CN103732601B - 一类治疗细胞增殖性疾病的铂化合物、其制备方法和应用 - Google Patents
一类治疗细胞增殖性疾病的铂化合物、其制备方法和应用 Download PDFInfo
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- CN103732601B CN103732601B CN201280023124.0A CN201280023124A CN103732601B CN 103732601 B CN103732601 B CN 103732601B CN 201280023124 A CN201280023124 A CN 201280023124A CN 103732601 B CN103732601 B CN 103732601B
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- 238000011282 treatment Methods 0.000 title claims abstract description 29
- 150000003058 platinum compounds Chemical class 0.000 title claims description 41
- 238000002360 preparation method Methods 0.000 title abstract description 14
- 208000035269 cancer or benign tumor Diseases 0.000 title abstract description 3
- 229940045985 antineoplastic platinum compound Drugs 0.000 title description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 161
- 150000003839 salts Chemical class 0.000 claims abstract description 96
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 59
- 201000011510 cancer Diseases 0.000 claims abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- -1 2- (2-methylaminoethyl) -malonic acid Chemical compound 0.000 claims description 106
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 44
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 42
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 41
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 40
- UMWYYMCOBYVEPY-UHFFFAOYSA-N azanide;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2] UMWYYMCOBYVEPY-UHFFFAOYSA-N 0.000 claims description 39
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 38
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 38
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 35
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 34
- 125000000623 heterocyclic group Chemical group 0.000 claims description 34
- 229940095064 tartrate Drugs 0.000 claims description 34
- 125000003545 alkoxy group Chemical group 0.000 claims description 31
- 239000003814 drug Substances 0.000 claims description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 claims description 24
- 229910019142 PO4 Inorganic materials 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical group 0.000 claims description 23
- RONYZDHQLMCCPT-UHFFFAOYSA-N 2-[2-(diethylamino)ethyl]propanedioic acid Chemical compound CCN(CC)CCC(C(O)=O)C(O)=O RONYZDHQLMCCPT-UHFFFAOYSA-N 0.000 claims description 21
- 239000010452 phosphate Substances 0.000 claims description 21
- 229910052697 platinum Inorganic materials 0.000 claims description 21
- NSIOVSFHZDVKJL-UHFFFAOYSA-N 2-[3-(diethylamino)propyl]propanedioic acid Chemical compound CCN(CC)CCCC(C(O)=O)C(O)=O NSIOVSFHZDVKJL-UHFFFAOYSA-N 0.000 claims description 19
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- IBBXBZXYKDZWRS-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]propanedioic acid Chemical compound CN(C)CCC(C(O)=O)C(O)=O IBBXBZXYKDZWRS-UHFFFAOYSA-N 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 230000002062 proliferating effect Effects 0.000 claims description 16
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 16
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 125000004429 atom Chemical group 0.000 claims description 10
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- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 10
- IAKVGIHOIMVUCF-UHFFFAOYSA-N 2-[2-(dipropylamino)ethyl]propanedioic acid Chemical compound CCCN(CCC)CCC(C(O)=O)C(O)=O IAKVGIHOIMVUCF-UHFFFAOYSA-N 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 239000007924 injection Substances 0.000 claims description 8
- 238000002347 injection Methods 0.000 claims description 8
- VHCQWQAYVBRQQC-QWWZWVQMSA-N (1r,2r)-cyclobutane-1,2-diamine Chemical compound N[C@@H]1CC[C@H]1N VHCQWQAYVBRQQC-QWWZWVQMSA-N 0.000 claims description 7
- XCBSSBHYECISNJ-UHFFFAOYSA-N 2-[3-(dimethylamino)propyl]propanedioic acid Chemical compound CN(C)CCCC(C(O)=O)C(O)=O XCBSSBHYECISNJ-UHFFFAOYSA-N 0.000 claims description 7
- QSESKLPHKFGBGR-UHFFFAOYSA-N 2-[3-(dipropylamino)propyl]propanedioic acid Chemical compound CCCN(CCC)CCCC(C(O)=O)C(O)=O QSESKLPHKFGBGR-UHFFFAOYSA-N 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 6
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 6
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 5
- 229910002651 NO3 Inorganic materials 0.000 claims description 5
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 5
- NHNBFGGVMKEFGY-UHFFFAOYSA-N nitrate group Chemical group [N+](=O)([O-])[O-] NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 5
- ZINLSRVIVCBSJM-UHFFFAOYSA-N 2-(2-aminoethyl)propanedioic acid Chemical compound NCCC(C(O)=O)C(O)=O ZINLSRVIVCBSJM-UHFFFAOYSA-N 0.000 claims description 4
- PZVQUWLMTNOMFN-UHFFFAOYSA-N 2-(3-piperidin-1-ylpropyl)propanedioic acid Chemical compound OC(=O)C(C(O)=O)CCCN1CCCCC1 PZVQUWLMTNOMFN-UHFFFAOYSA-N 0.000 claims description 4
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 4
- 229940009098 aspartate Drugs 0.000 claims description 4
- 229940077388 benzenesulfonate Drugs 0.000 claims description 4
- 229930195712 glutamate Natural products 0.000 claims description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 4
- RENPTINIWHSECZ-UHFFFAOYSA-N 2-(3-aminopropyl)propanedioic acid Chemical compound NCCCC(C(O)=O)C(O)=O RENPTINIWHSECZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 claims description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 claims description 2
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- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 claims description 2
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- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
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- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
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- 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
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Landscapes
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CN201280023124.0A CN103732601B (zh) | 2011-07-09 | 2012-07-06 | 一类治疗细胞增殖性疾病的铂化合物、其制备方法和应用 |
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CN201110192289.8 | 2011-07-09 | ||
CN2011101922898 | 2011-07-09 | ||
CN201280023124.0A CN103732601B (zh) | 2011-07-09 | 2012-07-06 | 一类治疗细胞增殖性疾病的铂化合物、其制备方法和应用 |
PCT/CN2012/078302 WO2013007172A1 (zh) | 2011-07-09 | 2012-07-06 | 一类治疗细胞增殖性疾病的铂化合物、其制备方法和应用 |
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CN201280023124.0A Active CN103732601B (zh) | 2011-07-09 | 2012-07-06 | 一类治疗细胞增殖性疾病的铂化合物、其制备方法和应用 |
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US (1) | US9138421B2 (zh) |
EP (1) | EP2740738B1 (zh) |
JP (1) | JP5914648B2 (zh) |
KR (2) | KR20140040848A (zh) |
CN (2) | CN102863474A (zh) |
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WO2014075391A1 (zh) * | 2012-11-17 | 2014-05-22 | 北京市丰硕维康技术开发有限责任公司 | 离去基团是含氨基或烷氨基的丙二酸衍生物的铂类化合物 |
WO2014114183A1 (zh) * | 2013-01-23 | 2014-07-31 | 北京市丰硕维康技术开发有限责任公司 | 一种治疗肿瘤细胞增生性疾病的铂(ii)类化合物 |
AU2016284816B2 (en) * | 2015-06-25 | 2021-10-07 | Syn-Nat Products Enterprise LLC | Pharmaceutical co-crystal composition and use thereof |
CN112533935B (zh) * | 2018-09-01 | 2023-01-13 | 北京硕佰医药科技有限责任公司 | 一种铂类化合物磷酸盐及其制备方法 |
CN116023232B (zh) * | 2023-01-03 | 2024-03-08 | 湖南省湘中制药有限公司 | 一种丙基丙二酸及其同系物的制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1698903A (zh) * | 2005-05-25 | 2005-11-23 | 北京市海格里斯科技有限公司 | 一种高分子抗肿瘤顺铂药物及其制备方法 |
WO2006091790A1 (en) * | 2005-02-23 | 2006-08-31 | Xenoport, Inc. | Platinum-containing compounds exhibiting cytostatic activity, synthesis and methods of use |
CN101475600A (zh) * | 2009-01-20 | 2009-07-08 | 昆明贵研药业有限公司 | 一种合成抗肿瘤药物卡铂的新方法 |
Family Cites Families (36)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4322362A (en) | 1980-07-28 | 1982-03-30 | Bristol-Myers Company | Salts of 2-hydroxymalonate platinum complexes |
JPS61249993A (ja) | 1985-04-26 | 1986-11-07 | Tanabe Seiyaku Co Ltd | 新規有機白金錯体及びその製法 |
IL85595A0 (en) | 1987-03-06 | 1988-08-31 | Tanabe Seiyaku Co | Organic platinum complex and its preparation |
US4946954A (en) | 1989-01-17 | 1990-08-07 | Georgetown University | Platinum pharmaceutical agents |
DE4138042C2 (de) | 1991-11-19 | 1993-10-14 | Biotechnolog Forschung Gmbh | Epothilone, deren Herstellungsverfahren sowie diese Verbindungen enthaltende Mittel |
JPH06137794A (ja) | 1992-10-27 | 1994-05-20 | Toray Ind Inc | リバーシブル偽装衣 |
ES2178093T5 (es) | 1995-11-17 | 2009-02-16 | Gesellschaft Fur Biotechnologische Forschung Mbh (Gbf) | Derivados de epotilon y su preparacion. |
US6011029A (en) | 1996-02-26 | 2000-01-04 | Bristol-Myers Squibb Company | Inhibitors of farnesyl protein transferase |
PT941227E (pt) | 1996-11-18 | 2004-08-31 | Biotechnolog Forschung Mbh Gbf | Epothilona d sua preparacao e sua utilizacao como agente citostatico ou como agente de proteccao fitossanitaria |
JP4579351B2 (ja) | 1996-12-03 | 2010-11-10 | スローン−ケッタリング インスティトュート フォア キャンサー リサーチ | エポチロンの合成とその中間体及びその類似物並びにその使用 |
US6441186B1 (en) | 1996-12-13 | 2002-08-27 | The Scripps Research Institute | Epothilone analogs |
US6380394B1 (en) | 1996-12-13 | 2002-04-30 | The Scripps Research Institute | Epothilone analogs |
CN1128803C (zh) | 1997-02-25 | 2003-11-26 | 生物技术研究有限公司(Gbf) | 环氧噻嗪酮b-n-氧化物及其制备方法 |
GB9801231D0 (en) | 1997-06-05 | 1998-03-18 | Merck & Co Inc | A method of treating cancer |
WO1999002224A1 (en) | 1997-07-07 | 1999-01-21 | Lewis Robert D | Statistical analysis and feedback system for sports employing a projectile |
US6605599B1 (en) | 1997-07-08 | 2003-08-12 | Bristol-Myers Squibb Company | Epothilone derivatives |
JP2001510189A (ja) | 1997-07-16 | 2001-07-31 | シエーリング アクチエンゲゼルシヤフト | チアゾール誘導体、その製造法および使用 |
JP2001512723A (ja) | 1997-08-09 | 2001-08-28 | シエーリング アクチエンゲゼルシヤフト | 新規エポチロン誘導体、その製法およびその薬学的使用 |
US6040321A (en) | 1997-11-12 | 2000-03-21 | Bristol-Myers Squibb Company | Aminothiazole inhibitors of cyclin dependent kinases |
US6365749B1 (en) | 1997-12-04 | 2002-04-02 | Bristol-Myers Squibb Company | Process for the preparation of ring-opened epothilone intermediates which are useful for the preparation of epothilone analogs |
JP4434484B2 (ja) | 1997-12-04 | 2010-03-17 | ブリストル−マイヤーズ スクイブ カンパニー | オキシラニルエポチロン化合物のオレフィン性エポチロン化合物への還元法 |
MXPA00008365A (es) | 1998-02-25 | 2002-11-07 | Sloan Kettering Inst Cancer | Sintesis de epotilonas, intermediarios y analogos de las mismas. |
US6399638B1 (en) | 1998-04-21 | 2002-06-04 | Bristol-Myers Squibb Company | 12,13-modified epothilone derivatives |
US6498257B1 (en) | 1998-04-21 | 2002-12-24 | Bristol-Myers Squibb Company | 2,3-olefinic epothilone derivatives |
DE19826988A1 (de) | 1998-06-18 | 1999-12-23 | Biotechnolog Forschung Gmbh | Epothilon-Nebenkomponenten |
WO1999067253A2 (en) | 1998-06-22 | 1999-12-29 | Novartis Ag | Desmethyl epothilones |
AU5036999A (en) | 1998-06-30 | 2000-01-17 | Schering Aktiengesellschaft | Epothilon derivatives, their preparation process, intermediate products and their pharmaceutical use |
US6262094B1 (en) | 1999-02-22 | 2001-07-17 | Bristol-Myers Squibb Company | C-21 modified epothilones |
US7166733B2 (en) * | 2000-01-04 | 2007-01-23 | Access Pharmaceuticals, Inc. | O,O'-Amidomalonate and N,O-Amidomalonate platinum complexes |
KR20040074857A (ko) | 2003-02-19 | 2004-08-26 | 학교법인 이화학당 | N-치환 아미노디카복실산의 백금(ⅱ) 착물 및 그 제조방법 |
CN1680384A (zh) * | 2004-04-08 | 2005-10-12 | 香港中文大学 | 去甲基斑蟊素铂配合物及其用途 |
KR20110126644A (ko) | 2009-01-31 | 2011-11-23 | 아이쥐에프 온콜로지, 엘엘씨 | 항암 단백질-백금 결합체 |
US8901337B2 (en) * | 2009-07-16 | 2014-12-02 | Royal College Of Surgeons In Ireland | Metal complexes having dual histone deacetylase inhibitory and DNA-binding activity |
CN102276674A (zh) | 2011-06-24 | 2011-12-14 | 天津大学 | 用于肿瘤靶向治疗的含半乳糖铂配合物及其制备方法 |
CN102286050A (zh) | 2011-06-24 | 2011-12-21 | 天津大学 | 用于肿瘤靶向治疗的含葡萄糖铂配合物及其制备方法 |
CN102276657A (zh) | 2011-06-24 | 2011-12-14 | 天津大学 | 用于肿瘤靶向治疗的含甘露糖铂配合物及其制备方法 |
-
2011
- 2011-07-09 CN CN2011101922898A patent/CN102863474A/zh active Pending
-
2012
- 2012-07-06 KR KR1020147003050A patent/KR20140040848A/ko active Application Filing
- 2012-07-06 KR KR1020167026055A patent/KR101739083B1/ko active IP Right Grant
- 2012-07-06 JP JP2014519389A patent/JP5914648B2/ja active Active
- 2012-07-06 WO PCT/CN2012/078302 patent/WO2013007172A1/zh active Application Filing
- 2012-07-06 EP EP12811424.6A patent/EP2740738B1/en active Active
- 2012-07-06 US US14/131,902 patent/US9138421B2/en active Active
- 2012-07-06 CN CN201280023124.0A patent/CN103732601B/zh active Active
- 2012-07-06 ES ES12811424.6T patent/ES2668470T3/es active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006091790A1 (en) * | 2005-02-23 | 2006-08-31 | Xenoport, Inc. | Platinum-containing compounds exhibiting cytostatic activity, synthesis and methods of use |
CN1698903A (zh) * | 2005-05-25 | 2005-11-23 | 北京市海格里斯科技有限公司 | 一种高分子抗肿瘤顺铂药物及其制备方法 |
CN101475600A (zh) * | 2009-01-20 | 2009-07-08 | 昆明贵研药业有限公司 | 一种合成抗肿瘤药物卡铂的新方法 |
Non-Patent Citations (2)
Title |
---|
Anthraquinone intercalators as carrier molecules or second-generation platinum anticancer drugs;D Gibson等,;《Eur J Med Chem》;19971231;第32卷;第823-831页 * |
The Relevance of Polar Surface Area (PSA) in Rationalizing Biological Properties of Several cis-Diamminemalonatoplatinum(II) Derivatives;Giulia Caron等,;《ChemMedChem》;20091231;第4卷;第1677-1685页,尤其是1678页图1、1680页图3 * |
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US20140142079A1 (en) | 2014-05-22 |
KR20140040848A (ko) | 2014-04-03 |
ES2668470T3 (es) | 2018-05-18 |
JP2014523905A (ja) | 2014-09-18 |
KR101739083B1 (ko) | 2017-05-23 |
JP5914648B2 (ja) | 2016-05-11 |
WO2013007172A1 (zh) | 2013-01-17 |
EP2740738B1 (en) | 2018-03-28 |
CN103732601A (zh) | 2014-04-16 |
CN102863474A (zh) | 2013-01-09 |
KR20160113333A (ko) | 2016-09-28 |
EP2740738A4 (en) | 2015-03-04 |
US9138421B2 (en) | 2015-09-22 |
EP2740738A1 (en) | 2014-06-11 |
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