JP5015451B2 - ホスフィン遷移金属錯体、その製造方法およびそれを含有する抗癌剤 - Google Patents
ホスフィン遷移金属錯体、その製造方法およびそれを含有する抗癌剤 Download PDFInfo
- Publication number
- JP5015451B2 JP5015451B2 JP2005352476A JP2005352476A JP5015451B2 JP 5015451 B2 JP5015451 B2 JP 5015451B2 JP 2005352476 A JP2005352476 A JP 2005352476A JP 2005352476 A JP2005352476 A JP 2005352476A JP 5015451 B2 JP5015451 B2 JP 5015451B2
- Authority
- JP
- Japan
- Prior art keywords
- bis
- group
- gold
- ethane
- phosphino
- 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.)
- Expired - Fee Related
Links
- -1 Phosphine transition metal Chemical class 0.000 title claims description 83
- 229910052723 transition metal Inorganic materials 0.000 title claims description 42
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 title claims description 34
- 229910000073 phosphorus hydride Inorganic materials 0.000 title claims description 34
- 239000002246 antineoplastic agent Substances 0.000 title claims description 19
- 238000000034 method Methods 0.000 title description 15
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical group [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 15
- 229910052737 gold Inorganic materials 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 239000013543 active substance Substances 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000000129 anionic group Chemical group 0.000 claims description 8
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 8
- 239000010931 gold Substances 0.000 claims description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 5
- 239000002184 metal Substances 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- TYGBCXMBJCGZGI-UHFFFAOYSA-M tert-butyl-[2-[tert-butyl(pyridin-2-yl)phosphanyl]ethyl]-pyridin-2-ylphosphane;chlorogold Chemical compound [Au]Cl.C=1C=CC=NC=1P(C(C)(C)C)CCP(C(C)(C)C)C1=CC=CC=N1.C=1C=CC=NC=1P(C(C)(C)C)CCP(C(C)(C)C)C1=CC=CC=N1 TYGBCXMBJCGZGI-UHFFFAOYSA-M 0.000 claims description 5
- QTQKJQQEUAJLDJ-UHFFFAOYSA-M [I-].[Au+].CC(C)(C)P(CCP(c1ccccn1)C(C)(C)C)c1ccccn1.CC(C)(C)P(CCP(c1ccccn1)C(C)(C)C)c1ccccn1 Chemical compound [I-].[Au+].CC(C)(C)P(CCP(c1ccccn1)C(C)(C)C)c1ccccn1.CC(C)(C)P(CCP(c1ccccn1)C(C)(C)C)c1ccccn1 QTQKJQQEUAJLDJ-UHFFFAOYSA-M 0.000 claims description 3
- QSZBIBGHGBUYPR-UHFFFAOYSA-M tert-butyl-[2-[tert-butyl(pyridin-2-yl)phosphanyl]ethyl]-pyridin-2-ylphosphane gold(1+) bromide Chemical compound [Br-].[Au+].CC(C)(C)P(CCP(c1ccccn1)C(C)(C)C)c1ccccn1.CC(C)(C)P(CCP(c1ccccn1)C(C)(C)C)c1ccccn1 QSZBIBGHGBUYPR-UHFFFAOYSA-M 0.000 claims description 3
- MCQIBFLLOUDXLV-UHFFFAOYSA-M tert-butyl-[2-[tert-butyl(pyrimidin-2-yl)phosphanyl]ethyl]-pyrimidin-2-ylphosphane gold(1+) bromide Chemical compound [Br-].[Au+].CC(C)(C)P(CCP(c1ncccn1)C(C)(C)C)c1ncccn1.CC(C)(C)P(CCP(c1ncccn1)C(C)(C)C)c1ncccn1 MCQIBFLLOUDXLV-UHFFFAOYSA-M 0.000 claims description 3
