXGLBKLYLCSKKJ-UHFFFAOYSA-N 0.000 description 1
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- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
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- 239000011630 iodine Substances 0.000 description 1
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- 125000001810 isothiocyanato group Chemical group *N=C=S 0.000 description 1
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
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- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
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- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
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- WXBOMIKEWRRKBB-UHFFFAOYSA-N rhenium(iv) oxide Chemical class O=[Re]=O WXBOMIKEWRRKBB-UHFFFAOYSA-N 0.000 description 1
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- 238000000926 separation method Methods 0.000 description 1
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(I) nitrate Inorganic materials [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
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- DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 1
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- ANOBYBYXJXCGBS-UHFFFAOYSA-L stannous fluoride Chemical compound F[Sn]F ANOBYBYXJXCGBS-UHFFFAOYSA-L 0.000 description 1
- 229960002799 stannous fluoride Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
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- 125000001424 substituent group Chemical group 0.000 description 1
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- 210000003568 synaptosome Anatomy 0.000 description 1
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- FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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- 125000000858 thiocyanato group Chemical group *SC#N 0.000 description 1
- IUTCEZPPWBHGIX-UHFFFAOYSA-N tin(2+) Chemical compound [Sn+2] IUTCEZPPWBHGIX-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- LOIHSHVELSAXQN-UHFFFAOYSA-K trirhenium nonachloride Chemical compound Cl[Re](Cl)Cl LOIHSHVELSAXQN-UHFFFAOYSA-K 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
- A61K51/0478—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group complexes from non-cyclic ligands, e.g. EDTA, MAG3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0497—Organic compounds conjugates with a carrier being an organic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F13/00—Compounds containing elements of Groups 7 or 17 of the Periodic Table
- C07F13/005—Compounds without a metal-carbon linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL11417591A IL114175A (en) | 1990-01-18 | 1991-01-15 | Nitroheterocyclic boronic acid derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46688490A | 1990-01-18 | 1990-01-18 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL96946A0 IL96946A0 (en) | 1992-03-29 |
| IL96946A true IL96946A (he) | 1995-12-08 |
Family
ID=23853463
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9694691A IL96946A (he) | 1990-01-18 | 1991-01-15 | תולדות חומצה בורונית, שיטות וערכות לאבחנה המכילות אותן |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US5387409A (he) |
| EP (1) | EP0441491A1 (he) |
| JP (1) | JPH04212099A (he) |
| KR (1) | KR100191568B1 (he) |
| CN (3) | CN1034078C (he) |
| AU (2) | AU651076B2 (he) |
| CA (1) | CA2034042C (he) |
| FI (1) | FI910274A (he) |
| HU (1) | HU910155D0 (he) |
| IE (1) | IE910133A1 (he) |
| IL (1) | IL96946A (he) |
| MX (1) | MX24177A (he) |
| MY (1) | MY105482A (he) |
| NO (1) | NO910201L (he) |
| NZ (1) | NZ236789A (he) |
| PT (1) | PT96518B (he) |
| YU (1) | YU26691A (he) |
| ZA (1) | ZA91300B (he) |
Families Citing this family (63)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US5256394A (en) * | 1991-10-23 | 1993-10-26 | Boron Biologicals, Inc. | Radiological imaging method, and contrast media reagents therefor |
