EP0448583A1 - Organometallische verbindungen, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzungen - Google Patents
Organometallische verbindungen, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzungenInfo
- Publication number
- EP0448583A1 EP0448583A1 EP90900160A EP90900160A EP0448583A1 EP 0448583 A1 EP0448583 A1 EP 0448583A1 EP 90900160 A EP90900160 A EP 90900160A EP 90900160 A EP90900160 A EP 90900160A EP 0448583 A1 EP0448583 A1 EP 0448583A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- formula
- group
- carbon atoms
- acid
- compound
- 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.)
- Withdrawn
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 12
- 238000000034 method Methods 0.000 title claims description 10
- 150000002902 organometallic compounds Chemical class 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 44
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 21
- 229910052787 antimony Inorganic materials 0.000 claims abstract description 15
- WATWJIUSRGPENY-UHFFFAOYSA-N antimony atom Chemical compound [Sb] WATWJIUSRGPENY-UHFFFAOYSA-N 0.000 claims abstract description 15
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 12
- 229910052785 arsenic Inorganic materials 0.000 claims abstract description 10
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 claims abstract description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
- 239000011593 sulfur Substances 0.000 claims abstract description 8
- 239000002253 acid Substances 0.000 claims description 16
- 230000015572 biosynthetic process Effects 0.000 claims description 10
- 238000003786 synthesis reaction Methods 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 4
- HJSJHFXDUMCZEC-UHFFFAOYSA-N dichloroarsenic Chemical compound Cl[As]Cl HJSJHFXDUMCZEC-UHFFFAOYSA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 125000001302 tertiary amino group Chemical group 0.000 claims description 4
- 201000006353 Filariasis Diseases 0.000 claims description 3
- 201000002311 trypanosomiasis Diseases 0.000 claims description 3
- 208000004554 Leishmaniasis Diseases 0.000 claims description 2
- 206010035664 Pneumonia Diseases 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 229910006069 SO3H Inorganic materials 0.000 abstract 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 208000000230 African Trypanosomiasis Diseases 0.000 description 4
- 208000030852 Parasitic disease Diseases 0.000 description 4
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- JCYZMTMYPZHVBF-UHFFFAOYSA-N Melarsoprol Chemical class NC1=NC(N)=NC(NC=2C=CC(=CC=2)[As]2SC(CO)CS2)=N1 JCYZMTMYPZHVBF-UHFFFAOYSA-N 0.000 description 3
- 241000223095 Trypanosoma evansi Species 0.000 description 3
- 239000013067 intermediate product Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000239183 Filaria Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- XKNKHVGWJDPIRJ-UHFFFAOYSA-N arsanilic acid Chemical compound NC1=CC=C([As](O)(O)=O)C=C1 XKNKHVGWJDPIRJ-UHFFFAOYSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 150000004683 dihydrates Chemical class 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 229960001728 melarsoprol Drugs 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- -1 p-arsonoanilino Chemical group 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 239000002690 trypanocidal agent Substances 0.000 description 2
- 230000000654 trypanocidal effect Effects 0.000 description 2
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 1
- VHJLVAABSRFDPM-UHFFFAOYSA-N 1,4-dithiothreitol Chemical compound SCC(O)C(O)CS VHJLVAABSRFDPM-UHFFFAOYSA-N 0.000 description 1
- SRZXCOWFGPICGA-UHFFFAOYSA-N 1,6-Hexanedithiol Chemical compound SCCCCCCS SRZXCOWFGPICGA-UHFFFAOYSA-N 0.000 description 1
- PGTWZHXOSWQKCY-UHFFFAOYSA-N 1,8-Octanedithiol Chemical compound SCCCCCCCCS PGTWZHXOSWQKCY-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010024769 Local reaction Diseases 0.000 description 1
- 206010035660 Pneumocystis Infections Diseases 0.000 description 1
- 241000233872 Pneumocystis carinii Species 0.000 description 1
- 241001442399 Trypanosoma brucei gambiense Species 0.000 description 1
- 241001442397 Trypanosoma brucei rhodesiense Species 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- SMTOKHQOVJRXLK-UHFFFAOYSA-N butane-1,4-dithiol Chemical compound SCCCCS SMTOKHQOVJRXLK-UHFFFAOYSA-N 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 150000004662 dithiols Chemical group 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000029080 human African trypanosomiasis Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- KMTUBAIXCBHPIZ-UHFFFAOYSA-N pentane-1,5-dithiol Chemical compound SCCCCCS KMTUBAIXCBHPIZ-UHFFFAOYSA-N 0.000 description 1
- ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 201000002612 sleeping sickness Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- OUFRIWNNMFWZTM-UHFFFAOYSA-M sodium arsanilate Chemical compound [Na+].NC1=CC=C([As](O)([O-])=O)C=C1 OUFRIWNNMFWZTM-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000005406 washing Methods 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/90—Antimony compounds
- C07F9/92—Aromatic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- 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
- C07F9/66—Arsenic compounds
- C07F9/70—Organo-arsenic compounds
Definitions
- the present invention relates to organometallic compounds, their methods of preparation, as well as pharmaceutical compositions comprising said compounds.