- IQBADBKSOXMGLA-UHFFFAOYSA-M tert-butyl-[2-[tert-butyl(pyrimidin-2-yl)phosphanyl]ethyl]-pyrimidin-2-ylphosphane gold(1+) chloride Chemical compound [Cl-].[Au+].CC(C)(C)P(CCP(c1ncccn1)C(C)(C)C)c1ncccn1.CC(C)(C)P(CCP(c1ncccn1)C(C)(C)C)c1ncccn1 IQBADBKSOXMGLA-UHFFFAOYSA-M 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 2
- ATGIETUGWDAYPU-UHFFFAOYSA-M gold monoiodide Chemical compound [Au]I ATGIETUGWDAYPU-UHFFFAOYSA-M 0.000 claims 1
- DQIIMJSUIJYGSI-UHFFFAOYSA-N tert-butyl-[2-[tert-butyl(pyrimidin-2-yl)phosphanyl]ethyl]-pyrimidin-2-ylphosphane Chemical compound N=1C=CC=NC=1P(C(C)(C)C)CCP(C(C)(C)C)C1=NC=CC=N1 DQIIMJSUIJYGSI-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 51
- 238000006243 chemical reaction Methods 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 230000001093 anti-cancer Effects 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 11
- 229960004316 cisplatin Drugs 0.000 description 11
- FDWREHZXQUYJFJ-UHFFFAOYSA-M gold monochloride Chemical compound [Cl-].[Au+] FDWREHZXQUYJFJ-UHFFFAOYSA-M 0.000 description 11
- 206010028980 Neoplasm Diseases 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- BWJRMVLPCQPWGR-UHFFFAOYSA-N boron;phosphane Chemical group [B].P BWJRMVLPCQPWGR-UHFFFAOYSA-N 0.000 description 8
- 201000011510 cancer Diseases 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- 229910001873 dinitrogen Inorganic materials 0.000 description 7
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 229910003771 Gold(I) chloride Inorganic materials 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 125000002947 alkylene group Chemical group 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical group [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 229910052709 silver Inorganic materials 0.000 description 6
- 239000004332 silver Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 229920002261 Corn starch Polymers 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 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 5
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- CFFBBJBFIIKTCH-UHFFFAOYSA-N borane methylphosphane Chemical compound B.CP CFFBBJBFIIKTCH-UHFFFAOYSA-N 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 229910052802 copper Inorganic materials 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- XGELIJUZAOYNCA-UHFFFAOYSA-N gold;phosphane Chemical compound P.[Au] XGELIJUZAOYNCA-UHFFFAOYSA-N 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000006210 lotion Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 description 3
- 206010062129 Tongue neoplasm Diseases 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 206010017758 gastric cancer Diseases 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 3
- OAHWAYLLZSUVNQ-UHFFFAOYSA-N phenyl-[2-[phenyl(pyridin-2-yl)phosphanyl]ethyl]-pyridin-2-ylphosphane Chemical compound C=1C=CC=CC=1P(C=1N=CC=CC=1)CCP(C=1N=CC=CC=1)C1=CC=CC=C1 OAHWAYLLZSUVNQ-UHFFFAOYSA-N 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 201000011549 stomach cancer Diseases 0.000 description 3
