JP2006520360A - シクロブタン−1,1−ジカルボキシレートリガンドを有する白金錯体の蛋白結合誘導体 - Google Patents
シクロブタン−1,1−ジカルボキシレートリガンドを有する白金錯体の蛋白結合誘導体 Download PDFInfo
- Publication number
- JP2006520360A JP2006520360A JP2006504734A JP2006504734A JP2006520360A JP 2006520360 A JP2006520360 A JP 2006520360A JP 2006504734 A JP2006504734 A JP 2006504734A JP 2006504734 A JP2006504734 A JP 2006504734A JP 2006520360 A JP2006520360 A JP 2006520360A
- Authority
- JP
- Japan
- Prior art keywords
- group
- platinum complex
- methoxybenzyl
- cyclobutane
- bis
- 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.)
- Granted
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- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 20
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 20
- CCQPAEQGAVNNIA-UHFFFAOYSA-L cyclobutane-1,1-dicarboxylate(2-) Chemical compound [O-]C(=O)C1(C([O-])=O)CCC1 CCQPAEQGAVNNIA-UHFFFAOYSA-L 0.000 title abstract description 9
- 150000003057 platinum Chemical class 0.000 title abstract description 7
- 239000003446 ligand Substances 0.000 title abstract description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 44
- 229910052697 platinum Inorganic materials 0.000 claims description 20
- 239000000243 solution Substances 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- -1 4-methoxybenzyl-protected cyclobutane-1,1-dicarboxylic acid Chemical class 0.000 claims description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 9
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 8
- CCQPAEQGAVNNIA-UHFFFAOYSA-N cyclobutane-1,1-dicarboxylic acid Chemical class OC(=O)C1(C(O)=O)CCC1 CCQPAEQGAVNNIA-UHFFFAOYSA-N 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 239000004971 Cross linker Substances 0.000 claims description 6
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 claims description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims description 6
- OQKBMOJOFCPVDR-UHFFFAOYSA-N bis[(4-methoxyphenyl)methyl] 3-hydroxycyclobutane-1,1-dicarboxylate Chemical compound C1=CC(OC)=CC=C1COC(=O)C1(C(=O)OCC=2C=CC(OC)=CC=2)CC(O)C1 OQKBMOJOFCPVDR-UHFFFAOYSA-N 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 claims description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 4
- INXKQYBPTOGHAL-UHFFFAOYSA-N bis[(4-methoxyphenyl)methyl] propanedioate Chemical compound C1=CC(OC)=CC=C1COC(=O)CC(=O)OCC1=CC=C(OC)C=C1 INXKQYBPTOGHAL-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 125000004185 ester group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 claims description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical group NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 2
- 230000003213 activating effect Effects 0.000 claims description 2
- 125000004069 aziridinyl group Chemical group 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 150000001990 dicarboxylic acid derivatives Chemical class 0.000 claims description 2
- 125000002228 disulfide group Chemical group 0.000 claims description 2
