Title: Platinum(IV)-diamine complexes, a process for the preparation thereof, a process for the preparation of a medicine using such a platinum(IV)-diamine complex for the treatment of malignant tumors in mice

We claim:

1. Platinum(IV)-diamine complexes having the formula: ##STR8## wherein R₁ and R₂ are independently from each other a hydrogen atom or an alkyl, aryl or aralkyl group having 1-20 carbon atoms or a cycloalkyl group having 3-7 carbon atoms, while R₁ and R₂ together may be a cycloalkyl group having 3-7 carbon atoms, R₃ and R₄ are independently from each other a hydrogen atom or alkyl, aryl, aralkyl group having 1-20 carbon atoms and X and Y are independently from each other an anionic group, provided that when X and Y are both chlorine or when X is chlorine and Y is hydroxy R₁, R₂, R₃ and R₄ are not each hydrogen; when X and Y are both chlorine and R₁ and R₂ are both hydrogen, R₃ and R₄ are not each methyl and when X and Y are both chlorine and R₁ and R₂ are both methyl R₃ and R₄ are not each hydrogen.

2. The platinum(IV)-diamine complex as described in claim 1 wherein R₃ and R₄ are both hydrogen.

3. Cis-dichloro-trans-dihydroxy-1,1-bis (aminomethyl) cyclohexane platinum(IV) having the formula: ##STR9##.

4. Cis-tetrachloro-1,1-bis(aminomethyl) cyclohexane platinum(IV) having the formula: ##STR10##.

5. Cis-tetrachloro-2,2-diethyl-1,3-diaminopropane platinum(IV) having the formula: ##STR11##.

6. Cis-tetrachloro-1,1-bis(aminomethyl) cyclobutane platinum(IV) having the formula: ##STR12##.

7. Cis-dichloro-trans-dihydroxy-2,2-diethyl-1,3-diamonopropane platinum(IV) having the formula: ##STR13##.

8. Cis-tetrachloro-1,1-bis(aminomethyl) cyclopentane platinum(IV) having the formula: ##STR14##.

9. Cis-dichloro-trans-dihydroxy-1,1-bis (aminomethyl) cyclopentane platinum(IV) having the formula: ##STR15##.

10. Pharmaceutical composition comprising a suitable carrier and an amount sufficient to treat malignant tumors in mice of at least one of the platinum(IV) diamine complexes having the formula: ##STR16## wherein R₁ and R₂ are independently from each other a hydrogen atom or an alkyl, cycloalkyl, aryl or aralkyl group, while R₁ and R₂ together may be a cycloalkyl group, R₃ and R₄ are independently from each other a hydrogen atom or alkyl, aryl, aralkyl group and X and Y are independently from each other an anionic group, provided that when X and Y are both chlorine and R₁ and R₂ are both methyl, R₃ and R₄ are not each hydrogen.

11. A pharmaceutical composition comprising a suitable carrier and an amount of the compound described in claim 3 sufficient to treat malignant tumors in mice.

12. A pharmaceutical composition comprising a suitable carrier and an amount of the compound described in claim 4 sufficient to treat malignant tumors in mice.

13. A pharmaceutical composition comprising a suitable carrier and an amount of the compound described in claim 5 sufficient to treat malignant tumors in mice.

14. A pharmaceutical composition comprising a suitable carrier and an amount of the compound described in claim 6 sufficient to treat malignant tumors in mice.

15. A pharmaceutical composition comprising a suitable carrier and an amount of the compound described in claim 7 sufficient to treat malignant tumors in mice.

16. A pharmaceutical composition comprising a suitable carrier and an amount of the compound described in claim 8 sufficient to treat malignant tumors in mice.

17. A pharmaceutical composition comprising a suitable carrier and an amount of the compound described in claim 9 sufficient to treat malignant tumors in mice.

18. A method for treating malignant tumors in mice which consists of administering a therapeutically effective amount of the composition as described in claim 1, 2, 3, 4, 5, 6, 7, 8 or 9 to mice having malignant tumors.

19. A method of treating malignant tumors in mice which consists of administering a therapeutically effective amount of the composition as described in claim 10.


Other info:


Inventors: Bulten, Eric J. (Bilthoven, NL)
Verbeek, Francois (Harmelen, NL)

Application Number: 06/232298
Filing Date: 1981-02-06
Publication_date: 1984-02-14
Assignee: Tno (NL)

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

4053587	October, 1977	Davidson et al.	424/131	Method of treating viral infections
4119654	October, 1978	Tobe et al.	260/429R	Compositions containing platinum
4140707	February, 1979	Cleare et al.	260/429R	Malonato platinum anti-tumor compounds
4228090	October, 1980	Hydes et al.	260/429R	Compositions containing platinum
4250189	February, 1981	Hydes et al.	260/429R	Compositions containing platinum

Other Refs: Other References: Braddock et al., Chemico-Biological Interactions, vol. 11, No. 3, pp. 158-159 (1975).
Van Kralingen, C. G., Antitumor Platinum Compounds; Synthesis, Structure and Biological Activity, No. 7, 1979.
B. Rosenberg and L. Van Camp, Cancer Research 30 (1970) 1799-1802.
A. P. Zipp and S. G. Zipp, J. Chem. Ed., 54 (12) (1977) p. 739.
M. L. Tobe and A. R. Khokhar, J. Clinical Hematol. Oncol., 7 (1) (1977), pp. 114-134.
Appleton, T. C. and Hall, J. R., Inorganic Chemistry, vol. 11, No. 1, 1972, pp. 112-117.

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