- a more particular subject of the invention is the use of these pharmaceutical compositions in the treatment of parasitic diseases such as trypanoso iases and filariasis.
- the compound Mel B discovered by E. FRIEDHEIM (patent deposited in the UNITED STATES and published in 1953 under the number 2,659,723), is the drug most used for the treatment of human trypanosomiasis in the second stage.
- this compound has many drawbacks, one of the most serious of which is the triggering of unpredictable lethal encephalopathies which occur in 5% of individuals treated with Mel B (WHO / FAO EXPERT COMMITY (1979), The African Trypanosomiases. WHO TECHNICAL REPORT SERIES, N 635).
- This patent also describes other compounds related to Mel B having an arsenic (As) or antimony (Sb) atom engaged in a pentacyclic structure.
- a process capable of leading to the production of a derivative related to Mel B in which an antimony atom is engaged in a hexacyclic structure, is described by way of example in this patent.
- the compound Mel W (FRIEDHEIM E.A.H (1966) German patent No. 1,229,543) is a water-soluble derivative of Mel B, and has been used in veterinary and human therapy. However, the latter application was discontinued due to numerous toxicity issues.
- the two drugs, Mel B and Mel W, are similar compounds of the dithiarsolane type with 5 vertices (pentacycle); the only structural difference between these two compounds is a different substituent on the pentacycle.
- the synthesis of this pentacycle is carried out from vicinal dithiols (that is to say carried by two neighboring carbon atoms).
- the present invention relates to the organometallic compounds represented by the following general formula:
- - M represents arsenic (As) or antimony (Sb),
- - RR 2 , R 3 , R ⁇ and g identical or different, represent: . a hydrogen atom,
- a primary amine-NH 2 or a secondary or tertiary amino substituted by one or two al groups of 1 to 18 carbon atoms,. a group of formula O
- ⁇ ⁇ represents a methyl -CH 3 or an amine -NH 2 ,
- X represents a nitrogen atom or a CH group
- - A T represents an alkylene group of 3 to 21 carbon atoms, in particular of 4 to 6 carbon atoms, this alkylene group being, where appropriate, substituted:. either by a group of formula - (CH 2 ) n -R 7 in which R 7 represents a hydrogen atom, or a hydroxyl function -OH, or acid -COOH, or amino -NH 2 , or sulfonic -SO 3 H , and n represents an integer varying from 0 to 10, or by several identical or different groups of formula - (CH 2 ) n -R 7 mentioned above,.
- the present invention relates more particularly to the compounds represented by the following general formula:
- - M represents arsenic (As) or antimony (Sb),
- - R represents a hydrogen atom or a group of the following formula:
- H - A represents an alkylene group of 1 to 18 carbon atoms, in particular of 2 to 4 carbon atoms, optionally substituted by one or more, hydroxyl function (s), - OH.
- the subject of the invention is more particularly the following compounds:
- the present invention also relates to the process for obtaining the compounds defined above, comprising the reaction between - on the one hand the compound of formula
- R ,, R 2 , R 3 , ⁇ and 5 have the meanings indicated above
- M represents an oxide, or acid form, or acid salt, or arsenic dichloride (As) or d 'antimony (Sb), - and on the other hand the compound of formula HY-A ⁇ ZH in which Y, A 1 and Z have the meanings indicated above, followed by the recovery and the purification of the compounds obtained.
- a more particular subject of the present invention is the process for obtaining the specific compounds defined above, comprising the reaction between - on the one hand the compound of formula
- R has the meaning indicated above and M represents an oxide, or acid, or acid salt, or arsenic dichloride (As) or antimony (Sb) form,
- the invention also relates to the use of the compounds defined above, including the derivative of formula (I) mentioned above, for obtaining medicaments intended for the treatment of trypanosomiasis, leishmaniases, diseases caused by filaria ( filariasis), and Pneumocystis carinii infections, especially in people with AIDS.
- compositions comprising one or more of the trypanocidal compounds defined above, including the derivative of formula (I) mentioned above, in combination with a phar aceutically acceptable vehicle.
- compositions are particularly effective for the treatment of parasitic diseases such as those caused by trypanosomes, notably sleeping sickness, and by filaria; these compositions also seem to be particularly effective for the treatment of other diseases such as pneumonia caused by Pneumocystis carinii.
- the compounds of the invention are combined with a pharmaceutically acceptable vehicle in the form of a suspension in a physiological liquid for intramuscular or subcutaneous administration.
- a pharmaceutically acceptable vehicle in the form of a suspension in a physiological liquid for intramuscular or subcutaneous administration.
- Such compositions are particularly advantageous compared to current trypanocidal drugs such as Mel B, the latter being administered in an irritating organic solvent causing painful inflammations which limits its use.
- compositions of the invention can be used for the purpose of preventing or treating parasitic diseases mentioned above in humans or animals (veterinary application).
- compositions have also been found to be active against strains of melarsoprol-resistant trypanosomes (Mel B).
- the compounds of the invention are much less toxic than the derivatives arsenic or antimony trypanocides currently used.
- Example 1 The invention is more particularly illustrated with the aid of the following examples: Example 1:
- the synthesis is carried out from diamino-4,6-chloro-2-s-triazine which is condensed by reflux with p-arsanilic acid (Banks).
- the last step of this synthesis can also be carried out in an aqueous medium.
- mice infected with Trypanosoma evansi or T. evansi
- the trypanosomes from the blood are eliminated within 24 hours with a dose of 5 mg / kg of the derivative of the invention described above by subcutaneous injection or with a dose 2.5 mg / kg by intramuscular injection.
- mice with T.gambiense the trypanosomes from the blood are eliminated within 48 hours with a dose of 5 mg / kg of the abovementioned derivative of the invention by subcutaneous or intramuscular injection.
- the parasite ie obtained by infection of mice with a T. rhodesiense strain resistant to melarsoprol, disappears after three days using an intramuscular dose of 10 mg / kg.
- prophylaxis of approximately 12 days is obtained against T. evansi.
- the drug is well tolerated; the treated mice show no local reaction or any clinical sign of toxicity of the central nervous system after subcutaneous injection up to 500 mg / kg.
- the product obtained which is in the form of easily sprayable white flakes, is p-aminophenyl-2-dithiarsepane-1,3,2-diol-5,6.
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8816406A FR2640269B1 (fr) | 1988-12-13 | 1988-12-13 | Composes organometalliques, leurs modes de preparation et compositions pharmaceutiques les contenant |
| FR8816406 | 1988-12-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0448583A1 true EP0448583A1 (de) | 1991-10-02 |
Family
ID=9372892
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP90900160A Withdrawn EP0448583A1 (de) | 1988-12-13 | 1989-12-13 | Organometallische verbindungen, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzungen |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US5281588A (de) |
| EP (1) | EP0448583A1 (de) |
| JP (1) | JPH04502311A (de) |
| FR (1) | FR2640269B1 (de) |
| WO (1) | WO1990006931A1 (de) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2684382B1 (fr) * | 1991-12-02 | 1994-10-21 | Rhone Merieux | Medicaments et preparations pures de dichlorhydrate de melarsomine, leur procede d'obtention et produits intermediaires obtenus. |
| US6191123B1 (en) * | 1999-03-19 | 2001-02-20 | Parker Hughes Institute | Organic-arsenic compounds |
| AUPQ296799A0 (en) * | 1999-09-20 | 1999-10-14 | Unisearch Limited | A cell-membrane impermeable trivalent organoarsenical derivative and use thereof |
| JP4571408B2 (ja) * | 2002-01-07 | 2010-10-27 | ボード・オブ・リージエンツ，ザ・ユニバーシテイ・オブ・テキサス・システム | 癌治療薬としての、ｓ−ジメチルアルシノ−チオコハク酸、ｓ−ジメチルアルシノ−２−チオ安息香酸、ｓ−（ジメチルアルシノ）グルタチオン |
| KR100483195B1 (ko) * | 2002-08-12 | 2005-04-14 | 배일주 | 육산화사비소를 유효성분으로 함유하는 사상충증예방·치료용 약제학적 조성물 |
| EP1563099B1 (de) * | 2002-11-07 | 2009-07-22 | Newsouth Innovations Pty Limited | Induktion der mitochondrialen permeabilitätstransition |
| US6686344B1 (en) | 2003-01-30 | 2004-02-03 | Paker Hughes Institute | Organic-arsonic compounds |
| US8268883B2 (en) | 2006-11-01 | 2012-09-18 | Newsouth Innovations Pty Limited | Organo-arsenoxide compounds and use thereof |
| CN114835753B (zh) * | 2022-05-07 | 2023-05-12 | 厦门大学 | 一种光裂解砷-巯基标签化合物及其应用 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA627057A (en) * | 1961-09-12 | A.H. Friedheim Ernst | Dimercapto derivatives of organic compounds | |
| US2659723A (en) * | 1947-01-28 | 1953-11-17 | Ernst A H Friedheim | Triazine organometallic compounds and process for preparing same |
| GB655435A (en) * | 1947-01-28 | 1951-07-18 | Ernst Albert Hermann Friedheim | Organo arsenic and antimony compounds |
| US2664432A (en) * | 1947-01-28 | 1953-12-29 | Ernst A H Friedheim | Heterocyclic metal and sulfur organic compounds |
| US3035052A (en) * | 1959-03-02 | 1962-05-15 | Ernst A H Friedheim | Arsenic-containing derivatives of dimercapto-succinic acid |
| JPS5888627A (ja) * | 1981-11-20 | 1983-05-26 | Horiba Ltd | 非接触型工腔温度計 |
| US4602642A (en) * | 1984-10-23 | 1986-07-29 | Intelligent Medical Systems, Inc. | Method and apparatus for measuring internal body temperature utilizing infrared emissions |
| JPS61138130A (ja) * | 1984-12-10 | 1986-06-25 | Matsushita Electric Works Ltd | 体温計 |
-
1988
- 1988-12-13 FR FR8816406A patent/FR2640269B1/fr not_active Expired - Fee Related
-
1989
- 1989-12-13 US US07/689,275 patent/US5281588A/en not_active Expired - Fee Related
- 1989-12-13 WO PCT/EP1989/001541 patent/WO1990006931A1/fr not_active Application Discontinuation
- 1989-12-13 JP JP2500800A patent/JPH04502311A/ja active Pending
- 1989-12-13 EP EP90900160A patent/EP0448583A1/de not_active Withdrawn
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9006931A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH04502311A (ja) | 1992-04-23 |
| WO1990006931A1 (fr) | 1990-06-28 |