- ZBKFYXZXZJPWNQ-UHFFFAOYSA-N isothiocyanate group Chemical group [N-]=C=S ZBKFYXZXZJPWNQ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- HGBRVNPNABYSEN-UHFFFAOYSA-N COC1=CC=C(CC(CC(C=C2)=CC=C2OC)(C2)CC2O)C=C1 Chemical compound COC1=CC=C(CC(CC(C=C2)=CC=C2OC)(C2)CC2O)C=C1 HGBRVNPNABYSEN-UHFFFAOYSA-N 0.000 claims 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims 1
- 241000051616 Ulmus minor Species 0.000 claims 1
- OFGVFMBIEFTXBK-UHFFFAOYSA-N [1-bromo-2-(2-bromopropan-2-yl)-3,3-dimethylbutoxy]silane Chemical compound BrC(C(C(Br)(C)C)C(C)(C)C)O[SiH3] OFGVFMBIEFTXBK-UHFFFAOYSA-N 0.000 claims 1
- 125000005396 acrylic acid ester group Chemical group 0.000 claims 1
- 239000012752 auxiliary agent Substances 0.000 claims 1
- UAPFZVLLGBIQMV-UHFFFAOYSA-N bis[(4-methoxyphenyl)methyl] 3-[tert-butyl(dimethyl)silyl]oxycyclobutane-1,1-dicarboxylate Chemical compound C1=CC(OC)=CC=C1COC(=O)C1(C(=O)OCC=2C=CC(OC)=CC=2)CC(O[Si](C)(C)C(C)(C)C)C1 UAPFZVLLGBIQMV-UHFFFAOYSA-N 0.000 claims 1
- 239000008063 pharmaceutical solvent Substances 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
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- 235000018102 proteins Nutrition 0.000 description 15
- 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 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
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- 239000000741 silica gel Substances 0.000 description 10
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 102000004506 Blood Proteins Human genes 0.000 description 6
- 108010017384 Blood Proteins Proteins 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 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 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
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- 239000007787 solid Substances 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
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- 241001465754 Metazoa Species 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 3
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- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
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- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 description 2
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- DCHMUKQFWXHICT-UHFFFAOYSA-N 3-[3-[2-(2,5-dioxopyrrol-1-yl)ethoxy]propanoyl]cyclobutane-1,1-dicarboxylic acid Chemical compound C1C(C(=O)O)(C(O)=O)CC1C(=O)CCOCCN1C(=O)C=CC1=O DCHMUKQFWXHICT-UHFFFAOYSA-N 0.000 description 1
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- 229920001059 synthetic polymer Polymers 0.000 description 1
- RTSDRESZEDGONS-UHFFFAOYSA-N tert-butyl(1,3-dibromopropan-2-yloxy)silane Chemical compound CC(C)(C)[SiH2]OC(CBr)CBr RTSDRESZEDGONS-UHFFFAOYSA-N 0.000 description 1
- ZJQJJPACPLHZFT-UHFFFAOYSA-N tert-butyl-(1,3-dibromopropan-2-yloxy)-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OC(CBr)CBr ZJQJJPACPLHZFT-UHFFFAOYSA-N 0.000 description 1
- BQJJSYAFFLGSEY-UHFFFAOYSA-N tert-butyl-dimethyl-propan-2-yloxysilane Chemical compound CC(C)O[Si](C)(C)C(C)(C)C BQJJSYAFFLGSEY-UHFFFAOYSA-N 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