- OCNLYKUQSPOEEP-UHFFFAOYSA-N tert-butyl-[2-[tert-butyl(pyridin-2-yl)phosphanyl]ethyl]-pyridin-2-ylphosphane Chemical compound C=1C=CC=NC=1P(C(C)(C)C)CCP(C(C)(C)C)C1=CC=CC=N1 OCNLYKUQSPOEEP-UHFFFAOYSA-N 0.000 description 3
- 201000006134 tongue cancer Diseases 0.000 description 3
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 2
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- COCBFFPCZXEFHW-UHFFFAOYSA-N B.CP(c1ccccc1)c1ccccn1 Chemical compound B.CP(c1ccccc1)c1ccccn1 COCBFFPCZXEFHW-UHFFFAOYSA-N 0.000 description 2
- PKPBCVSCCPTDIU-UHFFFAOYSA-N B.P Chemical group B.P PKPBCVSCCPTDIU-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- CEWSRLQSAVUNRB-UHFFFAOYSA-N CCP(C1=CC=CC=N1)C(C)(C)C Chemical compound CCP(C1=CC=CC=N1)C(C)(C)C CEWSRLQSAVUNRB-UHFFFAOYSA-N 0.000 description 2
- OXXISVYNHWZRKR-UHFFFAOYSA-N CCP(C1=NC=CC=N1)C(C)(C)C Chemical compound CCP(C1=NC=CC=N1)C(C)(C)C OXXISVYNHWZRKR-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 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 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 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
- 229920000084 Gum arabic Polymers 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 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 2
- 231100000111 LD50 Toxicity 0.000 description 2
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 239000007923 nasal drop Substances 0.000 description 2
- 229940100662 nasal drops Drugs 0.000 description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 description 2
- 125000004437 phosphorous atom Chemical group 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- XOJVVFBFDXDTEG-UHFFFAOYSA-N pristane Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 201000000849 skin cancer Diseases 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- NEMYGKLAKGMLPU-UHFFFAOYSA-N 2-(2,5-diphenyl-1,3-dihydrotetrazol-1-ium-1-yl)-4,5-dimethyl-1,3-thiazole;bromide Chemical compound [Br-].S1C(C)=C(C)N=C1N1C(C=2C=CC=CC=2)=NN[NH+]1C1=CC=CC=C1 NEMYGKLAKGMLPU-UHFFFAOYSA-N 0.000 description 1
- JKFYKCYQEWQPTM-UHFFFAOYSA-N 2-azaniumyl-2-(4-fluorophenyl)acetate Chemical compound OC(=O)C(N)C1=CC=C(F)C=C1 JKFYKCYQEWQPTM-UHFFFAOYSA-N 0.000 description 1
- UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 1
- LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 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
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- AJNVAXYYUHFAPJ-UHFFFAOYSA-N B.CP(c1ccccn1)C(C)(C)C Chemical compound B.CP(c1ccccn1)C(C)(C)C AJNVAXYYUHFAPJ-UHFFFAOYSA-N 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 206010061692 Benign muscle neoplasm Diseases 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- 201000005171 Cystadenoma Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 238000006576 Kolbe electrolysis reaction Methods 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- 206010062038 Lip neoplasm Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 201000004458 Myoma Diseases 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
