DK168387B1 - Cis-Platinkomplekser, deres fremstilling og mellemprodukter til fremstilling heraf - Google Patents
Cis-Platinkomplekser, deres fremstilling og mellemprodukter til fremstilling heraf Download PDFInfo
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- DK168387B1 DK168387B1 DK464787A DK464787A DK168387B1 DK 168387 B1 DK168387 B1 DK 168387B1 DK 464787 A DK464787 A DK 464787A DK 464787 A DK464787 A DK 464787A DK 168387 B1 DK168387 B1 DK 168387B1
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- 239000000543 intermediate Substances 0.000 title claims description 8
- 238000004519 manufacturing process Methods 0.000 title 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 67
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 16
- 238000002360 preparation method Methods 0.000 claims abstract description 16
- -1 oxalic Chemical class 0.000 claims abstract description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 10
- 229910002651 NO3 Inorganic materials 0.000 claims abstract description 8
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 4
- 150000007524 organic acids Chemical class 0.000 claims abstract description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims abstract description 3
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- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims abstract description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 45
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 5
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- LOTBYPQQWICYBB-UHFFFAOYSA-N methyl n-hexyl-n-[2-(hexylamino)ethyl]carbamate Chemical compound CCCCCCNCCN(C(=O)OC)CCCCCC LOTBYPQQWICYBB-UHFFFAOYSA-N 0.000 description 1
- PYISNMAFHKCJSV-UHFFFAOYSA-N n-[1-azido-2-(azidomethyl)-3-hydroxypropan-2-yl]acetamide Chemical compound [N-]=[N+]=NCC(CO)(NC(=O)C)CN=[N+]=[N-] PYISNMAFHKCJSV-UHFFFAOYSA-N 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
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- 239000008194 pharmaceutical composition Substances 0.000 description 1
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- CLSUSRZJUQMOHH-UHFFFAOYSA-L platinum dichloride Chemical class Cl[Pt]Cl CLSUSRZJUQMOHH-UHFFFAOYSA-L 0.000 description 1
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- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
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- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical class NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H23/00—Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19863630497 DE3630497A1 (de) | 1986-09-08 | 1986-09-08 | Cis-platin-komplexe, verfahren zu ihrer herstellung und diese verbindungen enthaltende pharmazeutische mittel |
DE3630497 | 1986-09-08 |
Publications (3)
Publication Number | Publication Date |
---|---|
DK464787D0 DK464787D0 (da) | 1987-09-07 |
DK464787A DK464787A (da) | 1988-03-09 |
DK168387B1 true DK168387B1 (da) | 1994-03-21 |
Family
ID=6309120
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK464787A DK168387B1 (da) | 1986-09-08 | 1987-09-07 | Cis-Platinkomplekser, deres fremstilling og mellemprodukter til fremstilling heraf |
Country Status (15)
Country | Link |
---|---|
US (1) | US5091521A (es) |
EP (1) | EP0263956B1 (es) |
JP (1) | JPS6368546A (es) |
AT (1) | ATE68500T1 (es) |
AU (1) | AU611394B2 (es) |
