IE832459L - Platinum diamine complexes. - Google Patents
Platinum diamine complexes.Info
- Publication number
- IE832459L IE832459L IE832459A IE245983A IE832459L IE 832459 L IE832459 L IE 832459L IE 832459 A IE832459 A IE 832459A IE 245983 A IE245983 A IE 245983A IE 832459 L IE832459 L IE 832459L
- Authority
- IE
- Ireland
- Prior art keywords
- platinum
- formula
- group
- diamine complex
- diamine
- Prior art date
Links
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 title claims description 26
- 229910052697 platinum Inorganic materials 0.000 title claims description 20
- -1 Platinum diamine Chemical class 0.000 title claims description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 16
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 14
- 201000011510 cancer Diseases 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 3
- 229910052799 carbon Inorganic materials 0.000 claims abstract 2
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims description 13
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical group OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N nitrate group Chemical group [N+](=O)([O-])[O-] NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 150000004985 diamines Chemical class 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 229940045985 antineoplastic platinum compound Drugs 0.000 abstract description 2
- 150000003058 platinum compounds Chemical class 0.000 abstract description 2
- DDRVFRXYTKAZHH-UHFFFAOYSA-N 2-carboxyoxycarbonylbenzoic acid Chemical group OC(=O)OC(=O)C1=CC=CC=C1C(O)=O DDRVFRXYTKAZHH-UHFFFAOYSA-N 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical group OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 abstract 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical group OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 abstract 1
- CCQPAEQGAVNNIA-UHFFFAOYSA-N cyclobutane-1,1-dicarboxylic acid Chemical group OC(=O)C1(C(O)=O)CCC1 CCQPAEQGAVNNIA-UHFFFAOYSA-N 0.000 abstract 1
- UKFXDFUAPNAMPJ-UHFFFAOYSA-N ethylmalonic acid Chemical group CCC(C(O)=O)C(O)=O UKFXDFUAPNAMPJ-UHFFFAOYSA-N 0.000 abstract 1
- ROBFUDYVXSDBQM-UHFFFAOYSA-N hydroxymalonic acid Chemical group OC(=O)C(O)C(O)=O ROBFUDYVXSDBQM-UHFFFAOYSA-N 0.000 abstract 1
- 159000000000 sodium salts Chemical class 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 231100000417 nephrotoxicity Toxicity 0.000 description 8
- 210000003734 kidney Anatomy 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 3
- 208000003747 lymphoid leukemia Diseases 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- AYTGUZPQPXGYFS-UHFFFAOYSA-N urea nitrate Chemical compound NC(N)=O.O[N+]([O-])=O AYTGUZPQPXGYFS-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 229910021607 Silver chloride Inorganic materials 0.000 description 2
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 150000003057 platinum Chemical class 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 1
- 201000008228 Ependymoblastoma Diseases 0.000 description 1
- 206010014968 Ependymoma malignant Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 101150052863 THY1 gene Proteins 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 description 1
- 208000029340 primitive neuroectodermal tumor Diseases 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000012956 testing procedure Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 230000001256 tonic effect 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
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/28—Compounds containing heavy metals
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
This invention relates to novel platinum compounds, a method for the preparation thereof, a pharmaceutical composition using the novel compounds and a method for the treatment of cancer using the pharmaceutical composition, wherein the platinum-(II)-diamine complexes are characterized by the formula <IMAGE> wherein R1 and R2 are both ethyl or together with the carbon atom, to which they are bonded, a cyclohexyl group, R3 and R4 are both a hydrogen atom and X is a malonate group, an ethylmalonate group, a hydroxymalonate group, a carboxyphthalate group, a bischloro acetate group, a cyclobutane-1,1-dicarboxylate group, a dinitrate group or an oxalate group or a sodium salt of these groups.
[GB2128615A]
Description
b 6 I '4 4 % The invention relates to novel platinum-diamine complexes, and to a pharmaceutical composition using such a platinum-diamine complex Tor the treatment of cancer, for example, malignant swellings and malignant tumors, as well 5 as to a shaped composition obtained by using this process- Such platinum-diamine complexes are known from the article by A.P. Zipp and S.G. Zipp, J.Chem.Ed., 54 (12), (1977), page 739, tsrhich describes the application of cis-platinum diamine dichloride (POD) for the treatment of cancer* 10 It is mentioned that the platinum compounds have a broad spectrum of activity as antitumor agentsp but also that they have serious drawbacks, in particular that they are toxic to the kidneys. As method for counteracting the kidney toxicity a cis-platinum diamine dichloride is often 15 used in combination with another substance or administered with large quantities of liquid or other techniques are used to bring about an adequate flovi-through of the kidneys. A number of other platinum amine complexes are known including compounds having the formula 2 of the formula 2Q sheet.