- 206010034811 Pharyngeal cancer Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 239000012891 Ringer solution Substances 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 229910021607 Silver chloride Inorganic materials 0.000 description 1
- 229910021612 Silver iodide Inorganic materials 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- YSMMDNDTGRNTEG-UHFFFAOYSA-M [Cl-].[Au+].C(CP(c1ccccc1)c1ccccn1)P(c1ccccc1)c1ccccn1.C(CP(c1ccccc1)c1ccccn1)P(c1ccccc1)c1ccccn1 Chemical compound [Cl-].[Au+].C(CP(c1ccccc1)c1ccccn1)P(c1ccccc1)c1ccccn1.C(CP(c1ccccc1)c1ccccn1)P(c1ccccc1)c1ccccn1 YSMMDNDTGRNTEG-UHFFFAOYSA-M 0.000 description 1
- JDENQHNGLMCOCF-UHFFFAOYSA-M [Cl-].[Au+].CP(CCP(C)c1ccccc1)c1ccccc1.CP(CCP(C)c1ccccc1)c1ccccc1 Chemical compound [Cl-].[Au+].CP(CCP(C)c1ccccc1)c1ccccc1.CP(CCP(C)c1ccccc1)c1ccccc1 JDENQHNGLMCOCF-UHFFFAOYSA-M 0.000 description 1
- JOYUTRDPOYNART-UHFFFAOYSA-M [I-].[Au+].CC(C)(C)P(CCP(c1ncccn1)C(C)(C)C)c1ncccn1.CC(C)(C)P(CCP(c1ncccn1)C(C)(C)C)c1ncccn1 Chemical compound [I-].[Au+].CC(C)(C)P(CCP(c1ncccn1)C(C)(C)C)c1ncccn1.CC(C)(C)P(CCP(c1ncccn1)C(C)(C)C)c1ncccn1 JOYUTRDPOYNART-UHFFFAOYSA-M 0.000 description 1
- SJRSIZJZTPZWPA-UHFFFAOYSA-M [I-].[Au+].CP(CCP(C)C(C)(C)C)C(C)(C)C.CP(CCP(C)C(C)(C)C)C(C)(C)C Chemical compound [I-].[Au+].CP(CCP(C)C(C)(C)C)C(C)(C)C.CP(CCP(C)C(C)(C)C)C(C)(C)C SJRSIZJZTPZWPA-UHFFFAOYSA-M 0.000 description 1
- DNQUBIBBCMTKMR-UHFFFAOYSA-M [I-].[Au+].CP(CCP(C)c1ccccc1)c1ccccc1.CP(CCP(C)c1ccccc1)c1ccccc1 Chemical compound [I-].[Au+].CP(CCP(C)c1ccccc1)c1ccccc1.CP(CCP(C)c1ccccc1)c1ccccc1 DNQUBIBBCMTKMR-UHFFFAOYSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 208000017733 acquired polycythemia vera Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- BSJGASKRWFKGMV-UHFFFAOYSA-L ammonia dichloroplatinum(2+) Chemical compound N.N.Cl[Pt+2]Cl BSJGASKRWFKGMV-UHFFFAOYSA-L 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000002257 antimetastatic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- BTFJIXJJCSYFAL-UHFFFAOYSA-N arachidyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- KLNFSAOEKUDMFA-UHFFFAOYSA-N azanide;2-hydroxyacetic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OCC(O)=O KLNFSAOEKUDMFA-UHFFFAOYSA-N 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 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 1
- 208000026900 bile duct neoplasm Diseases 0.000 description 1
- 201000009036 biliary tract cancer Diseases 0.000 description 1