CA (1) | CA1313655C (es) |
DE (2) | DE3630497A1 (es) |
DK (1) | DK168387B1 (es) |
ES (1) | ES2039220T3 (es) |
FI (1) | FI86304C (es) |
GR (1) | GR3003522T3 (es) |
MX (1) | MX8132A (es) |
NO (1) | NO174055C (es) |
PT (1) | PT85655B (es) |
ZA (1) | ZA876619B (es) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU593608B2 (en) * | 1986-10-07 | 1990-02-15 | Board Of Regents, The University Of Texas System | Hydrophobic CIS-platinum complexes efficiently incorporated into liposomes |
DK252688A (da) * | 1987-05-08 | 1988-11-09 | Sankyo Co | Antitumorplatinkomplekser, fremgangsmaade til fremstilling deraf, samt deres terapeutiske anvendelse |
US4956459A (en) * | 1987-07-17 | 1990-09-11 | Georgetown University | Platinum compounds suitable for use as pharmaceuticals |
IT1216687B (it) * | 1988-04-01 | 1990-03-08 | Boehringer Biochemia Srl | Complessi di platino (ii), loro preparazione e impiego come antitumorali. |
DE3834098A1 (de) * | 1988-10-07 | 1990-04-19 | Behringwerke Ag | Cis-platin-komplexe mit einem 1,3-diaminopropan-derivat als liganden, verfahren zu ihrer herstellung und diese verbindung enthaltende pharmazeutische mittel |
US5871710A (en) * | 1992-09-04 | 1999-02-16 | The General Hospital Corporation | Graft co-polymer adducts of platinum (II) compounds |
AU2701395A (en) * | 1994-06-27 | 1996-01-19 | General Hospital Corporation, The | Graft co-polymer adducts of platinum (ii) compounds |
US5760480A (en) * | 1995-09-20 | 1998-06-02 | Advanced Micro Devics, Inc. | Low RC interconnection |
US6235782B1 (en) | 1998-11-12 | 2001-05-22 | Rifat Pamukcu | Method for treating a patient with neoplasia by treatment with a platinum coordination complex |
US6235776B1 (en) | 1998-11-12 | 2001-05-22 | Cell Pathways, Inc. | Method for treating a patient with neoplasia by treatment with a paclitaxel derivative |
WO2006091790A1 (en) * | 2005-02-23 | 2006-08-31 | Xenoport, Inc. | Platinum-containing compounds exhibiting cytostatic activity, synthesis and methods of use |
JP5579618B2 (ja) * | 2007-12-07 | 2014-08-27 | プラナ バイオテクノロジー リミティッド | 治療および診断用化合物 |
CN109293927A (zh) | 2009-02-04 | 2019-02-01 | 布里格姆及妇女医院股份有限公司 | 纳米级铂化合物及其使用方法 |
EP3109325B1 (en) | 2010-08-24 | 2018-12-26 | Dana-Farber Cancer Institute, Inc. | Methods for predicting anti-cancer response |
WO2012174378A2 (en) | 2011-06-17 | 2012-12-20 | Myriad Genetics, Inc. | Methods and materials for assessing allelic imbalance |
BR112014015152A2 (pt) | 2011-12-21 | 2017-07-04 | Myriad Genetics Inc | métodos e materiais para a avaliação da perda de heterozigosidade |
ES2687024T3 (es) | 2012-02-23 | 2018-10-23 | Children's Medical Center Corporation | Procedimientos para predecir la respuesta contra el cáncer |
CA3190075A1 (en) | 2012-06-07 | 2013-12-12 | Institut Curie | Methods for detecting inactivation of the homologous recombination pathway (brca1/2) in human tumors |
US10308986B2 (en) | 2013-03-14 | 2019-06-04 | Children's Medical Center Corporation | Cancer diagnosis, treatment selection and treatment |
WO2015086473A1 (en) | 2013-12-09 | 2015-06-18 | Institut Curie | Methods for detecting inactivation of the homologous recombination pathway (brca1/2) in human tumors |