| FR2640269A1 (fr) | 1990-06-15 |
| FR2640269B1 (fr) | 1991-03-15 |
| US5281588A (en) | 1994-01-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FR2678622A1 (fr) | Nouveaux complexes de vanadium, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. | |
| FR2696740A1 (fr) | Dérivés prodrogués de la diméthylbiguanide et applications comme médicaments. | |
| EP0022118A1 (de) | Sulfonyl-anilin-Derivate, Verfahren zu ihrer Herstellung und ihre therapeutische Verwendung | |
| EP0448583A1 (de) | Organometallische verbindungen, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzungen | |
| CA1213892A (fr) | Procede de preparation de nouveaux derives de la sulfonyluree | |
| EP0632026B1 (de) | Alpha Aminosäurederivate, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen | |
| FR2795412A1 (fr) | Nouveaux derives d'ammonium quaternaire, leur procede de preparation et les compositions pharmaceutiques qui les contiennent | |
| CH661661A5 (fr) | Agent antineoplasique. | |
| EP0143016B1 (de) | Derivate von 4-(3-Alkynyloxy-2-hydroxy-propyl)-piperazin-1-yl-N-phenylacetamid, ihre Herstellung und ihre therapeutische Verwendung | |
| EP0133096B1 (de) | Synergistine Derivate, deren Herstellung und diese enthaltende pharmazeutische Zusammensetzungen | |
| EP0772630B1 (de) | Streptograminderivate, ihre herstellung und sie enthaltende pharmazeutische zubereitungen | |
| EP0138684A2 (de) | 2-(N-Pyrrolidino)-3-isobutoxy-N-phenyl substituierte N-Benzylpropylamine, ihre Herstellung und ihre pharmazeutische Anwendung | |
| EP0482993A1 (de) | N,O-Spirocyclische Cyclotriphosphazen-Derivate, ihre Herstellung und ihre therapeutische Verwendung | |
| FR2558160A1 (fr) | 3-alkoxy 2-(n-pyrrolidino)-n-pyrimidinyl ou -pyrazinyl propylamines, leur preparation et leur application en therapeutique | |
| BE856403A (fr) | Derives d'imidazole-4-carboxamide 5-0-acyles, procede pour leur preparation et medicaments en contenant | |
| EP0430800B1 (de) | Substituierte Benzothiazolinone, ihre Herstellung und sie enthaltende pharmazeutische Zusammenstellungen | |
| EP0389338A1 (de) | Platinkomplexe, ihre Herstellung und pharmazeutische Zusammensetzungen, die sie enthalten | |
| FR2572730A1 (fr) | Nouveaux derives de l'arsenic, leur preparation et leur application, notamment comme medicaments antiparasitaires | |
| EP0226475A1 (de) | Diphenoxyethylaminderivate, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Zusammensetzungen | |
| EP1569642A1 (de) | Verwendung von canthin-6-on, von pflanzenextrakten dieses enthaltend und von dessen derivaten für die behandlung von trypanosomiasis | |
| EP0347305A1 (de) | [(Aryl-4-piperazinyl-1)-2-ethoxy]-3p-cymole, die ortho-, meta-, para-monosubstituierten oder disubstituierten Derivate, das Verfahren zu deren Herstellung und die als aktives Prinzip diese Verbindungen enthaltenden Arzneimittel | |
| JPH06345739A (ja) | ２−ニトロイミダゾール−１−イル−ｎ−プロパルギルアセトアミド | |
| FR2716454A1 (fr) | Nouveaux dérivés de 4-aminométhyl 3-diméthylamino acridines substituées, leur préparation et leur application thérapeutique. | |
| FR2491926A1 (fr) | Derives de raubasine, leur preparation et leur application en therapeutique | |
| BE819146A (fr) | Nouveaux derives pyrimidiniques et leur procede de preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 19910601 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE ES FR GB IT LI LU NL SE |
|
| 17Q | First examination report despatched |
Effective date: 19920729 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
| 18D | Application deemed to be withdrawn |
Effective date: 19981224 |