- 208000020790 biliary tract neoplasm Diseases 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 208000030381 cutaneous melanoma Diseases 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 201000010175 gallbladder cancer Diseases 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- ZBKIUFWVEIBQRT-UHFFFAOYSA-N gold(1+) Chemical compound [Au+] ZBKIUFWVEIBQRT-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 238000009775 high-speed stirring Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 206010023841 laryngeal neoplasm Diseases 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 201000006721 lip cancer Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 201000009023 maxillary cancer Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 229950007221 nedaplatin Drugs 0.000 description 1
- 208000025189 neoplasm of testis Diseases 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 229940056211 paraffin Drugs 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 1
- ZHUUJSQYXCPING-UHFFFAOYSA-N phosphanyl hydrogen carbonate Chemical compound OC(=O)OP ZHUUJSQYXCPING-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 150000003057 platinum Chemical class 0.000 description 1
- CLSUSRZJUQMOHH-UHFFFAOYSA-L platinum dichloride Chemical compound Cl[Pt]Cl CLSUSRZJUQMOHH-UHFFFAOYSA-L 0.000 description 1
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 description 1
- 208000037244 polycythemia vera Diseases 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- ADZWSOLPGZMUMY-UHFFFAOYSA-M silver bromide Chemical compound [Ag]Br ADZWSOLPGZMUMY-UHFFFAOYSA-M 0.000 description 1
- 229940045105 silver iodide Drugs 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- 201000003708 skin melanoma Diseases 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- PNGLEYLFMHGIQO-UHFFFAOYSA-M sodium;3-(n-ethyl-3-methoxyanilino)-2-hydroxypropane-1-sulfonate;dihydrate Chemical compound O.O.[Na+].[O-]S(=O)(=O)CC(O)CN(CC)C1=CC=CC(OC)=C1 PNGLEYLFMHGIQO-UHFFFAOYSA-M 0.000 description 1
- XEGKKGGYSCPDQK-UHFFFAOYSA-J sodium;tetrachloroplatinum Chemical compound [Na].[Na].Cl[Pt](Cl)(Cl)Cl XEGKKGGYSCPDQK-UHFFFAOYSA-J 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- ZERSMFCGRJUTSA-UHFFFAOYSA-M tert-butyl-[2-[tert-butyl(methyl)phosphanyl]ethyl]-methylphosphane gold(1+) chloride Chemical compound [Cl-].[Au+].CP(CCP(C)C(C)(C)C)C(C)(C)C.CP(CCP(C)C(C)(C)C)C(C)(C)C ZERSMFCGRJUTSA-UHFFFAOYSA-M 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- YODZTKMDCQEPHD-UHFFFAOYSA-N thiodiglycol Chemical compound OCCSCCO YODZTKMDCQEPHD-UHFFFAOYSA-N 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 description 1
- 239000005052 trichlorosilane Substances 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 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
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
- C07F1/005—Compounds containing elements of Groups 1 or 11 of the Periodic Table without C-Metal linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/5027—Polyphosphines
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/5045—Complexes or chelates of phosphines with metallic compounds or metals
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6509—Six-membered rings