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- 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
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Abstract
Description
抗腫瘍作用のある白金錯体は一般式II
X=OHまたはNH2を表す]の作用物質誘導体である。該錯体は、シクロブタン環にヒドロキシ基またはアミノ基が存在することにより、ならびに場合により、キレート化するアミンリガンド、たとえばトランス−1,2−ジアミノシクロヘキサン、シス−1,2−ジアミノシクロヘキサン、エチレンジアミンまたは1,3−ジアミノプロパンが存在することにより臨床的な標準カルボプラチンから区別される。
第一工程でビス(4−メトキシベンジル)マロネートを1,3−ジブロモ−2−t−ブチルシロキシプロパンによりジアルキル化し、これによりシクロブタン環構造が生じる。
ビス(4−メトキシベンジル)−3−t−ブチルジメチル−シロキシシクロブタン−1,1−ジカルボキシレート(PMB−CB−OTBS)の製造
ビス(4−メトキシベンジル)−3−ヒドロキシシクロブタン−1,1−ジ−カルボキシレート(PMB−CB−OH)の製造
ビス(4−メトキシベンジル)−3−(6−マレインイミド−4−オキサカプロイル)シクロブタン−1,1−ジカルボキシレート(PMB−CB−1−Mal)の製造
3−(6−マレインイミド−4−オキサカプロイル)シクロブタン−1,1−ジ−カルボン酸(COOH−CB−1−Mal)の製造
トランス−(R,R/S,S)−シクロヘキサン−1,2−ジアミノ白金(II)−[3−(6−マレインイミド−4−オキサカプロイル)シクロブタン−1,1−ジカルボキシレート](DACH−Pt−CB−1−Mal)の製造
1H−NMR(CD3OD):
δ=0.97〜1.29(m、4H、シクロヘキシル−H)、1.38〜1.56(m、2H、シクロヘキシル−H)、1.81〜1.96(m、2H、シクロヘキシル−H)、2.19〜2.36(m、2H、シクロヘキシル−H)、2.42(t、J=5.9Hz、CH 2COO)、2.60〜2.79(m、2H、CH 2CHOR)、3.27〜3.41(m、2H、CH 2CHOR)、3.46〜3.66(m、6H、NCH 2、OCH 2)、4.67〜4.86(m、1H、CHOR)、6.76(s、2H、C(O)CH=CHCO)。
13C−NMR(CD3OD):
δ=25.51、33.30(シクロヘキシル)、35.92(CH2COO)、38.17(NCH2)、39.80/40.09(CH2CHOR)、51.35(C(COOH)2)、63.81/63.86(シクロヘキシル−NH2)、65.66(CHOR)、67.22、68.65(OCH2)、135.50(C(O)CH=CHCO)、172.52、172.80(C(O)CH=CHCO、CH2 COO)、180.41、180.61(C(COOH)2)。
ESI−MS(4.0kV、MeOH):
m/z(%)663.0([M+1]+、100)。
ジアンミン白金(II)−[3−(6−マレインイミド−4−オキサカプロイル)シクロブタン−1,1−ジカルボキシレート]((NH3)2−Pt−CB−1−Mal)の製造
ESI−MS:
m/z(%)581.8([M]+、100)。
ビス(4−メトキシベンジル)−3−(15−マレインイミド−4,7,10,13−テトロキサペンタデカノイル)シクロブタン−1,1−ジカルボキシレート(PMB−CB−4−Mal)の製造
3−(15−マレインイミド−4,7,10,13−テトロキサペンタデカノイル)シクロブタン−1,1−ジカルボン酸(COOH−CB−4−Mal)の製造
トランス−(R,R/S,S)−シクロヘキサン−1,2−ジアミノ白金(II)−[3−(15−マレインイミド−4,7,10,13−テトロキサペンタデカノイル)シクロ−ブタン−1,1−ジカルボキシレート](DACH−Pt−CB−4−Mal)の製造
1H−NMR(D2O、アセトンで検定、δ=2.20ppm):
δ=0.98〜1.35(m、4H、シクロヘキシル−H)、1.44〜1.62(m、2H、シクロヘキシル−H)、1.94〜2.06(m、2H、シクロヘキシル−H)、2.28〜2.48(m、2H、シクロヘキシル−H)、2.66(t、J=6.0Hz、CH 2COO)、2.80〜2.93(m、2H、CH 2CHOR)、3.34〜3.50(m、2H、CH 2CHOR)、3.54〜3.84(m、18H、NCH 2、OCH 2)、4.93(′p′、J=7.1Hz、1H、CHOR)、6.85(s、2H、C(O)CH=CHCO)。
13C−NMR(D2O、アセトンで検定):
δ=24.30、32.22(シクロヘキシル)、34.91(CH2COO)、37.37(NCH2)、38.54/38.72(CH2CHOR)、50.71(C(COOH)2)、63.05/63.09(シクロヘキシル−NH2)、65.37(CHOR)、66.52、68.02、69.73、69.97、70.01(OCH2)、134.86(C(O)CH=CHCO)、173.39、174.11(C(O)CH=CHCO、CH2CCOO)、180.30、180.47(C(COOH)2)。
195Pt−NMR(D2O):δ=−311。
IR(KBr):v=3448(ss、b)、2939(w、b)、1709(ss)、1627(s)、1353(m)、1094(ss、b)、696(w)cm−1。
ESI−MS(4.0kV、MeOH):m/z(%)816.9([M+Na]+、100)。
C24H41N3O12Pt[794.71]
元素分析:計算値:C:40.81%、H:5.20%、N:5.29%、
測定値:C:39.88%、H:5.16%、N:5.08%。
インビボでのDACH−Pt−CB−1−Malの有効性
図1に記載されている生物学的データは、カルボプラチンと比較して、DACH−Pt−CB−1−Malの高められたインビボ有効性を明示している。
治療:DACH−Pt−CB−1−Mal(75および100mg/kg)ならびにカルボプラチン(100mg/kg)、7日目に1回、カルボプラチン(75mg/kg)はそのつど7日目および14日目;i.v.(カルボプラチンおよび誘導体をそのつど0.15 0.3mL グルコース−ホスフェート−バッファ pH6.5)。
Claims (15)
- PMが、マレインイミド基、2−ジチオピリジル基、ハロゲンアセトアミド基、ハロゲンアセテート基、ジスルフィド基、アクリル酸エステル基、モノアルキルマレイン酸エステル基、モノアルキルマレアミン酸アミド基、N−ヒドロキシスクシンイミジルエステル基、イソチオシアネート基またはアジリジン基であり、これらは置換されていていてもよい、請求項1記載の白金錯体。
- PMがマレインイミド基であり、置換されていてもよい、請求項2記載の白金錯体。
- m<2およびn=1〜4である、請求項3記載の白金錯体。
- X=OおよびY=Oである、請求項4記載の白金錯体。
