JP2004500321A - 金属錯体を含む薬学的組成物 - Google Patents
金属錯体を含む薬学的組成物 Download PDFInfo
- Publication number
- JP2004500321A JP2004500321A JP2000606604A JP2000606604A JP2004500321A JP 2004500321 A JP2004500321 A JP 2004500321A JP 2000606604 A JP2000606604 A JP 2000606604A JP 2000606604 A JP2000606604 A JP 2000606604A JP 2004500321 A JP2004500321 A JP 2004500321A
- Authority
- JP
- Japan
- Prior art keywords
- bis
- ruthenium
- iii
- methyl
- acetonitrile
- 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.)
- Withdrawn
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 39
- 229910052751 metal Inorganic materials 0.000 title description 19
- 239000002184 metal Substances 0.000 title description 19
- 239000000203 mixture Substances 0.000 claims abstract description 130
- -1 halide Ion Chemical class 0.000 claims abstract description 77
- 239000003446 ligand Substances 0.000 claims abstract description 71
- 150000001875 compounds Chemical class 0.000 claims abstract description 60
- 150000001768 cations Chemical class 0.000 claims abstract description 19
- 229910021645 metal ion Inorganic materials 0.000 claims abstract description 12
- 230000000737 periodic effect Effects 0.000 claims abstract description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 353
- 229910052757 nitrogen Inorganic materials 0.000 claims description 195
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 161
- 229910052707 ruthenium Inorganic materials 0.000 claims description 97
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 91
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 claims description 82
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 80
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 52
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 34
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 32
- 201000010099 disease Diseases 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- BPEVHDGLPIIAGH-UHFFFAOYSA-N ruthenium(3+) Chemical compound [Ru+3] BPEVHDGLPIIAGH-UHFFFAOYSA-N 0.000 claims description 32
- 229910001868 water Inorganic materials 0.000 claims description 32
- XPCTZQVDEJYUGT-UHFFFAOYSA-N 3-hydroxy-2-methyl-4-pyrone Chemical compound CC=1OC=CC(=O)C=1O XPCTZQVDEJYUGT-UHFFFAOYSA-N 0.000 claims description 26
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 26
- YAYGSLOSTXKUBW-UHFFFAOYSA-N ruthenium(2+) Chemical compound [Ru+2] YAYGSLOSTXKUBW-UHFFFAOYSA-N 0.000 claims description 26
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 25
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
- ITWBWJFEJCHKSN-UHFFFAOYSA-N 1,4,7-triazonane Chemical compound C1CNCCNCCN1 ITWBWJFEJCHKSN-UHFFFAOYSA-N 0.000 claims description 20
- 239000003642 reactive oxygen metabolite Substances 0.000 claims description 20
- ARSLWGHFZUGJTK-UHFFFAOYSA-K ruthenium(3+);trifluoromethanesulfonate Chemical compound [Ru+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F ARSLWGHFZUGJTK-UHFFFAOYSA-K 0.000 claims description 20
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000004429 atom Chemical group 0.000 claims description 16
- MDYOLVRUBBJPFM-UHFFFAOYSA-N tropolone Chemical compound OC1=CC=CC=CC1=O MDYOLVRUBBJPFM-UHFFFAOYSA-N 0.000 claims description 16
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- 125000000129 anionic group Chemical group 0.000 claims description 14
- 230000007935 neutral effect Effects 0.000 claims description 14
- HYMLWHLQFGRFIY-UHFFFAOYSA-N Maltol Natural products CC1OC=CC(=O)C1=O HYMLWHLQFGRFIY-UHFFFAOYSA-N 0.000 claims description 13
- 229940043353 maltol Drugs 0.000 claims description 13
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 238000012261 overproduction Methods 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- DHCWLIOIJZJFJE-UHFFFAOYSA-L dichlororuthenium Chemical compound Cl[Ru]Cl DHCWLIOIJZJFJE-UHFFFAOYSA-L 0.000 claims description 11
- 229910052700 potassium Inorganic materials 0.000 claims description 11
- 239000011591 potassium Substances 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 239000011593 sulfur Substances 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 150000004820 halides Chemical class 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 claims description 10
- MDAXKAUIABOHTD-UHFFFAOYSA-N 1,4,8,11-tetraazacyclotetradecane Chemical compound C1CNCCNCCCNCCNC1 MDAXKAUIABOHTD-UHFFFAOYSA-N 0.000 claims description 9
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 8
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims description 8
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 7
- JIXOCHSERUXVMW-UHFFFAOYSA-M chlororuthenium Chemical compound [Ru]Cl JIXOCHSERUXVMW-UHFFFAOYSA-M 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- IFQUWYZCAGRUJN-UHFFFAOYSA-N ethylenediaminediacetic acid Chemical compound OC(=O)CNCCNCC(O)=O IFQUWYZCAGRUJN-UHFFFAOYSA-N 0.000 claims description 7
- 230000003647 oxidation Effects 0.000 claims description 7
- 238000007254 oxidation reaction Methods 0.000 claims description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 claims description 7
- 230000004614 tumor growth Effects 0.000 claims description 7
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 6
- 150000007942 carboxylates Chemical class 0.000 claims description 6
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 5
- 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 claims description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 229910052762 osmium Inorganic materials 0.000 claims description 5
- 229960003330 pentetic acid Drugs 0.000 claims description 5
- 229910052703 rhodium Inorganic materials 0.000 claims description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- BOUNYCSDIFNPHL-UHFFFAOYSA-N 2-[2-[2-[bis(carboxymethyl)amino]ethylsulfanyl]ethyl-(carboxymethyl)amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)CCSCCN(CC(O)=O)CC(O)=O BOUNYCSDIFNPHL-UHFFFAOYSA-N 0.000 claims description 4
- BDDLHHRCDSJVKV-UHFFFAOYSA-N 7028-40-2 Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O BDDLHHRCDSJVKV-UHFFFAOYSA-N 0.000 claims description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 4
- 241000191368 Chlorobi Species 0.000 claims description 4
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 4
- LIRCFGBNQPWVRY-UHFFFAOYSA-K aluminum;2-methyl-4-oxopyran-3-olate Chemical compound [Al+3].CC=1OC=CC(=O)C=1[O-].CC=1OC=CC(=O)C=1[O-].CC=1OC=CC(=O)C=1[O-] LIRCFGBNQPWVRY-UHFFFAOYSA-K 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 229940081066 picolinic acid Drugs 0.000 claims description 4
- PWEBUXCTKOWPCW-UHFFFAOYSA-N squaric acid Chemical compound OC1=C(O)C(=O)C1=O PWEBUXCTKOWPCW-UHFFFAOYSA-N 0.000 claims description 4
- URDCARMUOSMFFI-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(2-hydroxyethyl)amino]acetic acid Chemical compound OCCN(CC(O)=O)CCN(CC(O)=O)CC(O)=O URDCARMUOSMFFI-UHFFFAOYSA-N 0.000 claims description 3
- 229910052804 chromium Inorganic materials 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 3
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 claims description 3
- 229960004705 kojic acid Drugs 0.000 claims description 3
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 claims description 3
- 229910052748 manganese Inorganic materials 0.000 claims description 3
- JRNGUTKWMSBIBF-UHFFFAOYSA-N naphthalene-2,3-diol Chemical compound C1=CC=C2C=C(O)C(O)=CC2=C1 JRNGUTKWMSBIBF-UHFFFAOYSA-N 0.000 claims description 3
- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 claims description 3
- 235000006408 oxalic acid Nutrition 0.000 claims description 3
- 150000002978 peroxides Chemical class 0.000 claims description 3
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- NRMQMTQTYONMFY-UHFFFAOYSA-N morpholine-4-carbodithioic acid Chemical compound SC(=S)N1CCOCC1 NRMQMTQTYONMFY-UHFFFAOYSA-N 0.000 claims description 2
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical group O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 claims description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 229910052702 rhenium Inorganic materials 0.000 claims description 2
- 241000894007 species Species 0.000 claims description 2
- OUDSFQBUEBFSPS-UHFFFAOYSA-N ethylenediaminetriacetic acid Chemical compound OC(=O)CNCCN(CC(O)=O)CC(O)=O OUDSFQBUEBFSPS-UHFFFAOYSA-N 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims 1
- BYRZXNYYFKCSHR-UHFFFAOYSA-M chlororuthenium(2+) Chemical compound [Ru+2]Cl BYRZXNYYFKCSHR-UHFFFAOYSA-M 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- CMFNMSMUKZHDEY-UHFFFAOYSA-N peroxynitrous acid Chemical compound OON=O CMFNMSMUKZHDEY-UHFFFAOYSA-N 0.000 claims 1
- JFFVXCPVHOPULP-UHFFFAOYSA-L ruthenium(2+);trifluoromethanesulfonate Chemical compound [Ru+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F JFFVXCPVHOPULP-UHFFFAOYSA-L 0.000 claims 1
- 229910052723 transition metal Inorganic materials 0.000 claims 1
- 150000003624 transition metals Chemical class 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 176
- 239000000243 solution Substances 0.000 description 139
- 238000000034 method Methods 0.000 description 106
- 239000007787 solid Substances 0.000 description 101
- 238000002360 preparation method Methods 0.000 description 86
- 239000000047 product Substances 0.000 description 86
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 63
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
- 239000000741 silica gel Substances 0.000 description 51
- 229910002027 silica gel Inorganic materials 0.000 description 51
- 239000002904 solvent Substances 0.000 description 51
- 238000004440 column chromatography Methods 0.000 description 49
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 47
- 239000011541 reaction mixture Substances 0.000 description 47
- 239000003921 oil Substances 0.000 description 44
- 235000019198 oils Nutrition 0.000 description 44
- 238000003786 synthesis reaction Methods 0.000 description 39
- 238000004458 analytical method Methods 0.000 description 37
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 37
- 238000001914 filtration Methods 0.000 description 34
- 206010028980 Neoplasm Diseases 0.000 description 32
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 32
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
- 238000002329 infrared spectrum Methods 0.000 description 30
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 29
- 238000010992 reflux Methods 0.000 description 29
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 230000015572 biosynthetic process Effects 0.000 description 25
- 239000000706 filtrate Substances 0.000 description 25
- 239000002244 precipitate Substances 0.000 description 23
- 238000003756 stirring Methods 0.000 description 23
- 238000012360 testing method Methods 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 21
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 20
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 19
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 18
- 229910000027 potassium carbonate Inorganic materials 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 229910002651 NO3 Inorganic materials 0.000 description 15
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 15
- 239000012043 crude product Substances 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
- 239000012230 colorless oil Substances 0.000 description 14
- 239000000284 extract Substances 0.000 description 14
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 14
- 239000000725 suspension Substances 0.000 description 13
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 13
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 201000011510 cancer Diseases 0.000 description 10
- DRGAZIDRYFYHIJ-UHFFFAOYSA-N 2,2':6',2''-terpyridine Chemical compound N1=CC=CC=C1C1=CC=CC(C=2N=CC=CC=2)=N1 DRGAZIDRYFYHIJ-UHFFFAOYSA-N 0.000 description 9
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 9
- 239000012327 Ruthenium complex Substances 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 239000008367 deionised water Substances 0.000 description 9
- 229910021641 deionized water Inorganic materials 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-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
- 125000002091 cationic group Chemical group 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
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- LCZVKKUAUWQDPX-UHFFFAOYSA-N tert-butyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]ethyl]amino]acetate Chemical compound CC(=O)OC1=CC=CC=C1CN(CC(=O)OC(C)(C)C)CCN(CC(=O)OC(C)(C)C)CC1=CC=CC=C1OC(C)=O LCZVKKUAUWQDPX-UHFFFAOYSA-N 0.000 description 1
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- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000010981 turquoise Substances 0.000 description 1
- YXZRCLVVNRLPTP-UHFFFAOYSA-J turquoise blue Chemical compound [Na+].[Na+].[Na+].[Na+].[Cu+2].NC1=NC(Cl)=NC(NC=2C=C(NS(=O)(=O)C3=CC=4C(=C5NC=4NC=4[N-]C(=C6C=CC(=CC6=4)S([O-])(=O)=O)NC=4NC(=C6C=C(C=CC6=4)S([O-])(=O)=O)NC=4[N-]C(=C6C=CC(=CC6=4)S([O-])(=O)=O)N5)C=C3)C(=CC=2)S([O-])(=O)=O)=N1 YXZRCLVVNRLPTP-UHFFFAOYSA-J 0.000 description 1
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Images
Classifications
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- 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
- C07F19/00—Metal compounds according to more than one of main groups C07F1/00 - C07F17/00
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium compounds without a metal-carbon linkage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/28—Compounds containing heavy metals
- A61K31/295—Iron group metal compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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| US12516699P | 1999-03-19 | 1999-03-19 | |
| PCT/CA2000/000294 WO2000056743A1 (en) | 1999-03-19 | 2000-03-17 | Pharmaceutical compositions comprising metal complexes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2004500321A true JP2004500321A (ja) | 2004-01-08 |
| JP2004500321A5 JP2004500321A5 (enExample) | 2004-12-24 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| JP2000606604A Withdrawn JP2004500321A (ja) | 1999-03-19 | 2000-03-17 | 金属錯体を含む薬学的組成物 |
Country Status (15)
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|---|---|
| US (1) | US20020049190A1 (enExample) |
| EP (1) | EP1163247A1 (enExample) |
| JP (1) | JP2004500321A (enExample) |
| KR (1) | KR20010112343A (enExample) |
| CN (1) | CN1391577A (enExample) |
| AU (1) | AU3268500A (enExample) |
| BR (1) | BR0011678A (enExample) |
| CA (1) | CA2367282A1 (enExample) |
| CZ (1) | CZ20013307A3 (enExample) |
| HU (1) | HUP0400457A2 (enExample) |
| IL (1) | IL145290A0 (enExample) |
| MX (1) | MXPA01009410A (enExample) |
| NO (1) | NO20014526L (enExample) |
| PL (1) | PL356683A1 (enExample) |
| WO (1) | WO2000056743A1 (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007102286A1 (ja) | 2006-03-08 | 2007-09-13 | Kyorin Pharmaceutical Co., Ltd. | アミノアセチルピロリジンカルボニトリル誘導体の製造方法およびその製造中間体 |
| WO2008114857A1 (ja) | 2007-03-22 | 2008-09-25 | Kyorin Pharmaceutical Co., Ltd. | アミノアセチルピロリジンカルボニトリル誘導体の製造方法 |
| JP2013079237A (ja) * | 2005-12-21 | 2013-05-02 | F Hoffmann-La Roche Ag | レドックスメディエータ |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ514736A (en) | 1999-04-13 | 2004-01-30 | Anormed Inc | Process for preparing amine platinum complexes |
| JP4227701B2 (ja) * | 1999-05-25 | 2009-02-18 | 中部キレスト株式会社 | ジエチレントリアミン五酢酸ルテニウム二アンモニウム塩またはその水和物およびその製法 |
| US6489638B2 (en) * | 2000-06-23 | 2002-12-03 | Semiconductor Energy Laboratory Co., Ltd. | Light emitting device |
| US6894049B1 (en) | 2000-10-04 | 2005-05-17 | Anormed, Inc. | Platinum complexes as antitumor agents |
| US20020072512A1 (en) * | 2000-12-08 | 2002-06-13 | Metaphore Pharmaceuticals, Inc | Method of preventing and treating HIV-mediated central nervous system damage |
| GB0111872D0 (en) | 2001-05-15 | 2001-07-04 | Northwick Park Inst For Medica | Therapeutic agents and methods |
| BR0307420A (pt) | 2002-02-04 | 2004-12-21 | Werner Haas | Compostos, composições farmacêuticas e métodos para impedir e/ou tratar doença em mamìfero |
| GB2395432B (en) * | 2002-11-20 | 2005-09-14 | Northwick Park Inst For Medica | Therapeutic delivery of carbon monoxide to extracorporeal and isolated organs |
| GB2395431A (en) * | 2002-11-20 | 2004-05-26 | Northwick Park Inst For Medica | Combination of a metal carbonyl compound and a guanylate cyclase stimulant or stabilizer for the therapeutic delivery of carbon monoxide |
| ES2390457T3 (es) * | 2003-08-04 | 2012-11-13 | Johnson & Johnson Consumer Companies, Inc. | Métodos para el tratamiento de enfermedades dermatológicas |
| AU2005210285B2 (en) * | 2004-02-05 | 2008-01-24 | Kyorin Pharmaceutical Co., Ltd. | Bicycloester derivative |
| FR2873037B1 (fr) * | 2004-07-13 | 2008-04-11 | Univ Pasteur | Methodes et compositions pour le traitement de cancers |
| GB0601394D0 (en) | 2006-01-24 | 2006-03-01 | Hemocorm Ltd | Therapeutic delivery of carbon monoxide |
| DK2032701T3 (da) | 2006-06-23 | 2014-02-10 | Alethia Biotherapeutics Inc | Polynukleotider og polypeptider, der er inddraget i cancer |
| WO2008038305A2 (en) * | 2006-09-26 | 2008-04-03 | Jegannathan Srinivas | Therapeutical formulation comprising a thiazolidinedione and a nitric oxide scavenger. |
| CA2740900C (en) | 2008-11-03 | 2019-09-24 | Alethia Biotherapeutics Inc. | Antibodies that specifically block the biological activity of a tumor antigen |
| DE102010014412A1 (de) | 2010-04-08 | 2012-04-19 | Friedrich-Schiller-Universität Jena | Verwendung von zweikernigen Eisenkomplexen mit schwefelhaltigen Liganden als pharmakologische Wirkstoffe |
| DE102010014411A1 (de) | 2010-04-08 | 2011-10-13 | Friedrich-Schiller-Universität Jena | Kohlenmonoxid und Eisen freisetzende Moleküle, deren Verwendung und Verfahren zu deren Herstellung |
| HUE045943T2 (hu) | 2011-03-31 | 2020-02-28 | Adc Therapeutics Sa | Veseasszociált antigén 1 és antigénkötõ fragmensei elleni antitestek |
| WO2012145520A2 (en) | 2011-04-19 | 2012-10-26 | Alfama, Inc. | Carbon monoxide releasing molecules and uses thereof |
| ES2628634T3 (es) | 2011-07-21 | 2017-08-03 | Alfama, Inc. | Moléculas liberadoras de monóxido de carbono-rutenio y usos de las mismas |
| NZ625758A (en) | 2012-01-09 | 2016-05-27 | Alethia Biotherapeutics Inc | Method for treating breast cancer |
| DE102012004132A1 (de) | 2012-02-29 | 2013-08-29 | Friedrich-Schiller-Universität Jena | Kohlenstoffmonoxid freisetzende Materialien und deren Verwendung |
| DE102014008537A1 (de) | 2014-06-04 | 2015-12-17 | Friedrich-Schiller-Universität Jena | Wasserlösliche manganbasierte Kohlenstoffmonoxid freisetzende Moleküle, deren Verwendung und Verfahren zu deren Herstellung |
| WO2016065435A2 (en) * | 2014-10-30 | 2016-05-06 | Katholieke Universiteit Leuven | Methods for low temperature fluorine-18 radiolabeling of biomolecules |
| CN113429456B (zh) * | 2021-06-11 | 2022-05-31 | 首都医科大学 | 多肽衍生物钌类络合物及其制备方法和应用 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4721669A (en) * | 1985-01-18 | 1988-01-26 | The Trustees Of Columbia University In The City Of New York | Chemical probes for left-handed DNA and chiral metal complexes as Z-specific anti-tumor agents |
| US5112974A (en) * | 1985-01-18 | 1992-05-12 | The Trustees Of Columbia University In The City Of New York | Mixed ligand complexes and uses thereof as binding agents to DNA |
| GB9317686D0 (en) * | 1993-08-25 | 1993-10-13 | Johnson Matthey Plc | Pharmaceutical compositions |
| SE9703396D0 (sv) * | 1997-09-19 | 1997-09-19 | Lincoln | Binuclear complex |
-
2000
- 2000-03-17 AU AU32685/00A patent/AU3268500A/en not_active Abandoned
- 2000-03-17 IL IL14529000A patent/IL145290A0/xx unknown
- 2000-03-17 US US09/527,450 patent/US20020049190A1/en not_active Abandoned
- 2000-03-17 BR BR0011678-5A patent/BR0011678A/pt not_active Application Discontinuation
- 2000-03-17 HU HU0400457A patent/HUP0400457A2/hu unknown
- 2000-03-17 EP EP00910468A patent/EP1163247A1/en not_active Withdrawn
- 2000-03-17 MX MXPA01009410A patent/MXPA01009410A/es unknown
- 2000-03-17 PL PL00356683A patent/PL356683A1/xx not_active Application Discontinuation
- 2000-03-17 JP JP2000606604A patent/JP2004500321A/ja not_active Withdrawn
- 2000-03-17 WO PCT/CA2000/000294 patent/WO2000056743A1/en not_active Ceased
- 2000-03-17 CN CN00806748A patent/CN1391577A/zh active Pending
- 2000-03-17 KR KR1020017011819A patent/KR20010112343A/ko not_active Withdrawn
- 2000-03-17 CZ CZ20013307A patent/CZ20013307A3/cs unknown
- 2000-03-17 CA CA002367282A patent/CA2367282A1/en not_active Abandoned
-
2001
- 2001-09-18 NO NO20014526A patent/NO20014526L/no unknown
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013079237A (ja) * | 2005-12-21 | 2013-05-02 | F Hoffmann-La Roche Ag | レドックスメディエータ |
| WO2007102286A1 (ja) | 2006-03-08 | 2007-09-13 | Kyorin Pharmaceutical Co., Ltd. | アミノアセチルピロリジンカルボニトリル誘導体の製造方法およびその製造中間体 |
| WO2008114857A1 (ja) | 2007-03-22 | 2008-09-25 | Kyorin Pharmaceutical Co., Ltd. | アミノアセチルピロリジンカルボニトリル誘導体の製造方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| IL145290A0 (en) | 2002-06-30 |
| CA2367282A1 (en) | 2000-09-28 |
| EP1163247A1 (en) | 2001-12-19 |
| NO20014526L (no) | 2001-10-16 |
| WO2000056743A1 (en) | 2000-09-28 |
| CZ20013307A3 (cs) | 2002-05-15 |
| PL356683A1 (en) | 2004-06-28 |
| HUP0400457A2 (hu) | 2004-05-28 |
| MXPA01009410A (es) | 2003-06-06 |
| NO20014526D0 (no) | 2001-09-18 |
| AU3268500A (en) | 2000-10-09 |
| KR20010112343A (ko) | 2001-12-20 |
| CN1391577A (zh) | 2003-01-15 |
| US20020049190A1 (en) | 2002-04-25 |
| BR0011678A (pt) | 2002-02-26 |
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