- C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/12—All metal or with adjacent metals
- Y10T428/12389—All metal or with adjacent metals having variation in thickness
- Y10T428/12396—Discontinuous surface component
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/12—All metal or with adjacent metals
- Y10T428/12444—Embodying fibers interengaged or between layers [e.g., paper, etc.]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
(R,R)−1,2−ビス(ボラナートtert−ブチル(2−ピリジル)ホスフィノ)エタンおよびラセミ(またはメソ)−1,2−ビス(ボラナートtert−ブチル(2−ピリジル)ホスフィノ)エタンの合成
1H NMR(300.4MHz,CDCl3 );δ=1.09(s,18H),2.07−2.16(m,2H),2.36−2.43(m,2H),7.32−7.37(m,2H),7.73−7.79(m,2H),7.98−8.00(m,2H),8.54−8.55(m,2H)
31P NMR(121.5MHz,CDCl3 );δ=37.9
IR(KBr、cm-1);3045,2965,2931,2901,2869,2368,1573,1456,1425,1065,766
Mass(FAB,POS);m/z 389.(M++H)
カラム;Daicel AD−H,UV波長:254nm,Flow:1.0ml/min.,35℃
移動相;Hex:2−propanol=99:1
(R,R)体:14.8min.,(S,S)体:26.0min.
1H NMR(300.4MHz,CDCl3 );δ=1.06(s,18H),1.71−1.74(m,2H),2.77−2.80(m,2H),7.32−7.36(m,2H),7.71−7.77(m,2H),7.93−7.95(m,2H),8.73−8.74(m,2H)
31P NMR(121.5MHz,CDCl3 );δ=38.4
IR(KBr、cm-1);3054,2971,2930,2903,2869,2382,2351,1571,1425,1067,756
Mass(FAB,POS);m/z 389.(M++H)
ビス(ラセミ−1,2−ビス(tert−ブチル(2−ピリジル)ホスフィノ)エタン)金(I)クロリドの合成
1H NMR(300.4MHz,CDCl3 );δ=0.92(s,18H),1.61−1.80(m,2H),2.32−2.44(m,2H),7.25−8.78(m,8H)
31P NMR(121.5MHz,CDCl3 );δ=12.9
Mass(GC−EI,POS);m/z 303.(M+−tBu)
1H NMR(300.4MHz,CDCl3 );δ=1.20(s,36H),2.6−3.2(m,8H),7.6(m,4H)、8.3(m,4H)、8.5(m,4H)、8.8(m,4H)
31P NMR(121.5MHz,CDCl3 );δ=67.3
Mass(FAB,POS);m/z 917.(M+−Cl- )
ビス(メソ−1,2−ビス(tert−ブチル(2−ピリジル)ホスフィノ)エタン)金(I)クロリドの合成
1H NMR(300.4MHz,CDCl3 );δ=1.20(s,36H),3.10−3.20(m,4H),3.40−3.50(m,4H),7.30−7.34(m,4H),7.76−7.81(m,4H),8.14−8.17(m,4H),8.31−8.34(m,4H)
31P NMR(121.5MHz,CDCl3 );δ= 55.3
Mass(FAB,POS);m/z 917.(M+ −Cl- )
ビス((R,R)−1,2−ビス(tert−ブチル(2−ピリジル)ホスフィノ)エタン)金(I)クロリドの合成
1H NMR(300.4MHz,CDCl3 );δ=1.20(s,36H),3.10−3.20(m,4H),3.40−3.50(m,4H),7.30−7.34(m,4H),7.76−7.81(m,4H),8.14−8.17(m,4H),8.31−8.34(m,4H)
31P NMR(121.5MHz,CDCl3 );δ=55.3
Mass(FAB,POS);m/z 917.(M+ −Cl- )
(同定データ)
1H NMR(300.4MHz,CDCl3)δ=1.20(s,18H),2.25−2.35(m,2H),2.66−2.73(m,2H),7.35−7.39(m,2H),8.82−8.85(m,4H)
31P NMR(121.5MHz,CDCl3);δ=45.5
IR(KBr);2963,2901,2868,2370,2339,1553,1460,1386,1060,767
Mass(FAB,POS);m/z 391.(M++H)
1H NMR(300.4MHz,CDCl3);δ=1.17(s,36H),2.07−2.20(m,4H),2.92−2.95(m,4H),7.40−7.42(m,4H),8.82−8.92(m,8H)
31P NMR(121.5MHz,CDCl3);δ=49.9
Mass(FAB,POS);m/z 922.(M+−Cl−)
(同定データ)
融点;130℃(分解)
1H NMR(CDCl3);δ=1.23(d,JHB=12.2Hz,18H),1.83(m,2H),1.07(m,2H),2.21(m,4H),2.43(m,2H),2.77(m,2H),4.26(s,2H),5.74(d,J=25.1Hz,2H),5.75(d,J=4.6Hz,2H)
31P NMR(1H decoupled,CDCL3);δ=114.8(d,JP−Rh=148Hz),143.7(h,JP−F=711Hz)
IR(KBr);2940,1465,1310,1180,840,560cm−1.
(同定データ)
31P NMR(1H decoupled,CDCL3);δ=−9.2(s),−9.0(s).
(同定データ)
1H NMR(CDCl3);δ=2.2−3.4(m,8H),6.4−7.6(m,32H),8.4−8.6(m,4H)
31PNMR(1H decoupled,CDCL3);δ=21.8−23.4(m);MS(FAB)(M−Cl)+997.
