Title: Platinum-diamine complexes, a method for the preparation of a medicine using such a platinum-diamine complex for the treatment of malignant tumor in mice

We claim:

1. Platinum-diamine complexes having the formula: ##STR20## wherein R₁ and R₂ independently of each other may be selected from the group consisting of hydrogen, an alkyl group having 1-20 carbon atoms, a cycloalkyl group having from 3-7 carbon atoms in the ring, an aralkyl group, and an aryl group having 1-20 carbon atoms, whereas R₁ and R₂ together may form a cycloalkyl group having 3-7 carbon atoms in the ring and having the formula: ##STR21## wherein n is 2 to 7 and wherein R₃ and R₄ independently of each other are selected from the group consisting of hydrogen, an alkyl group having 1-20 carbon atoms, an aryl group or an aralkyl group having 1-20 carbon atoms in the alkyl group and X is an anionic group, providing that when X is either chlorine or malonato, R₁, R₂, R₃ and R₄ are not each H; when X is chlorine and R₁ and R₂ are each H, R₃ and R₄ are not each methyl; when X is chlorine and R₁ and R₂ are each methyl; R₃ and R₄ are not each H, and when X is chlorine R₁ is hydrogen and R₂ is methyl, R₃ and R₄ are not each hydrogen.

2. Platinum-diamine complexes having the formula: ##STR22## wherein R₃ and R₄ independently of each other are selected from the group consisting of hydrogen, alkyl group having 1-20 carbon atoms, an aryl group or an aralkyl group having 1-20 carbon atoms in the alkyl group and X is an anionic group, selected from the group consisting of chlorine, bromine, iodine, sulphate, phthalate, acetate, oxalate, malonate, substituted malonate, carboxylate, and isocitrate.

3. Cis-dichloro-1,1-di(aminomethyl)cycloalkyl platinum(II) having the formula: ##STR23## wherein n is 3 to 7.

4. Cis-diiodo-1,1-di(aminomethyl)cyclohexane platinum(II) having the formula: ##STR24##.

5. Cis-cyclopentamethylene malonato-1,1-di(aminomethyl)cyclohexane platinum(II) having the formula: ##STR25##.

6. Cis-dichloro-(2-methyl-2-ethyl)-1,3-propane diamine platinum(II) having the formula: ##STR26##.

7. Cis-dichloro-2,2-diethyl-1,3-propane diamine platinum(II) having the formula: ##STR27##.

8. Cis-dichloro-1,1-di(aminomethyl)cyclopentane platinum(II) having the formula: ##STR28##.

9. Cis-1,1-di(aminomethyl)cyclohexane platinum(II) sulphate having the formula: ##STR29##.

10. Cis-dichloro-1,1-di(aminomethyl)cyclobutane platinum(II) having the formula: ##STR30##.

11. Cis-dichloro-2,2-dibenzyl-1,3-propane diamine platinum(II) having the formula: ##STR31##.

12. Cis-dichloro-2,2-diisopropyl-1,3-propane diamine platinum(II) having the formula: ##STR32##.

13. Cis-4-carboxyphtalato-1,1-di(aminomethyl)cyclohexane platinum(II) having the formula: ##STR33##.

14. Cis-1,1-di(aminomethyl)-cyclohexane-bis(chloroacetato) platinum(II) having the formula: ##STR34##.

15. Cis-2,2-diethyl-1,3-propanediamine platinum(II) sulphate having the formula: ##STR35##.

16. Cis-1,1-di(aminomethyl)cyclohexanemalonato platinum(II) having the formula: ##STR36##.

17. Cis-1,1-di(aminomethyl)cyclohexanehydroxymalonato platinum(II) having the formula: ##STR37##.

18. Cis-2,2-diethyl-1,3-diaminopropane 2-ethylmalonato platinum(II) having the formula: ##STR38##.

19. Cis-2,2-diethyl-1,3-diaminopropane 2-hydroxymalonato platinum(II) having the formula: ##STR39##.

20. Cis-1,1-di(aminomethyl)cyclhexane 2-ethylmalonato platinum(II) having the formula: ##STR40##.

21. Cis-2,2-diethyl-1,3-diaminopropane 2-hydroxymalonato platinum(II) sodium salt, having the formula: ##STR41##.

22. Cis-1,1-di(aminomethyl)cyclohexane 1,1-cyclobutanedicarboxylato platinum(II) having the formula: ##STR42##.

23. Cis-2,2-diethyl-1,3-diaminopropane 1,1-cyclobutanedicarboxylato platinum(II) having the formula: ##STR43##.

24. Cis-1,1-di(aminomethyl)cyclohexane platinum(II) isocitrate having the formula: ##STR44##.

25. Cis-dichloro-1,1-di(aminomethyl)cyclohexane platinum(II) having the formula: ##STR45##.

26. A pharmaceutical composition comprising a liquid or solid carrier and an amount of at least one of the compounds described in claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 sufficient to treat malignant tumors in mice.

27. A method of treating malignant tumors in mice which consists of administering a therapuetically effective amount of the composition described in claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 to mice having malignant tumors.

28. A pharmaceutical composition comprising a liquid or solid carrier and an amount sufficient to treat malignant tumors in mice of at least one of a platinum diamine complex having the formula: ##STR46## wherein R₁ and R₂ independently of each other may be selected from the group consisting of hydrogen, an alkyl group having 1-20 carbon atoms, a cycloalkyl group having from 3-7 carbon atoms in the ring, an aralkyl group and an aryl group having 1-20 carbon atoms, whereas R₁ and R₂ together may form a cycloalkyl group having 3-7 carbon atoms in the ring and having the formula: ##STR47## wherein n is 2 to 7 and wherein R₃ and R₄ independently of each other are selected from the group consisting of hydrogen, an alkyl group having 1-20 carbon atoms, an aryl group or an aralkyl group having 1-20 carbon atoms in the alkyl group and X is an anionic group.

29. A method of treating malignant tumors in mice which consists of administering a therapeutically effective amount of the composition described in claim 28 to mice having malignant tumors.


Other info:


Inventors: Berg, Jan (Nieuwegein, NL)
Verbeek, Francois (Harmelen, NL)
Bluten, Eric J. (Blaricum, NL)

Application Number: 06/287531
Filing Date: 1981-07-27
Publication_date: 1983-10-18
Assignee: Tno (NL)

Primary Class(es): 514/492 556/137, 556/40, 987/11
Other Classes: C07F15/00; A61K31/28; C07F15/00
US Patent Ref:

3892790	July, 1975	Tobe et al.	260/429R	Compositions containing platinum
3904663	September, 1975	Tobe et al.	260/429R	Compositions containing platinum
4140707	February, 1979	Cleare et al.	260/429R	Malonato platinum anti-tumor compounds

Other Refs: Other References: Appleton, T. G.; Hall, J. R., Inorganic Chemistry, vol. 11, No. 1, p. 112, 1972.
Appleton, T. G., Hall, J. R., Inorganic Chemistry, vol. 9, No. 8, p. 1800, 1970.
Chemical Abstracts, vol. 80, p. 4, ref. 66593d.
Chemical Abstracts, vol. 87, 1977, p. 11, ref. 15694z.
Chemical Abstracts, vol. 87, ref. 145547q, p. 14.
Chemical Abstracts, vol. 78, 1973, p. 10, ref. 105899p.
Bioinorg. Chem. 2, 187-210, (1973).
Platinum Metal Reviews 17, 2-13, (1973).
Cleare, M. J. and Hoeschele, J. D., Platinum Metals Rev. 17, (1), 1973.

Primary Examiner: Sneed, Helen M. S.
Assistant Examiner:
Attorney: Brumbaugh, Graves, Donohue & Raymond