Compositions containing platinum

A cis co-ordination compound of platinum having the structure ##STR1## in which X and Y are the same or different ligands selected from halide, sulphate, phosphate, nitrate, carboxylate, carboxylate substituted with halogen and water and A and B are the same or different straight-chain alkyl amines containing at least 3 carbon atoms in the alkyl chain co-ordinated to the Pt through their N atoms, such that the platinum is present as Pt.sup.2+.

This invention relates to new platinum co-ordination compounds and to 
pharmaceutical compositions containing them. 
According to a first aspect of the present invention, a composition of 
matter comprises a cis co-ordination compound of platinum having the 
structure 
##STR2## 
in which X and Y are the same or different ligands selected from halide, 
sulphate, phosphate, nitrate, carboxylate, substituted carboxylate and 
water and A and B are the same or different straight-chain amines 
co-ordinated to the Pt through their N atoms, such that the platinum is 
present as Pt.sup.2. By phosphate we mean both H.sub.2 PO.sub.4 --and 
HPO.sub.4.sup.2-. 
Where X and/or Y is represented by carboxylate or substituted carboxylate, 
the general formula of which is C.sub.n R.sub.2n+1 CO.sub.2 H, that n is 
an integer from 1 to 9 inclusive and that the B groups are the same or 
different and are selected from hydrogen, substituted or unsubstituted 
straight- or branched-chain alkyl, arly, alkaryl, aralkyl, alkenyl, 
cycloalkyl and cycloalkenyl, halogen, pseudohalogen, hydroxy, carbonyl, 
formyl, nitro, amido, amino, alkoxy, aryloxy and sulphonic acid salts. We 
intend the above definition also to include oxygen and sulphur, such that 
one doubly-bonded oxygen or sulphur atom is represented by two R groups. 
Where X and Y are both carboxylate, they can together comprise a 
discarboxylate bidentate ligand, for example oxalate and ligands having 
the general formula 
EQU -OOC.sub.-- (CR.sub.y.sup.1 R.sub.z.sup.2).sub.n.spsb.1 --COO.sup.- 
where n.sup.1 is an integer from 2 to 6, R.sup.1 and R.sup.2 are the same 
or different and are selected from H, lower alkyl, aryl, alkaryl, aralkyl, 
alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, halogen, 
pseudohalogen, OH, or are combined with the carbon atoms to form a 
cycloalkyl or an aryl group, and substituted derivatives thereof, and y 
and z are either 0 or 1 as long as (y+z) is equal to 1 or 2. 
Suitable dicarboxylate ligands are the succinato, glutarato 
(pentanedioato), adipato (hexanedioato), pimelato (heptanedioate) malaro 
(cis-butenedioato) and phthalato (o-benzenedicarboxylate) ligands and 
these may be either substituted or unsubstituted. 
The ligands may contain substituents selected from the group consisting of 
lower alkyl, (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl); aryl 
(e.g. phenyl, lower alkyl-, lower alkenyl-, halo-, nitro-, lower 
alkoxy-substituted phenyl and naphthyl) aralkyl, (e.g. 
phenymethyl(benzyl), 2-(1-naphthyl) methyl); alkenyl, (e.g. 
4-amino-1-butene, allyl); cyclo-alkyl, (e.g. cyclopropyl, cyclohexyl); 
cyclo-alkenyl, (e.g. 2-cyclopenten-1-yl), 2-cyclo-hexen-1-yl); alkoxy; 
(e.g. methoxy, ethoxy), and hydroxy. 
The straight chain amine has the general formula: 
EQU n--C.sub.x R.sup.3.sub.2x+1 NH.sub.2. 
in which x is an integer from 1 to 9 inclusive and the R.sup.3 groups are 
the same or different and are selected from hydrogen, aryl, cycloalkyl and 
cycloalkenyl, aralkyl, halogen, pseudohalogen (as hereinafter defined), 
hydroxy, alkoxy, aryloxy, carbonyl, formyl, nitro, amido, amino, 
acylamino, sulphonic acid, sulphonic acid salt, carboxylic acid ester and 
carboxylic acid salt. Even more preferably all the R.sup.3 groups are 
hydrogen. However, where one or more of the R.sup.3 groups is other than 
hydrogen, it can be a solubilising group, for example a sulphonic acid, 
carboxylic acid, carboxylic acid salt or a sulphonic acid salt. Where a 
solubilising group is used in the form of a salt, the salt can be, for 
example, the sodium, potassium or lithium salt, where conditions are 
appropriate and the clinical conditions require high solubility. We intend 
the above definition of R.sup.3 also to include oxygen and sulphur, such 
that one doubly-bonded oxygen or sulphur atom is represented by two 
R.sup.3 groups. 