即ちテトラゾリウム塩(3,[4,5−dimethylthiazole−2−yl]−2,5−diphenyltetrazolium bromide,MTT)溶液を加え、さらに3時間、同条件で培養した。細胞内のミトコンドリアの酵素活性により生成したホルマザン結晶を0.04mol/HCl/イオソプロピルアルコールで溶解し、マイクロプレートリーダー(Bio−Rad 550)を用い、595nmの吸光度を測定した。バックグランドを排除するために630nmの吸光度を測定し、実測値から差し引いた。これを生存細胞数として評価し、50%細胞発育抑制濃度(IC50)を算出した。この結果を表2に示す。なお、表2中の値については、化合物1〜3に関しては3回試験を行い、その平均値を示した。また、シスプラチンに関しては2回試験を行い、その平均値を示した。
散剤の製造
顆粒剤の製造
錠剤の製造
カプセル剤の製造
注射剤の製造
ローション剤の製造
軟膏剤の製造
クリーム剤の製造
Claims (5)
- ビス(1,2−ビス(tert−ブチル(2−ピリジル)ホスフィノ)エタン)金(I)クロリド、ビス(1,2−ビス(tert−ブチル(2−ピリミジル)ホスフィノ)エタン)金(I)クロリド、ビス(1,2−ビス(tert−ブチル(2−ピリジル)ホスフィノ)エタン)金(I)ブロミド、ビス(1,2−ビス(tert−ブチル(2−ピリミジル)ホスフィノ)エタン)金(I)ブロミド、ビス(1,2−ビス(tert−ブチル(2−ピリジル)ホスフィノ)エタン)金(I)ヨーダイドまたはビス(1,2−ビス(tert−ブチル(2−ピリミジル)ホスフィノ)エタン)金(I)ヨーダイドである請求項1に記載のホスフィン遷移金属錯体。
- 請求項1または2に記載のホスフィン遷移金属錯体の光学活性体。
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2005352476A JP5015451B2 (ja) | 2005-04-18 | 2005-12-06 | ホスフィン遷移金属錯体、その製造方法およびそれを含有する抗癌剤 |
TW095109586A TW200637868A (en) | 2005-04-18 | 2006-03-21 | The transition-metal complexed phosphines, the manufacturing method of the same, and anti-cancer agents thereof |
US11/911,911 US8106186B2 (en) | 2005-04-18 | 2006-04-17 | Transition metal phosphine complex, method for producing same, and anticancer agent containing transition metal phospine complex |
EP06731964A EP1876182B1 (en) | 2005-04-18 | 2006-04-17 | Phosphine transition metal complex, process for producing the same and anticancer drug containing the same |
PCT/JP2006/308035 WO2006112435A1 (ja) | 2005-04-18 | 2006-04-17 | ホスフィン遷移金属錯体、その製造方法およびそれを含有する抗癌剤 |
CN2006800129660A CN101163710B (zh) | 2005-04-18 | 2006-04-17 | 膦过渡金属配位化合物、其制造方法和含有其的抗癌剂 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2005119404 | 2005-04-18 | ||
JP2005119404 | 2005-04-18 | ||
JP2005352476A JP5015451B2 (ja) | 2005-04-18 | 2005-12-06 | ホスフィン遷移金属錯体、その製造方法およびそれを含有する抗癌剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2006321785A JP2006321785A (ja) | 2006-11-30 |
JP5015451B2 true JP5015451B2 (ja) | 2012-08-29 |
Family
ID=37115150
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2005352476A Expired - Fee Related JP5015451B2 (ja) | 2005-04-18 | 2005-12-06 | ホスフィン遷移金属錯体、その製造方法およびそれを含有する抗癌剤 |
Country Status (6)
Country | Link |
---|---|
US (1) | US8106186B2 (ja) |
EP (1) | EP1876182B1 (ja) |
JP (1) | JP5015451B2 (ja) |
CN (1) | CN101163710B (ja) |
TW (1) | TW200637868A (ja) |
WO (1) | WO2006112435A1 (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009104167A1 (en) * | 2008-02-22 | 2009-08-27 | Mintek | A substance or composition for the treatment of cancer |
WO2011078122A1 (ja) * | 2009-12-21 | 2011-06-30 | 日本化学工業株式会社 | 抗がん剤 |
WO2011078121A1 (ja) * | 2009-12-21 | 2011-06-30 | 日本化学工業株式会社 | 抗がん剤 |
CN102464675A (zh) * | 2010-11-12 | 2012-05-23 | 上海医药工业研究院 | 具有抗肿瘤活性的金络合物及其可药用衍生物 |
US20150266909A1 (en) * | 2014-03-19 | 2015-09-24 | King Abdulaziz City For Science And Technology | Gold(i) complexes with t-butyl phosphine and dialkyl dithiocarbamate ligands |
CN113845545A (zh) * | 2015-07-23 | 2021-12-28 | 赢创运营有限公司 | 用于烷氧基羰基化的丁基-桥连的二膦配体 |