- カルボン酸活性化試薬として、N,N′−ジシクロヘキシルカルボジイミド、N,N′−ジイソプロピルカルボジイミドまたは(ベンゾトリアゾール−1−イルオキシ)トリス(ジメチルアミノ)ホスホニウム−ヘキサフルオロ−ホスフェート、最も有利には2−クロロ−1−メチルピリジニウムヨージドを使用する、請求項8記載の方法。
- ビス(4−メトキシベンジル)−3−t−ブチルジメチルシロキシシクロブタン−1,1−ジ−カルボキシレートを、テトラブチルアンモニウムフルオリドと反応させることにより、ビス(4−メトキシベンジル)−3−ヒドロキシシクロブタン−1,1−ジカルボキシレートが得られる、請求項8記載の方法。
- ビス(4−メトキシベンジル)マロネートを、1,3−ジブロモ−2−t−ブチルジメチル−シロキシプロパンと反応させることにより、ビス(4−メトキシベンジル)−3−t−ブチルジメチルシロキシシクロ−ブタン−1,1−ジ−カルボキシレートが得られる、請求項11記載の方法。
- 作用物質として請求項1から5までのいずれか1項記載の白金錯体を、場合により通常の助剤および/または製薬溶剤と共に含有する薬剤。
- 癌疾患を治療するための請求項1から5までのいずれか1項記載の白金錯体の使用。
- 請求項1から5までのいずれか1項記載の化合物を治療のために認容可能な溶液にすることを特徴とする、癌疾患を治療するための薬剤の製造方法。
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DE10314780A DE10314780A1 (de) | 2003-03-19 | 2003-03-19 | Proteinbindende Derivate von Platinkomplexen mit Cyclobutan-1,1-dicarboxylatliganden |
DE10314780.2 | 2003-03-19 | ||
PCT/EP2004/002850 WO2004083223A1 (de) | 2003-03-19 | 2004-03-18 | Proteinbindende derivate von platinkomplexen mit cyclobutan-1,1-dicarboxylatliganden |
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JP2013529219A (ja) * | 2010-06-04 | 2013-07-18 | オハイオ ユニバーシティー | ホスファプラチン、及び癌治療のためのそれらの使用 |
WO2014203691A1 (ja) * | 2013-06-18 | 2014-12-24 | 株式会社ヤクルト本社 | 白金錯体を含有する新規医薬 |
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GB0321613D0 (en) * | 2003-09-15 | 2003-10-15 | Drug Discovery Lab As | Compounds |
US7208611B2 (en) * | 2005-02-23 | 2007-04-24 | Xenoport, Inc. | Platinum-containing compounds exhibiting cytostatic activity, synthesis and methods of use |
RS62412B1 (sr) | 2015-12-09 | 2021-10-29 | Univ Wien Med | Jedinjenja platine funkcionalizovana sa monomaleimidom za terapiju raka |
CN114163479A (zh) * | 2020-09-11 | 2022-03-11 | 上海海聚生物科技有限公司 | 一类治疗癌症用的铂类化合物及其制备方法 |
US20230339997A1 (en) * | 2020-09-11 | 2023-10-26 | Shanghai Haiju Biological Technology Co., Ltd. | Class of platinum compounds for treating cancer, and method for preparation thereof |
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WO2004006859A2 (en) * | 2002-07-16 | 2004-01-22 | Sonus Pharmaceuticals, Inc. | Platinum compound |
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JP2013529219A (ja) * | 2010-06-04 | 2013-07-18 | オハイオ ユニバーシティー | ホスファプラチン、及び癌治療のためのそれらの使用 |
US9688709B2 (en) | 2010-06-04 | 2017-06-27 | Ohio University | Phosphaplatins and their use for treatment of cancers |
US10364264B2 (en) | 2010-06-04 | 2019-07-30 | Ohio University | Proliferative disease treatment methods with phosphaplatin complexes |
US10385083B2 (en) | 2010-06-04 | 2019-08-20 | Ohio University | Phosphaplatin complexes and methods for treatment of proliferative diseases using the phosphaplatin complexes |
US10759820B2 (en) | 2010-06-04 | 2020-09-01 | Ohio University | Proliferative disease treatment methods with phosphaplatin complexes |
WO2014203691A1 (ja) * | 2013-06-18 | 2014-12-24 | 株式会社ヤクルト本社 | 白金錯体を含有する新規医薬 |
JPWO2014203691A1 (ja) * | 2013-06-18 | 2017-02-23 | 株式会社ヤクルト本社 | 白金錯体を含有する新規医薬 |
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ATE371664T1 (de) | 2007-09-15 |
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