| US6359120B1 (en) | 1991-10-29 | 2002-03-19 | Bracco International B.V. | Rhenium and technetium complexes containing a hypoxia-localizing moiety |
| US5808091A (en) * | 1991-10-29 | 1998-09-15 | Bracco International B.V. | Rhenium and technetium complexes containing a hypoxia localizing moiety |
| FR2690443B1 (fr) * | 1992-04-10 | 1995-06-30 | Wallone Region | Marquage des hormones par le rhenium et le technetium. |
| US5608110A (en) * | 1993-06-15 | 1997-03-04 | Bracco International B.V. | Heteroatom-bearing ligands and metal complexes thereof |
| WO1995009844A1 (en) * | 1993-10-04 | 1995-04-13 | Board Of Regents, The University Of Texas System | Rapid synthesis and use of 18f-fluoromisonidazole and analogs |
| ES2114735T3 (es) * | 1994-01-12 | 1998-06-01 | Bracco Int Bv | Ligandos y complejos metalicos de los mismos. |
| EP0729363B1 (en) * | 1994-06-27 | 2003-02-19 | Neutron Therapies Inc. | Boron-containing hormone analogs and methods of their use in imaging or killing cells having hormone receptors |
| KR100430061B1 (ko) * | 2000-03-21 | 2004-05-03 | 재단법인 아산사회복지재단 | 글루코스 유도체에 방사성 동위원소가 표지된 착화합물 및이를 생산하기 위한 조성물이 포함된 키트 |
| US8489176B1 (en) | 2000-08-21 | 2013-07-16 | Spectrum Dynamics Llc | Radioactive emission detector equipped with a position tracking system and utilization thereof with medical systems and in medical procedures |
| US8909325B2 (en) * | 2000-08-21 | 2014-12-09 | Biosensors International Group, Ltd. | Radioactive emission detector equipped with a position tracking system and utilization thereof with medical systems and in medical procedures |
| US8565860B2 (en) * | 2000-08-21 | 2013-10-22 | Biosensors International Group, Ltd. | Radioactive emission detector equipped with a position tracking system |
| US7794693B2 (en) * | 2002-03-01 | 2010-09-14 | Bracco International B.V. | Targeting vector-phospholipid conjugates |
| US7211240B2 (en) * | 2002-03-01 | 2007-05-01 | Bracco International B.V. | Multivalent constructs for therapeutic and diagnostic applications |
| EP2301587B1 (en) | 2002-03-01 | 2014-06-25 | Dyax Corp. | KDR and VEGF/KDR binding peptides and their use in diagnosis |
| US7261876B2 (en) | 2002-03-01 | 2007-08-28 | Bracco International Bv | Multivalent constructs for therapeutic and diagnostic applications |
| US8623822B2 (en) | 2002-03-01 | 2014-01-07 | Bracco Suisse Sa | KDR and VEGF/KDR binding peptides and their use in diagnosis and therapy |
| CA2513044A1 (en) | 2002-03-01 | 2004-08-05 | Dyax Corp. | Kdr and vegf/kdr binding peptides and their use in diagnosis and therapy |
| US20040204646A1 (en) * | 2002-11-04 | 2004-10-14 | V-Target Technologies Ltd. | Intracorporeal-imaging head |
| US7226577B2 (en) | 2003-01-13 | 2007-06-05 | Bracco Imaging, S. P. A. | Gastrin releasing peptide compounds |
| US20050214859A1 (en) | 2003-03-03 | 2005-09-29 | Dyax Corp. | Peptides that specifically bind HGF receptor (cMet) and uses thereof |
| CA2783275A1 (en) * | 2003-07-24 | 2005-02-03 | Bracco Imaging S.P.A. | Stable radiopharmaceutical compositions and methods for their preparation |
| WO2005067383A2 (en) * | 2004-01-13 | 2005-07-28 | Spectrum Dynamics Llc | Multi-dimensional image reconstruction |
| US8571881B2 (en) | 2004-11-09 | 2013-10-29 | Spectrum Dynamics, Llc | Radiopharmaceutical dispensing, administration, and imaging |
| US8586932B2 (en) * | 2004-11-09 | 2013-11-19 | Spectrum Dynamics Llc | System and method for radioactive emission measurement |
| US7968851B2 (en) | 2004-01-13 | 2011-06-28 | Spectrum Dynamics Llc | Dynamic spect camera |
| WO2008010227A2 (en) * | 2006-07-19 | 2008-01-24 | Spectrum Dynamics Llc | Imaging protocols |
| US9470801B2 (en) * | 2004-01-13 | 2016-10-18 | Spectrum Dynamics Llc | Gating with anatomically varying durations |
| WO2006051531A2 (en) * | 2004-11-09 | 2006-05-18 | Spectrum Dynamics Llc | Radioimaging |
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| EP1824520B1 (en) * | 2004-11-17 | 2016-04-27 | Biosensors International Group, Ltd. | Methods of detecting prostate cancer |
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| US8894974B2 (en) * | 2006-05-11 | 2014-11-25 | Spectrum Dynamics Llc | Radiopharmaceuticals for diagnosis and therapy |
| US8610075B2 (en) | 2006-11-13 | 2013-12-17 | Biosensors International Group Ltd. | Radioimaging applications of and novel formulations of teboroxime |
| JP5364589B2 (ja) | 2006-12-11 | 2013-12-11 | ブラッコ・イメージング・ソシエタ・ペル・アチオニ | 診断および治療適用用フィブリン結合ペプチドコンジュゲート |
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| US8521253B2 (en) * | 2007-10-29 | 2013-08-27 | Spectrum Dynamics Llc | Prostate imaging |
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|---|---|---|---|---|
| US3369121A (en) | 1966-04-06 | 1968-02-13 | Squibb & Sons Inc | Radioactive package and container therefor |
| US3920995A (en) | 1973-05-04 | 1975-11-18 | Squibb & Sons Inc | Radioactive material generator |
| US4431627A (en) * | 1980-06-03 | 1984-02-14 | Research Corporation | Gamma-emitting receptor-binding 3-quinuclidinyl glycolates; methods of preparation thereof and imaging and assay methods utilizing same |
| US4705849A (en) * | 1985-04-15 | 1987-11-10 | E. R. Squibb & Sons, Inc. | Boronic acid adducts of technetium-99m dioxime complexes |
| US4871836A (en) | 1987-10-13 | 1989-10-03 | E. R. Squibb & Sons, Inc. | Boronic acid adducts of rhenium and radioactive isotopes of rhenium dioxime complexes |
| CN1022562C (zh) * | 1989-04-08 | 1993-10-27 | 中国人民解放军第二军医大学 | 一种消瘤药——甲硝唑氨酸的合成方法 |
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1991
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- 1991-01-14 MY MYPI91000058A patent/MY105482A/en unknown
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- 1991-01-16 AU AU69385/91A patent/AU651076B2/en not_active Ceased
- 1991-01-16 NZ NZ236789A patent/NZ236789A/en unknown
- 1991-01-16 IE IE013391A patent/IE910133A1/en unknown
- 1991-01-17 MX MX2417791A patent/MX24177A/es unknown
- 1991-01-17 NO NO91910201A patent/NO910201L/no unknown
- 1991-01-17 HU HU91155A patent/HU910155D0/hu unknown
- 1991-01-18 YU YU26691A patent/YU26691A/sh unknown
- 1991-01-18 CN CN91101146A patent/CN1034078C/zh not_active Expired - Fee Related
- 1991-01-18 JP JP3019465A patent/JPH04212099A/ja active Pending
- 1991-01-18 PT PT96518A patent/PT96518B/pt not_active IP Right Cessation
- 1991-01-18 EP EP91300414A patent/EP0441491A1/en not_active Ceased
- 1991-01-18 FI FI910274A patent/FI910274A/fi not_active Application Discontinuation
- 1991-01-18 KR KR1019910000787A patent/KR100191568B1/ko not_active IP Right Cessation
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1992
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1994
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1995
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| CN1111621A (zh) | 1995-11-15 |
| IL96946A0 (en) | 1992-03-29 |
| NZ236789A (en) | 1995-03-28 |
| AU651076B2 (en) | 1994-07-14 |
| EP0441491A1 (en) | 1991-08-14 |
| AU6938591A (en) | 1991-07-25 |
| CN1034078C (zh) | 1997-02-19 |
| CN1120437A (zh) | 1996-04-17 |
| KR100191568B1 (ko) | 1999-06-15 |
| MY105482A (en) | 1994-10-31 |
| FI910274A (fi) | 1991-07-19 |
| KR910014385A (ko) | 1991-08-31 |
| YU26691A (sh) | 1994-05-10 |
| NO910201L (no) | 1991-07-19 |
| JPH04212099A (ja) | 1992-08-03 |
| PT96518B (pt) | 1998-06-30 |
| NO910201D0 (no) | 1991-01-17 |
| CA2034042A1 (en) | 1991-07-19 |
| ZA91300B (en) | 1991-11-27 |
| US5387409A (en) | 1995-02-07 |
| HU910155D0 (en) | 1991-08-28 |
| CN1054070A (zh) | 1991-08-28 |
| MX24177A (es) | 1993-12-01 |
| IE910133A1 (en) | 1991-07-31 |
| CA2034042C (en) | 1999-08-17 |
| AU7914794A (en) | 1995-02-16 |
| PT96518A (pt) | 1991-10-15 |
| FI910274A0 (fi) | 1991-01-18 |
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