EP3527576B1 (de) * | 2018-02-14 | 2020-11-18 | Evonik Operations GmbH | Propyl-verbrückte diphosphinliganden für die alkoxycarbonylierung |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6110594A (ja) * | 1984-06-04 | 1986-01-18 | スミスクライン・ベツクマン・コーポレイシヨン | ホスフイノ‐炭化水素‐金、銀または銅錯体含有腫瘍細胞成長抑制医薬組成物 |
PH21350A (en) | 1984-06-04 | 1987-10-13 | Smithkline Beckman Corp | Tumor cell growth imhibiting pharmaceutical compositions containing phosphino-hydrocarbon-gold, silver or copper complexes |
US5037812A (en) | 1985-04-02 | 1991-08-06 | Smithkline Beckman Corporation | Tumor cell growth-inhibiting pharmaceutical compositions containing phosphino-hydrocarbon-gold, silver or copper complexes |
NL8502929A (nl) * | 1985-10-25 | 1987-05-18 | Tno | Groep viii-overgangsmetaal-complexen, werkwijze voor het bereiden daarvan, werkwijze voor het bereiden van een geneesmiddel met toepassing van een dergelijke groep viii-overgangsmetaal-complex voor de behandeling van kanker, alsmede aldus verkregen gevormd geneesmiddel. |
CA2207299A1 (en) * | 1994-12-09 | 1996-06-13 | Griffith University | Anti-tumour agents |
-
2005
- 2005-12-06 JP JP2005352476A patent/JP5015451B2/ja not_active Expired - Fee Related
-
2006
- 2006-03-21 TW TW095109586A patent/TW200637868A/zh unknown
- 2006-04-17 CN CN2006800129660A patent/CN101163710B/zh not_active Expired - Fee Related
- 2006-04-17 US US11/911,911 patent/US8106186B2/en not_active Expired - Fee Related
- 2006-04-17 EP EP06731964A patent/EP1876182B1/en not_active Expired - Fee Related
- 2006-04-17 WO PCT/JP2006/308035 patent/WO2006112435A1/ja active Application Filing
Also Published As
Publication number | Publication date |
---|---|
US20090076267A1 (en) | 2009-03-19 |
CN101163710A (zh) | 2008-04-16 |
CN101163710B (zh) | 2011-08-17 |
EP1876182A4 (en) | 2010-05-26 |
EP1876182A1 (en) | 2008-01-09 |
WO2006112435A1 (ja) | 2006-10-26 |
EP1876182B1 (en) | 2012-12-19 |
US8106186B2 (en) | 2012-01-31 |
JP2006321785A (ja) | 2006-11-30 |
TW200637868A (en) | 2006-11-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4476244B2 (ja) | ホスフィン遷移金属錯体、その製造方法及び抗癌剤 | |
JP5015451B2 (ja) | ホスフィン遷移金属錯体、その製造方法およびそれを含有する抗癌剤 | |
HU206220B (en) | Process for producing platinum(ii) complexes and pharmaceutical compositions comprising such compounds as active ingredient | |
JP5090180B2 (ja) | ホスフィン遷移金属錯体、その製造方法およびそれを含有する抗癌剤 | |
KR101955135B1 (ko) | 포스핀 전이 금속 착체를 함유하는 항암제의 제조 방법 | |
JP5161434B2 (ja) | 抗癌剤 | |
JP5646606B2 (ja) | 抗がん剤の製造方法 | |
JP5722233B2 (ja) | 抗がん剤の製造方法 | |
JP5889550B2 (ja) | 抗がん剤組成物 | |
JP6802232B2 (ja) | ホスフィン遷移金属錯体、その製造方法及び抗がん剤 | |
US7390915B1 (en) | Phosphine transition metal complex having ferrocene skeleton, process for making the same, and anti-cancer agent | |
JPH02292292A (ja) | 新規白金錯体および腫瘍治療剤組成物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20081029 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111101 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120104 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120605 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120607 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150615 Year of fee payment: 3 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |