JP2012502970A - 抗腫瘍活性を有する白金錯体 - Google Patents
抗腫瘍活性を有する白金錯体 Download PDFInfo
- Publication number
- JP2012502970A JP2012502970A JP2011527424A JP2011527424A JP2012502970A JP 2012502970 A JP2012502970 A JP 2012502970A JP 2011527424 A JP2011527424 A JP 2011527424A JP 2011527424 A JP2011527424 A JP 2011527424A JP 2012502970 A JP2012502970 A JP 2012502970A
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- JP
- Japan
- Prior art keywords
- platinum
- complexes
- antitumor activity
- cisplatin
- tumor
- 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.)
- Pending
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- 230000000259 anti-tumor effect Effects 0.000 title claims abstract description 10
- 150000003057 platinum Chemical class 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 17
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- 229960004316 cisplatin Drugs 0.000 claims description 10
- 229910052697 platinum Inorganic materials 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 5
- 239000007787 solid Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 102000004506 Blood Proteins Human genes 0.000 description 3
- 108010017384 Blood Proteins Proteins 0.000 description 3
- 241000282414 Homo sapiens Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 description 3
- JKOCEVIXVMBKJA-UHFFFAOYSA-M silver;butanoate Chemical compound [Ag+].CCCC([O-])=O JKOCEVIXVMBKJA-UHFFFAOYSA-M 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 241000282412 Homo Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 125000003963 dichloro group Chemical group Cl* 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229920000768 polyamine Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- UOFGSWVZMUXXIY-UHFFFAOYSA-N 1,5-Diphenyl-3-thiocarbazone Chemical compound C=1C=CC=CC=1N=NC(=S)NNC1=CC=CC=C1 UOFGSWVZMUXXIY-UHFFFAOYSA-N 0.000 description 1
- 238000004294 195Pt NMR spectroscopy Methods 0.000 description 1
- 101710134784 Agnoprotein Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010061968 Gastric neoplasm Diseases 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920001410 Microfiber Polymers 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 190000008236 carboplatin Chemical compound 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical group O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960005399 satraplatin Drugs 0.000 description 1
- 190014017285 satraplatin Chemical compound 0.000 description 1
- MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0086—Platinum compounds
- C07F15/0093—Platinum compounds without a metal-carbon linkage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
本発明の目的は、抗腫瘍活性を有する白金錯体、その調製方法、それを含有する医薬組成物、および腫瘍病変の治療に有用な医薬品の調製のためのその使用である。
白金錯体は、化学療法剤の中でも固形腫瘍の治療に効果が高い。特に、シスプラチン[cis−ジクロロジアミン白金(II)、CDDP]は、高頻度で使用され高い効果を有する抗腫瘍剤の1つであるが、いくつかの重度の副作用を生じることにより投与が制限されている。その上、この医薬品に耐性のある腫瘍細胞は頻繁に発生し、固形腫瘍(例えば、肺、結腸−直腸の腫瘍、および胃の腫瘍)の大部分は、シスプラチンまたは他の化学療法剤に反応しない(E.Wong,C.M.Giandomenico,Current Status of Platinum−Based Antitumor Drugs,Chem.Rev.1999,99,2451−2466)(非特許文献1)。
本発明は、式(I)の[μ−(1,8,11,18−テトラアザオクタデカン−N1,N18)ビス[trans−ジアミン(ブチラト−O)白金(II)]]四硝酸塩
計算値 C24.64% H3.62%
実測値 C24.62% H3.60%
1H NMR(DMSO−d6):δ 2.07(2H,t,J=7.28Hz);1.51(2H,dt,J=7.29,7.31);0.87(3H,t,J=7.36)。
元素分析
計算値 C23.16% H5.48% N14.73% Pt34.19%
実測値 C21.95% H5.17% N13.93% Pt32.84%
MS:1103.0、[MH+C3F7COOH−4HNO3]+
1H NMR(D2O):δ 3.93(2H,s);3.33(4H,s);3.05(4H,t,J=7.68Hz);2.62(4H,m);2.24(4H,t,J=7.40);1.68(8H,m);1.53(4H,m);1.40(8H,m);0.87(6H,t,J=7.41)。
195Pt NMR(D2O):δ −2167.70。
Claims (6)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI2008A001660 | 2008-09-18 | ||
IT001660A ITMI20081660A1 (it) | 2008-09-18 | 2008-09-18 | Complesso di platino ad attivita' antitumorale |
PCT/IB2009/006974 WO2010032131A1 (en) | 2008-09-18 | 2009-09-16 | Platinum complex with antitumor activity |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2012502970A true JP2012502970A (ja) | 2012-02-02 |
Family
ID=40852422
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011527424A Pending JP2012502970A (ja) | 2008-09-18 | 2009-09-16 | 抗腫瘍活性を有する白金錯体 |
Country Status (10)
Country | Link |
---|---|
US (1) | US20130018096A1 (ja) |
EP (1) | EP2344512B1 (ja) |
JP (1) | JP2012502970A (ja) |
CN (1) | CN102159585A (ja) |
AU (1) | AU2009294311B2 (ja) |
CA (1) | CA2737683C (ja) |
ES (1) | ES2401553T3 (ja) |
IT (1) | ITMI20081660A1 (ja) |
PL (1) | PL2344512T3 (ja) |
WO (1) | WO2010032131A1 (ja) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002512589A (ja) * | 1996-07-22 | 2002-04-23 | エフ.ホフマン―ラ ロシュ アーゲー | 抗腫瘍剤としてのポリアミン配位子を有する新規ビス―プラチナ錯体 |
JP2005501123A (ja) * | 2001-08-22 | 2005-01-13 | ヴァージニア コモンウェルス ユニバーシティ | プロドラッグとしての標的ビス白金ポリアミド:白金の選択的放出 |
WO2007071415A1 (en) * | 2005-12-22 | 2007-06-28 | Cell Therapeutics, Inc. - Sede Secondaria | Bis-platinum complexes with antitumor activity |
-
2008
- 2008-09-18 IT IT001660A patent/ITMI20081660A1/it unknown
-
2009
- 2009-09-16 EP EP09737474A patent/EP2344512B1/en not_active Not-in-force
- 2009-09-16 US US13/119,278 patent/US20130018096A1/en not_active Abandoned
- 2009-09-16 PL PL09737474T patent/PL2344512T3/pl unknown
- 2009-09-16 WO PCT/IB2009/006974 patent/WO2010032131A1/en active Application Filing
- 2009-09-16 ES ES09737474T patent/ES2401553T3/es active Active
- 2009-09-16 CA CA2737683A patent/CA2737683C/en not_active Expired - Fee Related
- 2009-09-16 AU AU2009294311A patent/AU2009294311B2/en not_active Ceased
- 2009-09-16 CN CN2009801366402A patent/CN102159585A/zh active Pending
- 2009-09-16 JP JP2011527424A patent/JP2012502970A/ja active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002512589A (ja) * | 1996-07-22 | 2002-04-23 | エフ.ホフマン―ラ ロシュ アーゲー | 抗腫瘍剤としてのポリアミン配位子を有する新規ビス―プラチナ錯体 |
JP2005501123A (ja) * | 2001-08-22 | 2005-01-13 | ヴァージニア コモンウェルス ユニバーシティ | プロドラッグとしての標的ビス白金ポリアミド:白金の選択的放出 |
WO2007071415A1 (en) * | 2005-12-22 | 2007-06-28 | Cell Therapeutics, Inc. - Sede Secondaria | Bis-platinum complexes with antitumor activity |
Also Published As
Publication number | Publication date |
---|---|
CA2737683A1 (en) | 2010-03-25 |
AU2009294311B2 (en) | 2014-11-27 |
ITMI20081660A1 (it) | 2010-03-19 |
WO2010032131A1 (en) | 2010-03-25 |
CA2737683C (en) | 2016-11-01 |
EP2344512B1 (en) | 2012-12-19 |
ES2401553T3 (es) | 2013-04-22 |
PL2344512T3 (pl) | 2013-06-28 |
US20130018096A1 (en) | 2013-01-17 |
CN102159585A (zh) | 2011-08-17 |
EP2344512A1 (en) | 2011-07-20 |
AU2009294311A1 (en) | 2010-03-25 |
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