AU3268500A - Pharmaceutical compositions comprising metal complexes - Google Patents
Pharmaceutical compositions comprising metal complexes Download PDFInfo
- Publication number
- AU3268500A AU3268500A AU32685/00A AU3268500A AU3268500A AU 3268500 A AU3268500 A AU 3268500A AU 32685/00 A AU32685/00 A AU 32685/00A AU 3268500 A AU3268500 A AU 3268500A AU 3268500 A AU3268500 A AU 3268500A
- Authority
- AU
- Australia
- Prior art keywords
- ruthenium
- bis
- amd
- iii
- methyl
- 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.)
- Abandoned
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 49
- 229910052751 metal Inorganic materials 0.000 title description 20
- 239000002184 metal Substances 0.000 title description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 436
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 181
- 239000000203 mixture Substances 0.000 claims description 133
- 229910052707 ruthenium Inorganic materials 0.000 claims description 115
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 112
- 238000000034 method Methods 0.000 claims description 102
- -1 pseudohalide ion Chemical class 0.000 claims description 92
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 90
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 claims description 87
- 239000003446 ligand Substances 0.000 claims description 80
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 76
- 229910052757 nitrogen Inorganic materials 0.000 claims description 72
- BPEVHDGLPIIAGH-UHFFFAOYSA-N ruthenium(3+) Chemical compound [Ru+3] BPEVHDGLPIIAGH-UHFFFAOYSA-N 0.000 claims description 66
- 150000001875 compounds Chemical class 0.000 claims description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 49
- 201000010099 disease Diseases 0.000 claims description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
- YAYGSLOSTXKUBW-UHFFFAOYSA-N ruthenium(2+) Chemical compound [Ru+2] YAYGSLOSTXKUBW-UHFFFAOYSA-N 0.000 claims description 36
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 35
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 34
- 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 33
- 229910001868 water Inorganic materials 0.000 claims description 33
- 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 32
- ITWBWJFEJCHKSN-UHFFFAOYSA-N 1,4,7-triazonane Chemical compound C1CNCCNCCN1 ITWBWJFEJCHKSN-UHFFFAOYSA-N 0.000 claims description 30
- XPCTZQVDEJYUGT-UHFFFAOYSA-N 3-hydroxy-2-methyl-4-pyrone Chemical compound CC=1OC=CC(=O)C=1O XPCTZQVDEJYUGT-UHFFFAOYSA-N 0.000 claims description 30
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 30
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 125000004429 atom Chemical group 0.000 claims description 23
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 21
- 125000000129 anionic group Chemical group 0.000 claims description 19
- 150000001768 cations Chemical group 0.000 claims description 19
- 239000003642 reactive oxygen metabolite Substances 0.000 claims description 19
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 18
- 230000007935 neutral effect Effects 0.000 claims description 18
- MDYOLVRUBBJPFM-UHFFFAOYSA-N tropolone Chemical compound OC1=CC=CC=CC1=O MDYOLVRUBBJPFM-UHFFFAOYSA-N 0.000 claims description 18
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 229910052700 potassium Inorganic materials 0.000 claims description 16
- 239000011591 potassium Substances 0.000 claims description 16
- HYMLWHLQFGRFIY-UHFFFAOYSA-N Maltol Natural products CC1OC=CC(=O)C1=O HYMLWHLQFGRFIY-UHFFFAOYSA-N 0.000 claims description 15
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 150000002148 esters Chemical class 0.000 claims description 15
- 229940043353 maltol Drugs 0.000 claims description 15
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 14
- 230000000737 periodic effect Effects 0.000 claims description 14
- MDAXKAUIABOHTD-UHFFFAOYSA-N 1,4,8,11-tetraazacyclotetradecane Chemical compound C1CNCCNCCCNCCNC1 MDAXKAUIABOHTD-UHFFFAOYSA-N 0.000 claims description 13
- 238000012261 overproduction Methods 0.000 claims description 13
- JIXOCHSERUXVMW-UHFFFAOYSA-M chlororuthenium Chemical compound [Ru]Cl JIXOCHSERUXVMW-UHFFFAOYSA-M 0.000 claims description 12
- 229910021645 metal ion Inorganic materials 0.000 claims description 12
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims description 12
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- 239000005864 Sulphur Substances 0.000 claims description 11
- DHCWLIOIJZJFJE-UHFFFAOYSA-L dichlororuthenium Chemical compound Cl[Ru]Cl DHCWLIOIJZJFJE-UHFFFAOYSA-L 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 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 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 10
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 10
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 claims description 10
- 150000004820 halides Chemical class 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 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 9
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 8
- IFQUWYZCAGRUJN-UHFFFAOYSA-N ethylenediaminediacetic acid Chemical compound OC(=O)CNCCNCC(O)=O IFQUWYZCAGRUJN-UHFFFAOYSA-N 0.000 claims description 8
- 150000002500 ions Chemical class 0.000 claims description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 7
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 7
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 7
- 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 7
- 229910052762 osmium Inorganic materials 0.000 claims description 7
- 230000003647 oxidation Effects 0.000 claims description 7
- 238000007254 oxidation reaction Methods 0.000 claims description 7
- 230000004614 tumor growth Effects 0.000 claims description 7
- 241000191368 Chlorobi Species 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
- 241001465754 Metazoa Species 0.000 claims description 6
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 6
- 150000001356 alkyl thiols Chemical class 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
- 239000003814 drug Substances 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 6
- 229960003330 pentetic acid Drugs 0.000 claims description 6
- 229940081066 picolinic acid Drugs 0.000 claims description 6
- 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 5
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 5
- 239000012327 Ruthenium complex Substances 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- OUDSFQBUEBFSPS-UHFFFAOYSA-N ethylenediaminetriacetic acid Chemical compound OC(=O)CNCCN(CC(O)=O)CC(O)=O OUDSFQBUEBFSPS-UHFFFAOYSA-N 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 5
- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 claims description 5
- 229910052703 rhodium Inorganic materials 0.000 claims description 5
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 4
- OTBHHUPVCYLGQO-UHFFFAOYSA-N bis(3-aminopropyl)amine Chemical compound NCCCNCCCN OTBHHUPVCYLGQO-UHFFFAOYSA-N 0.000 claims description 4
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims description 4
- 125000000267 glycino group Chemical group [H]N([*])C([H])([H])C(=O)O[H] 0.000 claims description 4
- 229910052720 vanadium Inorganic materials 0.000 claims description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 claims description 3
- 241000282412 Homo Species 0.000 claims description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000004171 alkoxy aryl group Chemical group 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 3
- 125000005189 alkyl hydroxy group Chemical group 0.000 claims description 3
- 235000001014 amino acid Nutrition 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 150000003931 anilides Chemical class 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 150000003857 carboxamides Chemical class 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
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 229910052748 manganese Inorganic materials 0.000 claims description 3
- FZERHIULMFGESH-UHFFFAOYSA-N methylenecarboxanilide Natural products CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 claims description 3
- HCIIFBHDBOCSAF-UHFFFAOYSA-N octaethylporphyrin Chemical compound N1C(C=C2C(=C(CC)C(C=C3C(=C(CC)C(=C4)N3)CC)=N2)CC)=C(CC)C(CC)=C1C=C1C(CC)=C(CC)C4=N1 HCIIFBHDBOCSAF-UHFFFAOYSA-N 0.000 claims description 3
- 235000006408 oxalic acid Nutrition 0.000 claims description 3
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical group O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 229910052702 rhenium Inorganic materials 0.000 claims description 3
- STWARMWRDXFBIE-UHFFFAOYSA-N ruthenium(2+);dihydrate Chemical compound O.O.[Ru+2] STWARMWRDXFBIE-UHFFFAOYSA-N 0.000 claims description 3
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 claims description 3
- PWEBUXCTKOWPCW-UHFFFAOYSA-N squaric acid Chemical compound OC1=C(O)C(=O)C1=O PWEBUXCTKOWPCW-UHFFFAOYSA-N 0.000 claims description 3
- 229910021653 sulphate ion Inorganic materials 0.000 claims description 3
- 150000003573 thiols Chemical class 0.000 claims description 3
- 229910001428 transition metal ion Inorganic materials 0.000 claims description 3
- CYJYKTMBMMYRHR-UHFFFAOYSA-N acetic acid;1,4,7-triazonane Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.C1CNCCNCCN1 CYJYKTMBMMYRHR-UHFFFAOYSA-N 0.000 claims description 2
- DTSDBGVDESRKKD-UHFFFAOYSA-N n'-(2-aminoethyl)propane-1,3-diamine Chemical compound NCCCNCCN DTSDBGVDESRKKD-UHFFFAOYSA-N 0.000 claims description 2
- 125000002577 pseudohalo group Chemical group 0.000 claims description 2
- HYNKQSJXYRFXDX-UHFFFAOYSA-L ruthenium(3+) 2,2,2-trifluoroacetate Chemical compound [Ru+3].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F HYNKQSJXYRFXDX-UHFFFAOYSA-L 0.000 claims description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 3
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- 150000004683 dihydrates Chemical class 0.000 claims 1
- BYNZKLMEELCCLR-UHFFFAOYSA-L ruthenium(2+);diperchlorate Chemical compound [Ru+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O BYNZKLMEELCCLR-UHFFFAOYSA-L 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 192
- 239000000243 solution Substances 0.000 description 139
- 239000007787 solid Substances 0.000 description 98
- 238000002360 preparation method Methods 0.000 description 89
- 239000000047 product Substances 0.000 description 85
- 238000005481 NMR spectroscopy Methods 0.000 description 84
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 77
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 68
- 239000000741 silica gel Substances 0.000 description 56
- 229910002027 silica gel Inorganic materials 0.000 description 56
- 230000015572 biosynthetic process Effects 0.000 description 52
- 238000004440 column chromatography Methods 0.000 description 52
- 239000002904 solvent Substances 0.000 description 51
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
- 238000003786 synthesis reaction Methods 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 47
- 239000011541 reaction mixture Substances 0.000 description 46
- 239000003921 oil Substances 0.000 description 43
- 235000019198 oils Nutrition 0.000 description 43
- 206010028980 Neoplasm Diseases 0.000 description 41
- 238000001914 filtration Methods 0.000 description 35
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
- 230000002829 reductive effect Effects 0.000 description 33
- 238000010992 reflux Methods 0.000 description 31
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 238000002329 infrared spectrum Methods 0.000 description 30
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 29
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 29
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 239000000706 filtrate Substances 0.000 description 26
- 238000012360 testing method Methods 0.000 description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 238000003756 stirring Methods 0.000 description 23
- 239000002244 precipitate Substances 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000011734 sodium Substances 0.000 description 21
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 18
- 201000011510 cancer Diseases 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 18
- 229910002651 NO3 Inorganic materials 0.000 description 17
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 17
- 238000000746 purification Methods 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 15
- 239000012043 crude product Substances 0.000 description 15
- 239000012230 colorless oil Substances 0.000 description 14
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- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (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)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12516699P | 1999-03-19 | 1999-03-19 | |
| US60125166 | 1999-03-19 | ||
| PCT/CA2000/000294 WO2000056743A1 (en) | 1999-03-19 | 2000-03-17 | Pharmaceutical compositions comprising metal complexes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU3268500A true AU3268500A (en) | 2000-10-09 |
Family
ID=22418482
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU32685/00A Abandoned AU3268500A (en) | 1999-03-19 | 2000-03-17 | Pharmaceutical compositions comprising metal complexes |
Country Status (15)
| Country | Link |
|---|---|
| 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) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ303156B6 (cs) | 1999-04-13 | 2012-05-09 | Anormed Inc. | Komplex cisplatiny a zpusob jeho prípravy |
| 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 |
| EP2319518A1 (en) | 2002-02-04 | 2011-05-11 | ALFAMA-Investigacao e Desenvolvimento de Produtos Farmaceuticos Lda. | Use of CO-releasing compounds for the manufacture of a medicament for the treatment of inflammatory diseases |
| 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 |
| GB2395432B (en) * | 2002-11-20 | 2005-09-14 | Northwick Park Inst For Medica | Therapeutic delivery of carbon monoxide to extracorporeal and isolated organs |
| ES2390457T3 (es) * | 2003-08-04 | 2012-11-13 | Johnson & Johnson Consumer Companies, Inc. | Métodos para el tratamiento de enfermedades dermatológicas |
| EP1712547B1 (en) | 2004-02-05 | 2011-12-14 | Kyorin Pharmaceutical Co., Ltd. | Bicycloester derivative |
| FR2873037B1 (fr) * | 2004-07-13 | 2008-04-11 | Univ Pasteur | Methodes et compositions pour le traitement de cancers |
| WO2007072018A2 (en) * | 2005-12-21 | 2007-06-28 | Oxford Biosensors Ltd | Redox mediators |
| GB0601394D0 (en) | 2006-01-24 | 2006-03-01 | Hemocorm Ltd | Therapeutic delivery of carbon monoxide |
| CA2645154C (en) | 2006-03-08 | 2011-11-29 | Kyorin Pharmaceutical Co., Ltd. | Method for producing aminoacetylpyrrolidinecarbonitrile derivative and production intermediate thereof |
| EP2032701B1 (en) * | 2006-06-23 | 2013-11-27 | Alethia Biotherapeutics Inc. | Polynucleotides and polypeptides involved in cancer |
| WO2008038305A2 (en) * | 2006-09-26 | 2008-04-03 | Jegannathan Srinivas | Therapeutical formulation comprising a thiazolidinedione and a nitric oxide scavenger. |
| JPWO2008114857A1 (ja) | 2007-03-22 | 2010-07-08 | 杏林製薬株式会社 | 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 |
| NZ592432A (en) | 2008-11-03 | 2013-01-25 | Alethia Biotherapeutics Inc | Antibodies that specifically block the biological activity of a tumor antigen Kidney associated antigen 1 (KAAG1) |
| 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 |
| PT3173427T (pt) | 2011-03-31 | 2019-09-17 | Adc Therapeutics Sa | Anticorpos contra antigénio associado ao rim 1 e fragmentos de ligação a antigénio dos mesmos |
| JP5978291B2 (ja) | 2011-04-19 | 2016-08-24 | アルファーマ インコーポレイテッドＡｌｆａｍａ，Ｉｎｃ． | 一酸化炭素放出分子およびその使用 |
| JP6134710B2 (ja) | 2011-07-21 | 2017-05-24 | アルファーマ インコーポレイテッドＡｌｆａｍａ，Ｉｎｃ． | 一酸化ルテニウム放出分子およびその使用 |
| PT2802351T (pt) | 2012-01-09 | 2019-06-27 | Adc Therapeutics Sa | Agentes para o tratamento de cancro da mama triplo negativo |
| 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 |
| EP3212610B1 (en) * | 2014-10-30 | 2020-10-28 | 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 |
|---|---|---|---|---|
| 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 |
| 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 |
| 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 WO PCT/CA2000/000294 patent/WO2000056743A1/en not_active Ceased
- 2000-03-17 EP EP00910468A patent/EP1163247A1/en not_active Withdrawn
- 2000-03-17 HU HU0400457A patent/HUP0400457A2/hu unknown
- 2000-03-17 KR KR1020017011819A patent/KR20010112343A/ko not_active Withdrawn
- 2000-03-17 PL PL00356683A patent/PL356683A1/xx not_active Application Discontinuation
- 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 IL IL14529000A patent/IL145290A0/xx unknown
- 2000-03-17 AU AU32685/00A patent/AU3268500A/en not_active Abandoned
- 2000-03-17 CA CA002367282A patent/CA2367282A1/en not_active Abandoned
- 2000-03-17 MX MXPA01009410A patent/MXPA01009410A/es unknown
- 2000-03-17 JP JP2000606604A patent/JP2004500321A/ja not_active Withdrawn
- 2000-03-17 CZ CZ20013307A patent/CZ20013307A3/cs unknown
- 2000-03-17 CN CN00806748A patent/CN1391577A/zh active Pending
-
2001
- 2001-09-18 NO NO20014526A patent/NO20014526L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO20014526D0 (no) | 2001-09-18 |
| MXPA01009410A (es) | 2003-06-06 |
| IL145290A0 (en) | 2002-06-30 |
| BR0011678A (pt) | 2002-02-26 |
| KR20010112343A (ko) | 2001-12-20 |
| NO20014526L (no) | 2001-10-16 |
| CZ20013307A3 (cs) | 2002-05-15 |
| CN1391577A (zh) | 2003-01-15 |
| WO2000056743A1 (en) | 2000-09-28 |
| CA2367282A1 (en) | 2000-09-28 |
| HUP0400457A2 (hu) | 2004-05-28 |
| US20020049190A1 (en) | 2002-04-25 |
| PL356683A1 (en) | 2004-06-28 |
| EP1163247A1 (en) | 2001-12-19 |
| JP2004500321A (ja) | 2004-01-08 |
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Legal Events
| Date | Code | Title | Description |
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| MK6 | Application lapsed section 142(2)(f)/reg. 8.3(3) - pct applic. not entering national phase | ||
| TH | Corrigenda |
Free format text: IN VOL 15, NO 2, PAGE(S) 350-353 UNDER THE HEADING APPLICATIONS LAPSED, REFUSED OR WITHDRAWN PLEASE DELETE ALL REFERENCE TO APPLICATION NO. 32685/00 |