EP3180447B1 (en) | 2014-08-15 | 2020-03-11 | Myriad Genetics, Inc. | Methods and materials for assessing homologous recombination deficiency |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL7807334A (nl) * | 1978-07-06 | 1980-01-08 | Tno | Platina-diaminecomplexen, werkwijze voor het bereiden daarvan, werkwijze voor het bereiden van een genees- middel met toepassing van een dergelijk platina-dia- minecomplex voor de behandeling van kanker, alsmede al- dus verkregen gevormd geneesmiddel. |
NL8204067A (nl) * | 1982-10-21 | 1984-05-16 | Tno | Platina-diaminecomplexen, werkwijze voor het bereiden daarvan, werkwijze voor het bereiden van een geneesmiddel met toepassing van een dergelijk platinadiaminecomplex voor de behandeling van kanker, alsmede aldus verkregen gevormd geneesmiddel. |
US4500465A (en) * | 1982-06-28 | 1985-02-19 | Engelhard Corporation | Solubilized platinum (II) complexes |
DE3503620A1 (de) * | 1984-06-30 | 1986-01-23 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung von 1-azidoaldosen |
DE3432320A1 (de) * | 1984-09-03 | 1986-03-13 | Behringwerke Ag, 3550 Marburg | Cis-platin-komplexe mit einem pentaerythritderivat als liganden, verfahren zu ihrer herstellung und diese verbindungen enthaltendes pharmazeutisches mittel |
JPS6259294A (ja) * | 1985-09-09 | 1987-03-14 | Ajinomoto Co Inc | 白金錯体および抗腫瘍剤 |
US4760157A (en) * | 1986-01-31 | 1988-07-26 | American Cyanamid Company | (2,2,-bis(aminomethyl)-1,3-propanediol-N,N')platinum complexes |
-
1986
- 1986-09-08 DE DE19863630497 patent/DE3630497A1/de not_active Withdrawn
-
1987
- 1987-09-02 AT AT87112768T patent/ATE68500T1/de not_active IP Right Cessation
- 1987-09-02 DE DE8787112768T patent/DE3773829D1/de not_active Expired - Lifetime
- 1987-09-02 ES ES198787112768T patent/ES2039220T3/es not_active Expired - Lifetime
- 1987-09-02 EP EP87112768A patent/EP0263956B1/de not_active Expired - Lifetime
- 1987-09-04 ZA ZA876619A patent/ZA876619B/xx unknown
- 1987-09-04 CA CA000546144A patent/CA1313655C/en not_active Expired - Fee Related
- 1987-09-04 FI FI873841A patent/FI86304C/fi not_active IP Right Cessation
- 1987-09-07 PT PT85655A patent/PT85655B/pt not_active IP Right Cessation
- 1987-09-07 JP JP62222163A patent/JPS6368546A/ja active Pending
- 1987-09-07 MX MX813287A patent/MX8132A/es unknown
- 1987-09-07 DK DK464787A patent/DK168387B1/da active
- 1987-09-07 NO NO873721A patent/NO174055C/no unknown
- 1987-09-07 AU AU78103/87A patent/AU611394B2/en not_active Ceased
-
1990
- 1990-08-28 US US07/576,185 patent/US5091521A/en not_active Expired - Fee Related
-
1992
- 1992-01-08 GR GR910401654T patent/GR3003522T3/el unknown
Also Published As
Publication number | Publication date |
---|---|
NO174055C (no) | 1994-03-09 |
DE3773829D1 (de) | 1991-11-21 |
US5091521A (en) | 1992-02-25 |
EP0263956A2 (de) | 1988-04-20 |
JPS6368546A (ja) | 1988-03-28 |
ES2039220T3 (es) | 1993-09-16 |
FI86304C (fi) | 1992-08-10 |
CA1313655C (en) | 1993-02-16 |
DK464787D0 (da) | 1987-09-07 |
FI873841A0 (fi) | 1987-09-04 |
EP0263956B1 (de) | 1991-10-16 |
AU7810387A (en) | 1988-03-10 |
ATE68500T1 (de) | 1991-11-15 |
PT85655A (de) | 1987-10-01 |
DE3630497A1 (de) | 1988-03-10 |
NO174055B (no) | 1993-11-29 |
FI873841A (fi) | 1988-03-09 |
ZA876619B (en) | 1988-04-27 |
NO873721D0 (no) | 1987-09-07 |
GR3003522T3 (es) | 1993-03-16 |
FI86304B (fi) | 1992-04-30 |
EP0263956A3 (en) | 1988-10-05 |
AU611394B2 (en) | 1991-06-13 |
PT85655B (pt) | 1990-05-31 |
DK464787A (da) | 1988-03-09 |
NO873721L (no) | 1988-03-09 |
MX8132A (es) | 1994-02-28 |
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