Wadley Medical Bulletin, l/ol. 7, No. 1, pp. 114-134, discloses a large number of platinum diamine complexes, including cis-platinum diamine dichloride, for the treatment of cancer. Here, too, the kidney toxicity is stated as the 25 most important drawback of these compounds.
Chem. and Eng. News, 6th, June 1977, pp. 29-30, also describes cis-platinum diamine chloride and its application for the treatment of cancer. Kidney toxicity is also mentioned as the most important drawback of these compounds. 2s In an article in Cancer Chemotherapy Reports Part 1, Vol. 59, No. 3, Nay/June 1975, pp. 629-641, the kidney toxicity of cis-platinum-II-diamine dichloride is also reported. Because of the tonicity of PDD to the kidney 5 and its low therapeutic index, other platinum complexes for the treatment of cancer have been sought. For this-purpose combinations of cis-platinum diamine-II-dichloride with other chemotherapeutic agents were tested; novel platinum complexes were also tried, but they were found 10 to be toxic. It was found, for instance, that although cis-di'chloro-biscvclopentyl amine platinum(II) is only slightly toxic to the kidneys, it is toxic to the spleen. So-called "platinum blues"s a mixture of different amounts of five or more inseparable components have also been dis-15 closed for the treatment of cancer.
Dutch Patent Applications 73,04880; 73,04881; 73,04882 and 77,03752 disclose a large number of platinum diamine complexes, including the compound having formula 2 of the formula sheet. In all of thsse compounds with e nucleus, 20 nitrogen atoms are linked directly to the nucleus. The compounds of the first three Dutch applications were compared with cis-platinum diamine dichloride and were found to have better effects. None of the patent applications states anything about kidney toxicity. 25 jn Dutch Patent Application 79,04740 platinum diamine complexes are describedg which are characterized by the formula 1 of the formula sheet, wherein Rj and Rj are independently of each other a hydrogen atom or a substituted or unsubstituted alkyl, cycloalkyl, aryl or aralkyl group/ 30 while R^ and Rg may be together a substituted or unsubsti-tuted cycloalkyl group, Rj and R& independently of each other are a hydrogen atom or a substituted or unsubstituted alkyl, aryl or aralkyl group, and X is an anionic group.
Now novel platinum diamine complexes have been found, 35 which have the formula 1 of the formula sheet, wherein Rj and R? are both an ethyl group or together with the 0 carton atom, to which thsy ?re bonded, a cyclohexyl group, R3 and are both a hydrogen atom and both groups X are the same and are. each a nitrate group or a chloroacetate group.
The invention further relates to a process for the 5 preparation in a way known per se of these compounds, to a process for the preparation of a medical composition, wherein these compounds are used as active substance, as well as to the so-obtained shaped medical composition.
An extensive research program carried out by the 10 National Cancer Institute, Bethesda, U.S.A., and the European Organization for Research on the Treatment of Cancer, Brussels, Belgium, has shoum that the compounds according to this invention display a high therapeutic activity against cancer in contradiction to the platinum 15 complexes known up to now and used in practice for the combat of cancer, like the cis-platinum diamine dichloride (POD), therein it el so appeared that the compounds according to the invention shot# little or none kidney toxicity.
As it appears from the therapeutical activity values, 20 mentioned in table A, the novel compounds show an important anti-tumor activity against a large number, of different types of tumors, 3uch as P3BB lymphocytic leukemia (PS), 1-1210 lymphoid leukemia (IE), ependymoblastoma and B16 melanocarcinoma (81). The therapeutical activity of the 25 relative novel compounds is higher than that of the cis-platinum diamine dichloride (PDD) which is us?»d as experimental clinical chemotherapeuticum.
A very serious drawback of the PDD used in practice, as oell of ell other plaiinu£»-lI-cotiiplexes with anti-cancer 30 activity and known up to now (with the exception of those, which are described in the Dutch Patent Application 79,04740) is es a 1 reedy mentioned the high tonicity of these compounds, s oT which the kidney toxicity is the most dangerous and in fact limiting for the dose, which can be used in practice.
Surprisingly the compounds according to the invention do not show detrimental side effects on the kidneys. This 5 was demonstrated by means of histological research of rats alter treatment of tonic doses of the compounds described herein be low, while in a similar research with POD serious kidney damages were found.
The new complexes also have no prejudicial influence on 10 the activity of the kidneys. A generally recognized, significant method for the determination of kidney toxicity relates to the evaluation of the percentage urea nitrogen in the blood (blood urea nitrogen, BUN)e also indicated as non-protein nitrogen (non protein nitrogen, NPN). IS It further appears that the compounds according to the invention have no single influence on the urea-nitrogen contents in the blood. As well for doses corresponding raith the LD^q amount as with the LDjQ amount the urea-nitrogen contents in the blood are identical to the control 20 values. The compound PDD, on the contrary, gives at a LD1Q dose after the indicated times already a four times increase of the urea-nitrogen contents, while this at a LDjg dose is increased with a factor of not less than 11. s Table fl finti-cencerous activity An wiceB dose/injection rag/kg T/C (K) 5 formula -4 BDT 1 LE 5,00 207 formula 5 BOF 1 8 229 a: Ho re detailed information concerning the testing procedure and interpretation, victe Instruction 16, Screening data sununary interpretation artd outline of current screen, Maryland, 2001A, 1977. 10 b: 02 - liiouss code B^D^F^ (BOF,); 03 s ftouse code C 57 BL/6; 06 = raouss code CD,F, (COF^). c: PS = P 388 lymphocytic leulamia; LE s L 1210 Lymphoid leukemia; EM - epgndymoblasioma; Bj s 8,^ (?alano~carcinoma. d: Period of survival is the ratio of survival tines of the treated mice 15 (T) to untreated mice (C); the therapeutic activity is significant at T/C * 125.
LE/cis-POO means resistant to cis-POD. f The preparation of the above mentioned compounds is illustrated in the following examples.
The compounds were prepared according to the method of S.C. Dhara: Indian J.Cheia. 8„ 193 (1970). 5 Preparation Exanple Cis=d ichloro-1.1-d i (esiinoma thvl) cyclohexane ola tinum( 11) having the formula 3 of the formula sheet.
To s solution of 16 9 E-t^PtCl^ in 160 ml of water a solution of 26.6 g KI in 20 ml of siater were added and the 10 mixture »es heated for 5 min. in e mater bath.
Hereupon £.6 g 191-di(aminoraethy1) cyclohexane mere added and after the mixture had been stirred for 5 uiinutes, the precipitate «as sucked and urashed three times with hot water, twice with cold ethyl alcohol and twice with ether. j5 11.0 9 of this formed diiodo derivative ware added to a solution of 6.6 g AgNOj in 68 ml water.
Aftarr the mixture had been stirred for 10 minutes at 95-lQ0°Ci, the Ag* was filtered off and washed with «ater. To the clear filtrete 3„28 g KC1 were added and the mixture 20 was stirred for 12 snin. at 95-100°C. After the mixture had been cooled, the precipitate was sucked end washed with water.
Yield: 6.0 g.
Analysis (percentage by veight): 25 Calculated: C: 23.53; H: 6.65; f*l; 6.87; PT: 67.80 found: 23.32; 6.66; 6.66; 67.63.
Example I Cis-l.l-ditaminomethvl)-cyclohe Kane-bis(chloro scetate)-platinum(II), having the formula 4. 1.6 9 of the dichloro derivative prepared according to the Preparation Example (formula 3), were added to a solution of 1.28 g A^N03 in 25 ml of water.
After stirring the mixture during 1 hour at &0°C the AgCl aas filtered off and cashed with water.
To the clear filtrate a solution of 0.73 g monochloro acetic acid end 0,45 g KOH in 25 ml water was added and the mixture was stirred during 2 hours at room temperature. The precipitate was sucked off and washed with stater.
Vield: 1.3 g (65 weight «).
