GB2134103A - Novel organic platinum complex and process for the preparation thereof - Google Patents
Novel organic platinum complex and process for the preparation thereof Download PDFInfo
- Publication number
- GB2134103A GB2134103A GB08301602A GB8301602A GB2134103A GB 2134103 A GB2134103 A GB 2134103A GB 08301602 A GB08301602 A GB 08301602A GB 8301602 A GB8301602 A GB 8301602A GB 2134103 A GB2134103 A GB 2134103A
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- United Kingdom
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- formula
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- compound
- platinum complex
- organic platinum
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 title claims abstract description 59
- 229910052697 platinum Inorganic materials 0.000 title claims abstract description 27
- 238000000034 method Methods 0.000 title abstract description 20
- 238000002360 preparation method Methods 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 50
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract 2
- 239000001257 hydrogen Substances 0.000 claims abstract 2
- WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 claims description 16
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 claims description 14
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 14
- 229910002651 NO3 Inorganic materials 0.000 claims description 9
- 229910052783 alkali metal Inorganic materials 0.000 claims description 8
- 150000001340 alkali metals Chemical class 0.000 claims description 8
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- YPNVIBVEFVRZPJ-UHFFFAOYSA-L silver sulfate Chemical compound [Ag+].[Ag+].[O-]S([O-])(=O)=O YPNVIBVEFVRZPJ-UHFFFAOYSA-L 0.000 claims description 6
- 229910000367 silver sulfate Inorganic materials 0.000 claims description 6
- 229910001513 alkali metal bromide Inorganic materials 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 229910001516 alkali metal iodide Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- 150000003057 platinum Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 abstract description 6
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 238000004458 analytical method Methods 0.000 description 11
- 239000000843 powder Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- OOTKJPZEEVPWCR-UHFFFAOYSA-N n-methyl-1-pyridin-2-ylmethanamine Chemical compound CNCC1=CC=CC=N1 OOTKJPZEEVPWCR-UHFFFAOYSA-N 0.000 description 7
- 238000001914 filtration Methods 0.000 description 6
- 238000002329 infrared spectrum Methods 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 229910021607 Silver chloride Inorganic materials 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 5
- -1 1,2-dihydroxyethyl Chemical group 0.000 description 4
- 206010003445 Ascites Diseases 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000000719 anti-leukaemic effect Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- ROBFUDYVXSDBQM-UHFFFAOYSA-N hydroxymalonic acid Chemical compound OC(=O)C(O)C(O)=O ROBFUDYVXSDBQM-UHFFFAOYSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 1
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- XPQIPUZPSLAZDV-UHFFFAOYSA-N 2-pyridylethylamine Chemical compound NCCC1=CC=CC=N1 XPQIPUZPSLAZDV-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000007093 Leukemia L1210 Diseases 0.000 description 1
- 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 244000061661 Orchis Species 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 208000006268 Sarcoma 180 Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 208000009916 Yoshida Sarcoma Diseases 0.000 description 1
- 150000007854 aminals Chemical class 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical class [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 238000011474 orchiectomy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- SDDHFOZMAHSVOA-UHFFFAOYSA-N platinum;pyridin-2-ylmethanamine Chemical compound [Pt].NCC1=CC=CC=N1 SDDHFOZMAHSVOA-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 229940100890 silver compound Drugs 0.000 description 1
- 150000003379 silver compounds Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229940023144 sodium glycolate Drugs 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- ZNCPFRVNHGOPAG-UHFFFAOYSA-L sodium oxalate Chemical compound [Na+].[Na+].[O-]C(=O)C([O-])=O ZNCPFRVNHGOPAG-UHFFFAOYSA-L 0.000 description 1
- 229940039790 sodium oxalate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
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
- 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
- C07F15/0086—Platinum compounds
- C07F15/0093—Platinum compounds without a metal-carbon linkage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Abstract
A novel organic platinum complex of the formula: <IMAGE> wherein R<1> is hydrogen or methyl, Y<1> and Y<2> are the same or different and each is halogen, NO3 or R<2>-COO-, or y<1> and y<2> combine to form SO4, PO3OH or <IMAGE> R<2> is a hydroxy-substituted lower alkyl or acetyl, and m and n are each 0, 1 or 2 with the proviso of 0</=m+n</=2, and a process for the preparation thereof. The compound [I] has an excellent anti-tumor activity and is useful as an anti-tumor agent.
Description
SPECIFICATION
Novel organic platinum complex and process for the preparation thereof
The present invention relates to a novel organic platinum complex and a process for the preparation thereof. More particularly, it relates to a novel organic platinum complex of the formula:
wherein R1 is a hydrogen atom or methyl group, Y1 and Y2 are the same or different and each is a halogen atom, NO3 or a group of the formula: R2-COO-, or Y1 and Y2 combine to form a group of the formula:
-O-CO-(CHOH)m-(CH2)n-CO-O-,
R2 is a hydroxy-substituted lower alkyl or acetyl group, and m and n are each integers of O, 1 or 2 with the proviso of Om+n12, and a process for the preparation of the organic platinum complex.
The organic platinum complex [I] of the present invention has an excellent anti-tumor activity and is useful as an anti-tumor agent.
There have hitherto been prepared many organic platinum complexes wherein various diamines are used as a ligand, and the anti-tumor activity of these compounds has also been studied (cf.
Rosenberg et al, Nature, 222, 385 (1969), etc.). However, these known compounds have toxicity to kidney and the organ of hearing [cf. A. W. Prestayko, Cancer and Chemotherapy, 3, 133 (1981)].
As a result of extensive study by the present inventors, it has been found that a certain organic platinum complex containing 2-aminomethylpyridine or its derivative as a ligand has excellent antitumor activity without increasing the toxicity.
The organic platinum complex of the present invention is a compound of the formula [I] wherein, for example, R1 is a hydrogen atom or methyl group, Y1 and Y2 are the same or different and each is a halogen atom such as for example chlorine, bromine or iodine, NO3, or a group of the formula: HOCH2COO-,
CH3CH(OH)COO-,
HOCH2CH(OH)COO-,
HOCH2CH2COO-,
(CH3)2CHCH(OH)COO- or CH3COCOO-, or Y1 and Y2 combine to form a group of the formula:
-0-CO-C 0-0-, --COO-CH2CH2--COO--O- or -0-CO-CH(OH)CH(OH)-CO-O-.
Preferred compounds are a compound of the formula [I] wherein R1 is a hydrogen atom or methyl group, V1 andY2 are the same or different and each is a chlorine atom, NO3 or a group of the formula: HOCH2COO-, or yet and Y2 combine to form a group of the formula:
--O--CO--CO--O-- or -O-C0-CH2-C0#)-.
In the present specification, the term "a lower alkyl group" denotes an alkyl group having 1 to 4 carbon atoms.
The organic platinum complex [I] of the present invention can be prepared for example by the following processes.
[Process A]:
A compound of the formula: K2Pt(ll)X'4 or Na2Pt(ll)X'4 (wherein X' is a halogen atom) is reacted with a compound of the formula:
wherein R1 is as defined above to give an organic platinum complex of the formula:
wherein R1 and X' are as defined above.
[Process B]:
A compound of the formula:
wherein R1 is as defined above is reacted with silver sulfate or silver nitrate to give an organic platinum complex of the formula:
wherein Y3 and Y4 are the same each is NO3, or Y3 and Y4 combine to form a group of the formula:
and R1 is as defined above.
[Process Ci: A compound of the formula:
wherein R1 is as defined above is reacted with an alkali metal bromide, an alkali metal iodide, di(alkali metal) phosphate, or a compound of the formula: R2-COOM' (wherein R2 is as defined above and M' is an alkali metal) or
M'-O-CO-(CHOH)m-(CH2)n-CO-O-M' (wherein m, n and M' are as defined above) to give an organic platinum complex of the formula:
wherein Y5 and V6 are the same or different and each is bromine, iodine, NO3, or a group of the formula: RLCO0 (R2 is as defined above), or V5 and V6 combine to form a group of the formula
or
--O--CO--(CHOH)m (CH2)n--CO--O- (m and n are as defined above), and R1 is as defined above.
The procedure of the above processes is explained in detail below.
Process A: This process can be carried out by dissolving the compound of the formula: K2Pt(ll)X'4 or Na2Pt(ll)X'4 in an appropriate solvent and adding thereto a compound (II) and stirring the mixture.
Examples of the starting K2Pt(ll)X'4 and Na2Pt(ll)X'4 are K2Pt(ll)CI4 and Na2Pt(ll)CI4 (i.e. X' is chlorine).
Examples of other starting compounds (II) are a compound of the formula (II) wherein R1 is as defined above. The solvent is preferably water. The starting compound K2Pt(ll)X'4 or Na2Pt(ll)X'4 is preferably used in an amount uf about 0.8 to about 1 .t) "lole to the c,ompcuna (;), { ld the solvents is preferably used in an amount of about 5 to about 50 times as much as the amount of the starting K2Pt(ll)X'4 or
Na2Pt(ll)X'4. The reaction is usually carried out at room temperature.
Process B: This process is preferably carried by adding the compound (II) which is prepared by
Process A to an appropriate solvent, adding thereto silver sulfate or silver nitrate and stirring the mixture. The solvent is preferably water. Silver nitrate is preferably used in an amount of about 2 moles to 1 mole of the compound (III), and silver sulfate is preferably used in an approximately equimolar amount to the compound (III). The solvent is preferably used in an amount of about 20 to about 500 times as much as the amount of the compound (III). The reaction is usually carried out at a room temperature. The reaction of the compound (III) and silver salt is preferably carried out in the absence of light.
Process C: This process is preferably carried out by adding the compound (IV) which is prepared by Process B to an appropriate solvent, adding thereto an alkali metal bromide, an alkali metal iodide, di(alkali metal) phosphate or a compound of the formula: R2--COOM' (R2 and M' are as defined above) or M'-O-CO-(CHOH),-(CH,),-CO-O-M" (M', m and n are as defined above), and stirring the mixture. Examples of the alkali metal bromide are sodium bromide and potassium bromide, and of the alkali metal iodide are sodium iodide and potassium iodide. Examples of the di(alkali metal) phosphate are Na2HPO4 and K2HPO4.Examples of the compounds of the formula R2--COOM' are compounds wherein R2 is a hydroxy-substituted lower alkyl group such as for example the hydroxymethyl, 1-hydroxyethyl, 1,2-dihydroxyethyl, 2-hydroxyethyl and 1 -hydroxy-2-methylpropyl groups or an acetyl group, and M' is an alkali metal such as for example sodium or potassium. Examples of the compounds of the formula M'-O-CO-(CHOH),-(CH,),-CO-O-M' are the disodium or dipotassium salt of oxalic acid, malonic acid, hydroxymalonic acid, d,1-malic acid, d,1 -tartaric acid or succinic acid. The solvent is preferably water.The alkali metal bromide, alkali metal iodine and the compound of the formula R2--COOM' are preferably used in an amount of about 1 or 2 moles to 1 mole of the compound (IV), and di(alkali metal) phosphate and the compound of the formula M'-O-CO-CHOH),-(CH,),-CO-O-M' are preferably used in an approximately equimolar amount to the compound (IV). The solvent is preferably used in an amount of about 10 to about 200 times as much as the amount of the compound (IV). The reaction is usually carried out at room temperature. The dissolution of the compound (IV) in a solvent is preferably done with heating.
The desired compound [IJ prepared by the above processes can be isolated from the reaction mixture, by, for example, a conventional method, e.g. by filtering the resulting precipitate. If required, prior to said filtration the reaction mixture may be concentrated or it may be subjected to a column chromatography, followed by concentration. When silver chloride is produced as a by-product in the above reactions, it is preferable to separate off the silver chloride by filtration, to add in portions a 5% aqueous potassium chloride solution to the filtrate and filter in order to remove the unreacted silver compound in the form of silver chloride, and then to subject the resulting filtrate to the above isolation procedure.
The organic platinum complex [I] thus obtained shows potent anti-tumor activity against various tumor cells such as, for example, Ehrlich carcinoma, sarcoma 180, leukemia L-1 210, Lewis lung carcinoma, Yoshida sarcoma and rat ascites hepatoma. It may be useful to prolong the survival time of warm-blood aminals, including human, afflicted with tumors and/or minimize the growth of tumors in said animals.For example, according to experiments on anti-leukemia L-1 21 0 activity (wherein the test compound was intraperitoneally administered for 5 days to mice grafted intraperitoneally with leukemia L-1 210 cells) and experiments on activity against Ehrlich ascites carcinoma, cis-oxalate(2aminomethylpyridine) platinum (II) shows an increase of more than 745% in life span (i.e. the ratio of the average survival days in the treated animals and in the control animals) in anti-leukemia L-1210 activity in a dose of 50 mg/kg/day, and 100% inhibition of Ehrlich ascites carcinoma (i.e. the ratio of the amount of ascites carcinoma in the treated animals and in the control animals) in a dose of 3 to 50 mg/kg/day.The compounds of the present invention are also useful for the treatment of various other tumors such as, for example, prostate tumor, orchis tumor, ovary tumor, malignant lymphoma, leukemia and breast cancer. The compound [I] of the present invention shows potent anti-tumor activities and has a low toxicity, and hence, can be used as an anti-tumor agent with a high safety index.
The organic platinum complex [I] of the present invention can be used for pharmaceutical use in the form of a pharmaceutical preparation suitable for either oral or parenteral administration, preferably for parenteral administration. The compound [I] may also be used in conjunction or admixture with a pharmaceutical excipient. The excipient selected should be one which does not react with the compound [I]. Examples of suitable excipients are gelatin, lactose, glucose, sodium chloride, starch, magnesium stearate and talcum. Other known medicinal excipients may be employed. The pharmaceutical preparation may be solid dosage from such as for example, a tablet, a coated tablet, a pill or a capsule; or a liquid dosage form such as for example, a solution, a suspension or an emulsion.
Further, the compound [I] may be used together with an isotonic agent such as for example, mannitol, sodium chloride, glucose, sorbitol, glycerol, xylitol, fructose, mannose, or the like. The pharmaceutical preparation may be sterilized and/or may contain auxiliaries such as for example preserving and stabilizing agents. The dose of the compound [I] for pharmaceutical use depends on route of administration; the age, weight and condition of the host; and the particular disease to be treated. In general, it may be used for pharmaceutical use at a dose of about 20 to about 1000 mg/m2, especially 50 to 500 mg/m2, per day.
A dosage of 50 mg/m2 is roughly equal to 1.5 mg/kg which in turn is roughly equal to 75 mg/patient weighing 50 kg.
Practical and presently-preferred embodiments of the present invention are illustratively shown in the following Examples.
Example 1
2-Aminoethylpyridine (1.20 g) is added to a solution of potassium tetrachloroplatinate (11) (4.15 g) in water (50 ml), and the mixture is stirred at room temperature overnight. The precipitated crystal is separated by filtration, washed with a small amount of cold water and dried to give cis-dichloro(2aminomethylpyridine) platinum (11) (3.19 g) as brownish yellow crystals.
Elementary analysis for C6H8N2Cl2Pt: Found (%): C, 19.26; H, 2.15; N, 7.48
Calcd. (%): C, 19.41; H, 2.22; N, 7.44 IRPNuaiol (cm t): 3240, 3200, 3110, 1635.
The IR spectrum of the above compound is shown in the accompanying Figure 1.
Example 2
A solution of silver nitrate (3.40 g) in water (40 ml) is added to a suspension of cis-dichloro(2aminomethylpyridine) platinum (11) (3.74 g) prepared as in Example 1 in water (200 mg), and the mixture is stirred in the absence of light at room temperature over two nights. The precipitated silver chloride is filtered off, and a 5% aqueous potassium chloride solution is added in portions to the filtrate to convert the unreacted silver nitrate into silver chloride which is removed by filtration. The resulting filtrate is concentrated to dryness under reduced pressure and then dried to give cis-dinitrato(2-aminomethylpyridine) platinum (11) (3.9 g) as a pale yellow powder.
Elementary analysis for C6H8N4O6Pt: Found(%): C, 16.86, H, 1.87; N, 13.11 Calcd. (%): C, 16.95; H, 1.76; N, 12.96 IRvNUaiXl (cm-l): 3280, 3220, 3150, 1620, 1510, 1280.
The IR spectrum of the above compound is shown in accompanying Figure 2.
Example 3
Cis-dinitrato(2-aminomethylpyridine) platinum (Il) (0.43 g) prepared as in Example 2 is dissolved in water (40 ml) with heating, potassium bromide (0.71 g) is added and the mixture is stirred at room temperature overnight. The precipitated crystals are separated by filtration and dried to give cisbromo(2-aminomethylpyridine) platinum (11) (0.43 g) as a brownish yellow powder.
Elementary analysis for C6H8H2Br2Pt: Found (%): C, 15.55; H, 1.73; N, 6.05 Calcd. (%): C, 1 5.73; H, 1.68; N, 6.28 IR#max Nu jol (cm-): 3220,3180,3100, 1615.
The IR spectrum of the above compound is shown in the accompanying Figure 3.
Example 4
Cis-dichloro(2-aminomethylpyridine) platinum (II) (0.37 g) prepared as in Example 1 is added to a solution of silver sulfate (0.31 g) in water (100 ml), and the mixture is stirred in the absence of light at room temperature over two nights. The reaction mixture is treated in the same manner as described in
Example 2 to give cis-sulfato(2-aminomethylpyridine) platinum (II) (0.32 g) as a pale yellowish white powder.
Elementary analysis for C6H8N204SPt:
Found (%): C, 18.04; H, 2.00; N, 7.01 Calcd. (%): C, 17.88; H, 1.93; N, 6.85 I RVNmUaJxOI (cm-): 3250, 3210, 1610, 1120, 1030.
Example 5
Cis-dinitrato(2-aminomethylpyridine) platinum (II) (0.43 g) prepared as in Example 2 is dissolved in water (40 ml) with heating, sodium glycolate (0.20 g) is added, and the mixture is allowed to stand at room temperature for 7 days. The reaction mixture is concentrated under reduced pressure to give cis-diglycolato(2-aminomethylpyridine) platinum (II) (0.35 g) as a white powder.
Elementary analysis for C10H14N206Pt:
Found (%): C, 26.49; H, 3.09; N, 6.18 Calcd. (%): C, 26.35; H, 3.26; N, 6.01 I RpmNUaJxO (cm-): 3240, 3130, 1640, 1620.
The IR spectrum of the above compound is shown in the accompanying Figure 4.
Examples 6 to 9
In the same manner as described in Example 5, the following compounds are prepared by using cis-dinitrato(2-aminomethylpyridine) platinum (II) and the sodium salt of an organic carboxylic acid.
(6) Cis-dipyruvinato(2-aminomethylpyridine) platinum (II), pale yellow powder, yield: 75%.
Elementary analysis for C12H14N2O6Pt: Found (%): C, 30.18; H, 2.93; N, 5.87 Calcd. (%): C, 30.14; H, 2.78; N, 5.69 IR#max Nujol(cm-): 3300, 3210, 1760, 1640.
(7) Cis-oxalato(2-aminomethylpyridine) platinum (II), colourless crystalline powder, yield: 90%.
Elementary analysis for C6H8N2O4Pt: Found (%): C, 24.55; H, 2.04; N,7.16
Calcd. (%): C, 24.72; H, 2.31; N, 6.98 IR#max Nujol (cm-) 3220, 3130, 1720, 1660, 1610.
The IR spectrum of the above compound is shown in the accompanying Figure 5.
(8) Cis-malonato(2-aminomethylpyridine) platinum (II), white powder, yield: 82%.
Elementary analysis for CgH10N204Pt Found (%): C, 26.66; H, 2.46; N, 6.91 Calcd. (%): C, 26.78; H, 2.28; N, 7.12 lRt;NmLOI (cm-): 3220,3140,1640.
(9) Cis(glycolato) (nitrato) (2-aminomethylpyridine) platinum (II), pale yellow powder, yield: 70%.
Elementary anslysis for C8H,1N306Pt: Found (%): C,21.81; H, 2.50; N, 9.54 Calcd. (%): C,21.73; H, 2.33; N, 9.71 IR#max Nujol (cm-): 3210, 3120, 1600.
Example 10
(1) A mixture of pyridine-2-aldehyde (5.4 g), methylamine hydrochloride (0.5 g) and methanolic methylamine (3 g in 100 ml) is hydrogenated in the presence of Pd/C catalyst to give 2 (methylaminomethyl)pyridine (4.5 g), b.p. 79-81 C/14 mmHg.
IRVNmUaJxOI (cm-): 3340, 1 590, 1 570 Mass m/e: 121 (M±1), 92 (M±30 (NHCH3))
NMR (CDCl3) b: 2.47 (3H, s, NCH3), 2.20 (1 H, s, NH), 3.87 (2H, s, CH2), 7.05-7.80 (3H, m,
proton at pyridine ring), 8.56 (1 H, d, J=3.7 Hz, proton at pyridine ring).
(2) In the same manner as described in Example 1, potassium platinate chloride (4.15 g) is reacted with 2-(methylaminomethyl)pyridine (1.34 g) to give cis-dichloro(2-methylaminomethyl)pyridine) platinum (II) (3.3 g) as pale yellow crystals.
Elementary analysis for C7H,ON2ClsPt: Found (%): C, 21.65; H, 2.59; N, 7.21 Calcd. (%): C, 21.59; H, 2.59; N, 7.19 lRVNmUaJxOI (cm-): 3160, 1620.
The IR spectrum of the above compound is shown in the accompanying Figure 6.
Example 11
In the same manner as described in Example 2, cis-dichloro(2-(methylaminomethyl)pyridine) platinum (11) (0.39 g) prepared as in Example 10 is reacted with silver nitrate (0.34 g) to give cisdinitrato(2-(methylaminomethyl)pyridine) platinum (II) (0.40 g) as a pale yellow powder.
Elementary analysis for C7H10N406Pt:
Found (%): C, 19.04; H, 2.26; N, 12.69 Calcd. (%): C, 19.26; H, 2.41; N, 12.81 IRVNmUaŎI (cm-): 3190, 1620, 1 520, 1280.
Example 12
In the same manner as described in Example 5, cis-dinitrato(2-(methylaminomethyl)pyridine) platinum (II) (0.44 g) prepared as in Example 11 is reacted with sodium oxalate (0.13 g) to give cisoxalato(2-(methylaminomethyl)pyridine) platinum (II) (0.37 g) as a white powder.
Elementary analysis for C > H10N204Pt Found (%): C, 26.66; H, 2.46; N, 6.91 Calcd. (%): C, 26.52; H, 2.61; N, 6.78 IR#maxNujol (cm-1): 3160, 1720, 1650.
Claims (10)
1. An organic platinum complex of the formula:
wherein R' is a hydrogen atom or methyl group, Y' and V2 are the same or different and each is a halogen atom, NO3 or a group of the formula: R2-C00-, or Y1 and V2 combine to form a group of the formula:
-O-CO-(CHOH)m-(CH2)n-CO-O-,
R2 is a hydroxy-substituted lower alky or acetyl group, and m and n are each integers of 0, 1 or 2 with the proviso of O~m+n < 2.
2. Complex according to claim 1, wherein Y' and V2 are the same or different and each is a chlorine atom, NO3 or a group of the formula: HOCH2COO- or Y' and V2 combine to form a group of the formula:
-O-CO-CO-O- or
-O-CO-CH2-CO-O-.
3. Complex according to claim 1 which is cis-oxalato(2-aminomethylpyridine) platinum (II).
4. Organic platinum complexes of formula (i) substantially as herein described with reference to and as illustrated in any of the Examples.
5. A process for preparing an organic platinum complex of the formula:
wherein R' is e hydrogen ntom or methyl group, snd X' is a halogen atom, which cbmpr:sss reacting a compound of the formula: K2Pt(ll)X'4 or Na2Pt(ll)X'4 with a compound of the formula:
6. A process for preparing an organic platinum complex of the formula:
wherein R' is a hydrogen atom or methyl group, and Y3 and Y4 are the same and each is NO3, or Y3 and Y4 combine to form a group of the formula:
which comprises reacting a compound of the formula:
with silver sulfate or silver nitrate.
7. A process for preparing an organic platinum complex of the formula:
wherein R' is a hydrogen atom or methyl group, Y5 and V6 are the same or different and each is bromine, iodine, NO3, or a group of the formula: R2-C0O-, or V5 and V6 combine to form a group of the formula:
-O-CO-(CHOH)m-(CH2)n-CO-O-,
R2 is a hydroxy-substituted lower alkyl group or acetyl group, and m and n are each integers of 0, 1 or 2 with the proviso of O~m+n~2, which comprises reacting a compound of the formula:
with an alkali metal bromide, an alkali metal iodide, silver sulfate, or a compound of the formula: R2--COOM' (M' is an alkali metal) or
M'-O-CO-(CHOH)m-(CH2)n-CO-O-M'.
8. A process for preparing an organic platinum complex of formula (I) substantially as herein described with reference to and as illustrated in any of the Examples.
9. A pharmaceutical composition, which comprises as an essential active ingredient an organic platinum complex as claimed in any of claims 1 to 4 in admixture with a pharmaceutically acceptable carrier or diluent.
10. A pharmaceutical composition according to claim 9 for use as an anti-tumor agent.
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB08301602A GB2134103A (en) | 1983-01-21 | 1983-01-21 | Novel organic platinum complex and process for the preparation thereof |
| KR1019840000130A KR840007599A (en) | 1983-01-21 | 1984-01-13 | Method for producing platinum complex organics |
| JP59008346A JPS59139360A (en) | 1983-01-21 | 1984-01-19 | Novel organo-platinum complex and its preparation |
| ES529060A ES529060A0 (en) | 1983-01-21 | 1984-01-20 | AN ORGANIC PLATINUM COMPLEX |
| EP84300379A EP0115929A1 (en) | 1983-01-21 | 1984-01-23 | Novel organic platinum complex and process for the preparation thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB08301602A GB2134103A (en) | 1983-01-21 | 1983-01-21 | Novel organic platinum complex and process for the preparation thereof |
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| GB8301602D0 GB8301602D0 (en) | 1983-02-23 |
| GB2134103A true GB2134103A (en) | 1984-08-08 |
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|---|---|---|---|
| GB08301602A Withdrawn GB2134103A (en) | 1983-01-21 | 1983-01-21 | Novel organic platinum complex and process for the preparation thereof |
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| JP (1) | JPS59139360A (en) |
| GB (1) | GB2134103A (en) |
Cited By (1)
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|---|---|---|---|---|
| WO2009077462A2 (en) * | 2007-12-14 | 2009-06-25 | Rheinisch-Westfälische Technische Hochschule Aachen | Chiral cycloplatinized complexes, method for the production thereof and their use in medicine and catalysts |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62244965A (en) * | 1986-04-18 | 1987-10-26 | 三井建設株式会社 | Concrete bucket apparatus |
| ES2016441A6 (en) * | 1988-04-07 | 1990-11-01 | Chugai Pharmaceutical Co Ltd | A process for producing 1,1-cyclobutane dicarboxylate (2- aminomethylpyrrolidine) platinum II and its optically active derivatives |
| WO2005051966A1 (en) * | 2003-11-25 | 2005-06-09 | Platco Technologies (Proprietary) Limited | Platinum(ii) complexes, preparation and use |
| JP5960321B1 (en) * | 2015-05-12 | 2016-08-02 | 田中貴金属工業株式会社 | Chemical vapor deposition material comprising an organic platinum compound and chemical vapor deposition method using the chemical vapor deposition material |
-
1983
- 1983-01-21 GB GB08301602A patent/GB2134103A/en not_active Withdrawn
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1984
- 1984-01-19 JP JP59008346A patent/JPS59139360A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009077462A2 (en) * | 2007-12-14 | 2009-06-25 | Rheinisch-Westfälische Technische Hochschule Aachen | Chiral cycloplatinized complexes, method for the production thereof and their use in medicine and catalysts |
| WO2009077462A3 (en) * | 2007-12-14 | 2009-09-17 | Rheinisch-Westfälische Technische Hochschule Aachen | Chiral cycloplatinized complexes, method for the production thereof and their use in medicine and catalysts |
| US8394979B2 (en) | 2007-12-14 | 2013-03-12 | Rheinische-Westfalische Technische Hochschule Aachen | Process for preparing cycloplatinated platinum complexes, platinum complexes prepared by this process and the use thereof |
| CN101939326B (en) * | 2007-12-14 | 2013-06-05 | 亚琛工业大学 | Method for producing cycloplatinized platinum complexes, platinum complexes produced by said method, and the use thereof |
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| Publication number | Publication date |
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| GB8301602D0 (en) | 1983-02-23 |
| JPS59139360A (en) | 1984-08-10 |
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