(N-PHOSPHONOACETYL-L-ASPARTATO) (1,2 DIAMINOCYCLOHEXANE) PLATINUM (II) AND THE SODIUM, POTASSIUM OR LITHIUM SALTS THEREOF, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

摘要

where X is Na<+>, K<+>, Li<+> or H.
(N-phosphonacetyl-L-aspartato) (1,2-diaminocyclohexane)platinum(II) or alkali metal salt thereof has shown antitumor activity in animals such as activity against murine leukemia L1210. Additionally, this agent is used against B-16 and Colon 38 tumors and also Ehrlich ascites tumor. It is effective in dosages of 5-60 mg/kg of body weight and is potentiated in a treatment with cyclophosphamide (CY) (50 mg/kg of body weight) to which may be added hydroxyurea (HU) (1,000-1,500 mg/kg of body weight).
In binary treatment with cis-dichlorodiamineplatinum(II) (or cisplatin) the preferred ratio of the present compound to cisplatin is about 10:1 with a range of about 10:1 to 1 : 10 in mg/kg of body weight.
As to the variations in the formula on the left hand side of the formula, it may be varied as monodentate, such as cisplatin containing a single amine group proceeding from the ring, or bidentate, such as the present compound. The saturated cyclo ring may be C4 or C5-C7 in addition to the present cyclohexane.
The present platinum compound may be prepared by reacting the known L-aspartic acid, N-(phosphonacetyl-) disodium salt (PALA; NSC-224 131), with dinitrato(1,2-diaminocyclohexane)platinum(II) (NSC-239 851). This compound N-phosphonacetyl-L-aspartato (1,2-diaminocyclohexane)platinum(II) may be combined in multiple drug regimen with substantially improved yield cures over the parent compounds. For example, the compound denoted Pt-268 may be combined in a dual regimen with cyclophosphamide (CY), hydroxyurea (HU), and cisplatin.