Analysis (weight %): Calculated: C: 27.49; H: 4.23; H: 5.34; found: 27.63; 4.21} 5.55. © 10 15 Example 2 Cis-l.l-bis(emi none thvl )cvcloheaane pla t ir>ue>( 1 S )ni t ra ta „ having the formula 5. & 9 cis-dichloro-1» l-bis(aiainoBe thy 1 )cye.l.ohesene platinum (31) (0.0097 mole) weye suspended in 30 ml distilled water.
To this 3.1 g AgWOj (0.0182 mole) were added and subsequently the mixture mas heated during 1 hour at 40°C while light was excluded.
The formed silverchloride sss filtered off end cashed with distilled water (10 ml).
The clear filtrate mas evaporated under reduced pressure. Weight solid substance: 4.17 g (93.5 weight %). : explodes at about 240°C; decomposes slowly at temperatures below 240°C. : calcul.: C:20.Q3; H:3.93; N:12.14 found : 20.9 ; 4.1 ; 11.9 .
Helting point Analysis (weight Z) 20 25 H-NHR-spectrura CH, (ring) CH2 (NH2) MH2 satellites '95 ' ""pt- H n DH$0-d, (Varisn T60) with respect to TMS: W ] .37 ppm 2.30 ppm 5.67 ppm 5.20 ppm £.18 ppm 56 HZ <* I ®
Claims (14)
1. A platinum-(II)-diamine complex having the formula 1 of the formula sheet, wherein Rj and are both ethyl or together with 5 the carbon atom to which they are bonded, a cyclohexyl group, Rj and Rfi are both a hydrogen atom and both groups X are identical and are each a nitrate group or a chloroacetate group.
2. A platinum diamine complex according to 10 claim 1 having the formula 4 of the formula sheet.
3. A platinum diamine complex according to claim 1 having the formula 5 of the formula sheet. 15
4. A process for the preparation of a medical composition for the treatment of cancer, which comprises using a platinum-(II)- diamine complex having the formula 1, wherein Rj, > Rj. R^ and X 20 have the meaning mentioned in claim 1.
5. ft process according to claim 4, wherein, as platinum-(II)-diamine complex,the compound having the formula 4 is used.
6. A process according to claim 4, 25 wherein, as platinum-(II)-diamine complex,the compound having the formula S is used.
7. A process soY the preparation of a platinum-(11)-diamine complex as claimed in any one of claims 1 to 3, which comprises preparing a * ( 11 platinura-(Il J-diaaine coapleit having the foraula 1, therein R^, R2» aj» R4 ®nd x haw® the ®®snin8 mentioned in claia 1, in a way known per se.
8. A process according to clais 7, wherein a compound having the formula 4 of the formula sheet is prepared.
9. A process according to claim 7, wherein a compound having the formula 5 of the formula sheet is prepared.
10. k pharmaceutical composition for the treatment of cancer, which comprises a platinum (11) diamine comp3.es as claimed in any one of claims 1 to 3, together with a pharmaceutical^ acceptable diluent or carrier.
11. A process as claimed in claim 7, substantially as hereinbefore described with reference to any one of the Examples.
12. A platinum-(II)-diamine complex according to claim 1, substantially as hereinbefore described with particular reference to the accompanying Examples
13. A platinum-(II)-diamine complex according to claim 1, whenever prepared by a process claimed in any one of claims 7-9 or claim 11.
14. A pharmaceutical composition according to claim 10, substantially as hereinbefore described. F. R. KELLY & CO., AGENTS FOR THE APPLICANTS
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL8204067A NL8204067A (en) | 1982-10-21 | 1982-10-21 | PLATINUM DIAMINE COMPLEXES, METHOD FOR PREPARING THE SAME, METHOD FOR PREPARING A MEDICINAL PRODUCT USING SUCH PLATINADIAMINE COMPLEX FOR THE TREATMENT OF CANCER, PREVENTLY PREVENTED. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE832459L true IE832459L (en) | 1984-04-21 |
| IE56124B1 IE56124B1 (en) | 1991-04-24 |
Family
ID=19840444
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE2459/83A IE56124B1 (en) | 1982-10-21 | 1983-10-20 | Platinum diamine complexes |
Country Status (28)
| Country | Link |
|---|---|
| JP (1) | JPS5993091A (en) |
| KR (1) | KR910002536B1 (en) |
| AT (1) | AT390610B (en) |
| AU (1) | AU562964B2 (en) |
| BE (1) | BE898058A (en) |
| CA (1) | CA1229618A (en) |
| CH (1) | CH658244A5 (en) |
| CS (1) | CS242888B2 (en) |
| DD (1) | DD217522A5 (en) |
| DE (1) | DE3337333A1 (en) |
| DK (2) | DK483083A (en) |
| ES (1) | ES8406498A1 (en) |
| FI (1) | FI76351C (en) |
| FR (1) | FR2534907B1 (en) |
| GB (1) | GB2128615B (en) |
| GR (1) | GR79652B (en) |
| HU (1) | HU188035B (en) |
| IE (1) | IE56124B1 (en) |
| IT (1) | IT1169858B (en) |
| LU (1) | LU85054A1 (en) |
| NL (1) | NL8204067A (en) |
| NO (1) | NO171276C (en) |
| NZ (1) | NZ206018A (en) |
| PH (1) | PH24077A (en) |
| PT (1) | PT77542B (en) |
| SE (1) | SE8305783L (en) |
| YU (1) | YU43554B (en) |
| ZA (1) | ZA837857B (en) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4786725A (en) * | 1982-06-28 | 1988-11-22 | Engelhard Corporation | Solubilized platinum (II) complexes |
| US4758588A (en) * | 1983-06-20 | 1988-07-19 | Research Corporation Technologies | Diaminocyclohexane platinum complexes |
| US4661516A (en) * | 1983-06-20 | 1987-04-28 | Research Corporation | Diaminocyclohexane platinum complexes |
| EP0169645A1 (en) * | 1984-06-27 | 1986-01-29 | Johnson Matthey Public Limited Company | Platinum co-ordination compounds |
| DE3432320A1 (en) * | 1984-09-03 | 1986-03-13 | Behringwerke Ag, 3550 Marburg | CIS-PLATINUM COMPLEXES WITH A PENTAERYTHRITE DERIVATIVE AS A LIGAND, METHOD FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL AGENT CONTAINING THESE COMPOUNDS |
| HU193809B (en) * | 1984-09-12 | 1987-12-28 | Chugai Pharmaceutical Co Ltd | Process for producing new platinum complexes |
| US4737589A (en) * | 1985-08-27 | 1988-04-12 | Nippon Kayaku Kabushiki Kaisha | Platinum Complexes |
| US4880790A (en) * | 1986-01-31 | 1989-11-14 | American Cyanamid Company | (Gem-heterocyclodimethanamine-N,N')platinum complexes |
| US4760157A (en) * | 1986-01-31 | 1988-07-26 | American Cyanamid Company | (2,2,-bis(aminomethyl)-1,3-propanediol-N,N')platinum complexes |
| DE3630497A1 (en) * | 1986-09-08 | 1988-03-10 | Behringwerke Ag | CIS-PLATINUM COMPLEXES, METHOD FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL AGENTS CONTAINING THESE COMPOUNDS |
| ATE53217T1 (en) * | 1986-10-03 | 1990-06-15 | Asta Pharma Ag | DIAMININE-PLATINUM (II) COMPLEX COMPOUNDS WITH A HYDROXYLATED 2-PHENYL-INDOLE RING. |
| JPS63203692A (en) * | 1987-02-19 | 1988-08-23 | Nippon Kayaku Co Ltd | Novel platinum complex |
| AT390065B (en) * | 1987-10-08 | 1990-03-12 | Behringwerke Ag | cis-Platinum complexes, process for their preparation and pharmaceutical compositions containing these compounds |
| NL8802150A (en) * | 1988-08-31 | 1990-03-16 | Tno | PLATINUM (II) DIAMINE COMPLEX, PROCESS FOR PREPARING THIS COMPOUND, PREPARATION WITH ANTI-TUMOR EFFECT, CONTAINING THIS COMPOUND AND FORMED PREPARATIONS WITH ANTI-TUMOR EFFECT. |
| NL8802149A (en) * | 1988-08-31 | 1990-03-16 | Tno | PLATINUM (IV) DIAMINE COMPLEX, METHOD FOR PREPARING THIS COMPOUND, PREPARATION WITH ANTI-TUMOR EFFECT, CONTAINING AT LEAST A PLATINUM COMPOUND, AND FORMED PREPARATIONS WITH ANTI-TUMOR EFFECT. |
| CN102924528B (en) * | 2012-10-29 | 2015-04-15 | 东南大学 | Anti-tumor bivalent platinum complex and preparation method for complex and ligand of complex |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4115418A (en) * | 1976-09-02 | 1978-09-19 | Government Of The United States Of America | 1,2-diaminocyclohexane platinum (ii) complexes having antineoplastic activity |
| US4206226A (en) * | 1977-08-29 | 1980-06-03 | The United States Of America As Represented By The Department Of Health, Education And Welfare | Use of 4-carboxy-phthalato-(1,2-diaminocyclohexane)-platinum(II) and alkali metal salts thereof in alleviating L1210 murine leukemia |
| NL189358C (en) * | 1978-07-06 | 1993-03-16 | Tno | PROCESS FOR PREPARING A MEDICINE FOR THE TREATMENT OF CANCER, AND AN PLATINUM-DIAMMINE COMPLEX DERIVED FROM A 1,3-ALKANE DIAMINE. |
| NL7807334A (en) * | 1978-07-06 | 1980-01-08 | Tno | PLATINUM DIAMINE COMPLEXES, METHOD FOR PREPARING THE SAME, METHOD FOR PREPARING A MEDICINAL PRODUCT USING SUCH A PLATINUM DIAMOND COMPLEX FOR THE TREATMENT OF CANCER, SO PREVENTLY DRIVED. |
| AU538863B2 (en) * | 1980-05-27 | 1984-08-30 | Bristol-Myers Company | Platinum complex salts have anti-tumor property |
| US4322362A (en) * | 1980-07-28 | 1982-03-30 | Bristol-Myers Company | Salts of 2-hydroxymalonate platinum complexes |
-
1982
- 1982-10-21 NL NL8204067A patent/NL8204067A/en not_active Application Discontinuation
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1983
- 1983-10-13 DE DE19833337333 patent/DE3337333A1/en not_active Ceased
- 1983-10-18 AU AU20275/83A patent/AU562964B2/en not_active Ceased
- 1983-10-19 IT IT23359/83A patent/IT1169858B/en active
- 1983-10-19 CA CA000439308A patent/CA1229618A/en not_active Expired
- 1983-10-20 YU YU2107/83A patent/YU43554B/en unknown
- 1983-10-20 DK DK483083A patent/DK483083A/en not_active Application Discontinuation
- 1983-10-20 FR FR8316715A patent/FR2534907B1/en not_active Expired
- 1983-10-20 FI FI833842A patent/FI76351C/en not_active IP Right Cessation
- 1983-10-20 GB GB08328084A patent/GB2128615B/en not_active Expired
- 1983-10-20 DD DD83255826A patent/DD217522A5/en not_active IP Right Cessation
- 1983-10-20 GR GR72754A patent/GR79652B/el unknown
- 1983-10-20 PT PT77542A patent/PT77542B/en unknown
- 1983-10-20 IE IE2459/83A patent/IE56124B1/en not_active IP Right Cessation
- 1983-10-20 LU LU85054A patent/LU85054A1/xx unknown
- 1983-10-20 SE SE8305783A patent/SE8305783L/en not_active Application Discontinuation
- 1983-10-20 NZ NZ206018A patent/NZ206018A/en unknown
- 1983-10-20 CH CH5718/83A patent/CH658244A5/en not_active IP Right Cessation
- 1983-10-20 AT AT0373083A patent/AT390610B/en not_active IP Right Cessation
- 1983-10-20 HU HU833623A patent/HU188035B/en not_active IP Right Cessation
- 1983-10-20 NO NO833825A patent/NO171276C/en unknown
- 1983-10-21 JP JP58196286A patent/JPS5993091A/en active Granted
- 1983-10-21 ES ES526670A patent/ES8406498A1/en not_active Expired
- 1983-10-21 ZA ZA837857A patent/ZA837857B/en unknown
- 1983-10-21 BE BE0/211755A patent/BE898058A/en not_active IP Right Cessation
- 1983-10-21 KR KR1019830004987A patent/KR910002536B1/en not_active Expired
- 1983-10-21 PH PH29726A patent/PH24077A/en unknown
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1992
- 1992-06-09 DK DK075592A patent/DK75592A/en not_active Application Discontinuation
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| MM4A | Patent lapsed |