The term "pseudohalogen" in this specification has the meaning given on p. 
560 of "Advanced Inorganic Chemistry" by Cotton and Wilkinson, 
Interscience Publishers, 1966, as being "a molecule consisting of more 
than two electronegative atoms which, in the free state, resembles the 
halogens; these pseudohalogens give rise to anions which resemble the 
halide ions in behaviour". Examples of suitable pseudohalogenides are 
cyanide, cyanate, thiocyanate and azide. 
The term "cis" as applied to the compounds of the invention indicates that 
the compounds have planar structure and that A cannot be in a position 
trans to B and that X cannot be in a position trans to Y. 
Two particular compounds according to the invention are cis dichloro 
di-n-propylamine Pt (II) and cis dichloro-di-n-butylamine Pt(II). 
Normally the compound is used in association with a pharmaceutically 
acceptable carrier therefore. Accordingly, in a second aspect, the present 
invention provides a pharmaceutical composition which comprises a compound 
according to the first aspect of the invention and a 
pharmaceutically-acceptable carrier for said compound; these compositions 
can be formulated so as to be suitable, for example, for parenteral or 
oral administration to animals.

PREATION OF COMPLEXES ACCORDING TO THE INVENTION 
The following Examples describe some specific preparations of compounds 
according to the invention. 
Examples 1, 2 and 3 describe the preparation of compounds formed by 
reaction of cis-[PtI.sub.2 A.sub.2 ] with AgNO.sub.3 and throughout the 
remainder of this specification such compounds will be referred to as 
"diaquo compounds". In each case, the cis-[PtI.sub.2 A.sub.2 ] may be 
prepared by the method of S. C. Dhara described in the Indian Journal of 
Chemistry, 8, 143 (1970). 
EXAMPLE 1 
Preparation of the n-butylamine diaquo complex 
cis-[PtI.sub.2 (n-C.sub.4 H.sub.9 NH.sub.2).sub.2 ] (120 g, 0.20 mol) was 
slurried with a warm solution of silver nitrate (66 g, 0.38 mol) in water 
(200 ml). The mixture was stirred for 3 hours during which time the yellow 
suspension turned pale grey. The mixture was then treated with charcoal, 
stirred and filtered through a porosity 4 sinter. The residue was washed 
once with 30 ml of water and the washings were combined with the filtrate 
(total volume 300 ml). The addition of a crystal of sodium chloride gave 
no precipitate of AgCl which indicated that the solution was silver free. 
The solution was treated with charcoal and filtered through a porosity 4 
sinter immediately before use since there was a tendency for the pale 
yellow solution to darken owing to slow decomposition to platinum. 
EXAMPLE 2 
Preparation of the n-propylamine diaquo complex 
Cis-[PtI.sub.2 (n-C.sub.3 H.sub.7 NH.sub.2).sub.2 ] (127 g, 0.22 mol) was 
slurried with a warm (50.degree. C.) solution of silver nitrate (73 g, 
0.43 mol) in 130 mls of water. The mixture was stirred for 4 hours during 
which time the yellow suspension turned dark grey. The mixture was then 
treated with charcoal, stirred and filtered through a porosity 4 sinter. 
The residue was triturated with water (20 mls) and the filtrates combined 
to give a clear orange solution (total volume 150 mls). The addition of a 
crystal of NaCl gave no precipitate of AgCl which indicated that the 
solution was silver-free. The solution was treated with charcoal and 
filtered through a porosity 4 sinter immediately before use as there was a 
tendency for the pale yellow solution to darken owing to slow 
decomposition to platinum. 
EXAMPLE 3 
Preparation of the n-pentylamine diaquo complex 
cis-[PtI.sub.2 (n--C.sub.5 H.sub.11 NH.sub.2).sub.2 ] (86 g, 0.14 mol) was 
slurried with a warm (50.degree. C.) solution of silver nitrate (43.8 g, 
0.27 mol) in 100 mls of water and 80 mls of ethanol. The mixture was 
stirred overnight, and then stirred with charcoal. The solids were 
filtered off on a porosity 4 sinter to give a cloudy orange solution. This 
cloudiness persisted despite several filtrations through porosity 4 
sinters. 
EXAMPLE 4 
Cis-bis(chloroacetato) bis(n-propylamine)platinum II, cis-[PtClCH.sub.2 
CO.sub.2).sub.2 (n-C.sub.3 H.sub.7 NH.sub.2).sub.2 ] 
An aqueous solution of the n-propylamine diaquo complex (37 mls, 0.054 mol) 
was added to a warm, stirred solution of potassium chloroacetate, prepared 
from chloroacetic acid (15 g, 0.16 mol) and potassium hydroxide (9 g, 0.16 
mol) in 100 mls of water. A dark, oily solid formed which changed to a 
more brittle solid on standing (60 hours). The pale yellow brown solid was 
filtered off on a porosity 3 sinter, washed well with water and dried in 
vacuo at 50.degree. C. 
Crude yield=14.3 g (54%). 
The crude produce (14.3 g) was dissolved in 125 mls of boiling ethanol. The 
solution was stirred with charcoal, filtered while hot through a porosity 
4 sinter and allowed to cool. A white crystalline solid was formed. 
Yield=6.4 g (overall yield=24%). 
______________________________________ 
Elemental analysis 
Pt C H N 0 Cl 
______________________________________ 
Calculated % 
39.0 24.0 4.4 5.6 12.8 14.2 
Found % -- 23.8 4.4 5.5 -- -- 
______________________________________ 
EXAMPLE 5 
Cis-bis(bromoacetato)bis(n-propylamine)platinum(II), cis-[Pt(BrCH.sub.2 
CO.sub.2).sub.2 (n-C.sub.3 H.sub.7 NH.sub.2).sub.2 ] 
Bromoacetic acid (5 g, 0.04 mol) was added to an aqueous solution of the 
n-propylamine diaquo complex (26 ml, 0.01 mol). A concentrated aqueous 
solution of sodium hydroxide was then added to the stirred solution until 
the pH had increased to 6-7. This gave an oil which transformed to a solid 
on standing overnight. The solid was then filtered off on a porosity 3 
sinter, washed well with water and dried by suction. 
Crude yield=1.5 g (25%). 
The crude bromoacetato complex was rather inefficiently recrystallized from 
5 ml of hot ethanol, which gave pale yellow crystals. 
Yield=0.1 g (overall yield=2%). 
______________________________________ 
Elemental Analysis 
Pt C H N O Br 
______________________________________ 
Calculated % 
33.1 20.4 3.8 4.8 10.9 27.1 
Found % -- 19.4 3.6 4.8 -- -- 
______________________________________ 
Infra-red Spectrum 
The nitrogen-hydrogen stretching modes (.nu..sub.N--H) occur at 3190, 3150 
and 3110 cm.sup.-1 and there is a bromoacetate absorption at 1615 
cm.sup.-1 (.nu..sub.C.dbd.O). 
EXAMPLE 6 
Cis-bis (n-butylamine) bis(chloroacetato) platinum (II), cis-[Pt(ClCH.sub.2 
CO.sub.2).sub.2 (n-C.sub.4 H.sub.9 NH.sub.2).sub.2 ] 
A solution of potassium chloroacetate in 100 mls of water, prepared from 
chloroacetic acid (21.6 g, 0.14 mol) was added to a solution of the 
n-butylamine diaquo complex in water (76 mls, 0.046 mol). A blue solution 
was formed immediately in which a dark blue-green oil settled. A white 
suspension was also observed. The mixture was allowed to stand for 60 
hours and then the solids were filtered off on a porosity 3 sinter, washed 
well with water and air dried. The solid was then crushed in a mortar, 
washed with diethyl ether and dried in vacuo at 60.degree. C. The crude 
product was pale green. 
Crude yield=11.1 g (42%). 
The crude product (9.6 g) was dissolved in 50-60 mls of hot ethanol. The 
orange solution was stirred with charcoal and filtered while hot through a 
porosity 4 sinter. White acicular crystals formed on cooling the filtrate 
which was subsequently chilled at 5.degree. C. overnight. The crystals 
filtered off on a porosity 3 sinter and washed twice with ethanol, causing 
them to effloresce to a white powder, which was dried in vacuo at 
40.degree. C. 
Yield--3.3 g (overall yield=12.6%). 
______________________________________ 
Elemental Analysis 
Pt C H N 0 Cl 
______________________________________ 
Calculated % 
36.9 27.3 5.0 5.3 12.1 13.4 
Found % -- 26.9 5.0 5.3 -- -- 
______________________________________ 
Infra-red Spectrum 
The nitrogen-hydrogen stretching modes (.nu..sub.N--H) occur at 3195 and 
3130 cm.sup.-1 and there is a chloroacetate absorption at 1650 cm.sup.-1 
(.nu..sub.C.dbd.O). 
EXAMPLE 7 
Aquobis(n-butylamine)sulphatoplatinum(II), [Pt(SO.sub.4)(H.sub.2 
O)(n--C.sub.4 H.sub.9 NH.sub.2).sub.2 ] 
Concentrated sulphuric acid (7 ml, 0.13 mol) was added to a chilled, 
stirred solution (42 ml) of the n-butylamine diaquo complex (0.024 mol). 
After storage at 5.degree. C. for 3 days white chrstals appeared, which 
were filtered off on a porosity 3 sinter and washed with water. The 
crystals effloresced on washing to form a white powder, which was dried in 
vacuo at 50.degree. C. 
Crude yield=2.1 g (19%). 
The complex was insoluble in hot water, ethanol, aqueous sodium sulphate 
solution, methanol and acetone. However, the complex was soluble in 
concentrated sulphuric acid and was recrystallised as follows. 
The crude sulphato complex (0.8 g) was dissolved in 1 ml of warm 
concentrated sulphuric acid on a porosity 4 sintered glass filter. The 
yellow solution so formed was then drawn through by suction into a 
receiver flask containing ice-cold water (2 ml). This gave a white 
precipitate which was filtered off, washed with ethanol and dried in 
vacuo. 
Yield=0.4 g (overall yield=9.5%). 
______________________________________ 
Elemental Analysis 
Pt C H N 0 S 
______________________________________ 
Calculated % 
42.8 21.1 5.3 6.2 17.6 7.0 
Found % -- 20.8 5.2 6.1 -- -- 
______________________________________ 
Infra-red Spectrum 
The nitrogen-hydrogen stretching modes (.nu..sub.N--H) occur at 3220 and 
3120 cm.sup.-1 and there are sulphate absorptions at 1170, 1115, 1030 and 
940 cm.sup.-1. 
EXAMPLE 8 
Bis (n-butylamine)oxalatoplatinum(II), [Pt(C.sub.2 O.sub.4)(n--C.sub.4 
H.sub.9 NH.sub.2).sub.2 ] 
A solution of the n-butylamine diaquo complex (37 ml, 0.024 mol) was added 
to a warm stirred solution of potassium oxalate (13 g, monohydrate, 0.07 
mol) in 40 ml of water. The white precipitate so formed was stirred for 30 
minutes, filtered off on a porosity 4 sinter, washed with water and dried 
in vacuo at 50.degree. C. 
Crude yield=5.4 g (50%). 
The crude oxalto complex was recrystallised as follows. The product was 
added to a stirred, vigorously boiling aqueous solution of 0.1 M potassium 
oxalate (800 ml). The solution was boiled for 30 minutes to effect 
dissolution during which time the solution darkened owing to some platinum 
formation. The solution was then treated with charcoal, stirred, cooled to 
80.degree. C. and filtered through a porosity 4 sinter. White crystals 
formed on cooling the filtrate to 25.degree. C. and after storage for 3 
days at 5.degree. C., the product was filtered off, washed with water and 
air dried. 
Yield 0.2 g (2%). 
The low yield is due to instability of the product in boiling 0.1 M 
potassium oxalate. 
______________________________________ 
Elemental Analysis 
Pt C H N O 
______________________________________ 
Calculated % 
45.4 28.0 5.2 6.5 14.9 
Found % -- 27.2 5.1 6.3 -- 
______________________________________ 
Infra-red Spectrum 
The nitrogen-hydrogen stretching modes (.nu..sub.N--H) occur at 3200 and 
3110 cm.sup.-1 and there are oxalate absorptions at 1695 and 1669 
cm.sup.-1 due to the carbonyl stretching vibrations (.nu..sub.C.dbd.O). 
The spectra of the crude iso- and n-butylamine oxalato complexes showed 
strong peaks at 775 and 1300 cm.sup.-1. These peaks were absent from the 
spectra of the recrystallised compounds. 
EXAMPLE 9 
Oxalatobis(n-propylamine)platinum(II) [Pt(C.sub.2 O.sub.4)(n-C.sub.3 
H.sub.7 NH.sub.2).sub.2 ] 
A warm saturated aqueous solution of potassium oxalate (38 g, monohydrate, 
0.20 mol) was added to a solution of the n-propylamine diaquo complex (120 
g, 0.04 mol). The white precipitate so obtained was stirred for 1 hour at 
50.degree. C., filtered off on a porosity 3 sinter, washed with water and 
dried in vacuo. 
Crude yield=10.8 g (67%). 
The crude product (5.8 g) was dissolved in a vigorously boiling solution of 
K.sub.2 C.sub.2 O.sub.4.H.sub.2 O (13 g, 0.07 mol) in 700 mls of water. 
The clear pale yellow solution formed was treated with charcoal, stirred, 
cooled to 80.degree. C., filtered through a porosity 4 sinter and allowed 
to cool to 25.degree. C. during which time crystallisation occured. The 
mixture was chilled at 5.degree. C. overnight and the crystals were 
filtered off on a porosity 3 sinter, washed with water and dried in vacuo. 
Yield=48% (based on crude produce). 
______________________________________ 
Elemental analysis 
Pt C H N O 
______________________________________ 
Calculated % 
48.6 23.9 4.5 7.0 16.0 
Found % -- 23.5 4.5 6.8 -- 
______________________________________ 
Infra-red spectrum 
The nitrogen-hydrogen stretching modes (.nu..sub.N--H) occur at 3250 and 
3150 cm.sup.-1 and there are oxalate absorptions at 1695, 1680 and 1655 
cm.sup.-1 due to the carbonyl stretching vibrations (.nu..sub.C.dbd.O). 
EXAMPLE 10 
cis-aquabis(n-butylamine)sulphato platinum (II) cis-[Pt(SO.sub.4)(H.sub.2 
O)(n-C.sub.4 H.sub.9 NH.sub.2).sub.2 ] 
Concentrated sulphuric acid (26 ml, 0.49 mole) was added dropwise to a 
stirred aqueous solution of n-butylamine diaquo complex (43 ml, 0.049 
mole) after cooling to 5.degree. C. The solution, after storing overnight 
at room temperature, deposited a white precipitate, which was filtered off 
on a porosity 3 sinter, washed successively with a small amount of cold 
water and ethanol and dried in vacuo at 60.degree. C. Yield of crude 
product=3 g. 
______________________________________ 
Assay: 
Pt C H N O S 
______________________________________ 
Calculated % 
42.8 21.1 5.3 6.2 17.6 7.0 
Found % -- 21.0 5.0 6.5 -- -- 
______________________________________ 
Infra-red spectrum 
The .nu..sub.N--H modes occur at 3210 and 3140 cm.sup.-1, sulphate absorbs 
at 1127 and 1106, 1021 and 936 cm.sup.-1, and water absorptions occur at 
1609 and 3500 cm.sup.-1. 
EXAMPLE 11 
Preparation of cis-aquabis(n-propylamine)sulphato platinum(II) 
cis-[Pt(SO.sub.4)(H.sub.2 O)(n-C.sub.3 H.sub.7 NH.sub.2).sub.2 ] 
The n-propylamine diaquo complex (0.068 mole, assuming 100% conversion) was 
cooled to 5.degree. C. and concentrated sulphuric acid (37 ml, 0.68 mole) 
was added dropwise so that the temperature of the solution did not rise 
above 20.degree. C. After addition of H.sub.2 SO.sub.4 was complete the 
solution was stirred for an hour during which time a small amount (0.5 g) 
of a white solid precipitated. After filtration the filtrate was allowed 
to stand for 5 days and some white needles separated. These were filtered 
off on a porosity 3 sinter, washed with ice cold water and ethanol and 
dried in vacuo at 80.degree. C. 
Yield=4.6 g (15%). 
______________________________________ 
Assay: 
Pt C H N O S 
______________________________________ 
Calculated % 
45.64 16.86 4.72 6.55 18.72 7.50 
Found % -- 17.12 4.19 6.16 -- -- 
______________________________________ 
Infra-red spectrum 
.nu..sub.N--H occurs at 3220 and 3130 cm.sup.-1, sulphate absorptions are 
found at 1230, 1110, 1010 and 993 cm.sup.-1, water absorptions occur at 
1595 and 3500 cm.sup.-1. 
EXAMPLE 12 
Oxalatobis(n-pentylamine)platinum(II) [Pt(C.sub.2 O.sub.4)(n--C.sub.5 
H.sub.11 NH.sub.2).sub.2 ] 
A solution of the n-pentylamine diaquo complex (45 mls, 0.035 mol) in 
aqueous ethanol was added to a solution of K.sub.2 C.sub.2 O.sub.4.H.sub.2 
O (32 g, 0.17 mol) in 100 mls of water, to form a fine white precipitate 
after 5-10 seconds. The mixture was stirred for 30 minutes and the product 
filtered off on a porosity 3 winter, washed well with hot water and dried 
in vacuo at 60.degree. C. 
Crude yield=5.8 g (36%). 
The complex was recrystallised from hot ethanol without apparent 
decomposition i.e. the crude product (2.8 g) was dissolved in approx. 150 
mls of boiling ethanol. The solution was concentrated to a volume of 30-40 
mls, treated with charcoal and filtered through a porosity 4 sinter. A 
white solid formed when the solution was cool. This was filtered off on a 
porosity 3 sinter. More white solid was obtained when an equal volume of 
water was added to the ethanolic filtrate. The purified products were 
combined, washed with water, ethanol and dried in vacuo. 
Yield=1.7 g (overall yield=22%). 
______________________________________ 
Elemental Analysis 
[Pt(C.sub.2 O.sub.4)(n-C.sub.5 H.sub.11 NH.sub.2)] 
Pt C H N O 
______________________________________ 
Calculated % 
42.7 31.5 5.6 6.2 14.0 
Found % -- 31.8 5.6 6.2 -- 
______________________________________ 
Intra-red spectrum 
The nitrogen-hydrogen stretching modes (.nu..sub.N--H) occur at 3200 and 
3110 cm.sup.-1 and there are oxalate absorption at 1693 and 1667 cm.sup.-1 
due to the carbonyl stretching vibration (.nu..sub.C.dbd.O). 
EXAMPLE 13 
Cis-bis(chloroacetato) bis(n-pentylamine)platinum(II), cis-[Pt(ClCH.sub.2 
CO.sub.2).sub.2 (n-C.sub.5 H.sub.11 NH.sub.2).sub.2 ] 
A solution of potassium chloroacetate, prepared from chloroacetic acid 
(19.7 g, 0.21 mol) and potassium hydroxide (11.8 g, 0.21 mol) in 100 mls 
of water, was added to a solution of the n-pentylamine diaquo complex 
(0.07 mol) in aqueous ethanol (90 mls) at 25.degree. C. This gave a brown 
oil. The mixture was stirred for 30 minutes and allowed to stand for 60 
hours during which time the oil hardened to a brown solid. The solid was 
filtered off on a porosity 3 sinter, washed well with water, air dried, 
washed with diethyl ether and then dried in vacuo at 60.degree. C. 
Crude yield=14.0 g (36%). 
The crude product (8 g) was added to 30 mls of boiling ethanol. The brown 
solution was stirred with charcoal, filtered hot through a porosity 4 
sinter and allowed to cool. This gave a white solid which was filtered off 
through a porosity 3 sinter, and washed with ethanol. 
Yield=4.8 g (overall yield=22%). 
______________________________________ 
Elemental analysis 
Pt C H N O Cl 
______________________________________ 
Calculated % 
35.1 30.2 5.4 5.0 11.5 12.7 
Found % -- 29.9 5.5 5.0 -- -- 
______________________________________ 
Infra-red spectrum 
The nitrogen-hydrogen stretching modes (.nu..sub.N--H) occur at 3200, 3160 
and 3110 cm.sup.-1 and there are chloroacetate absorptions at 1600 
cm.sup.-1 owing to the carbonyl stretching vibrations. 
EXAMPLE 14 
cis-[PtCl.sub.2 (n--C.sub.3 H.sub.7 NH.sub.2).sub.2 ] 
Concentrated hydrochloric acid (50 ml.) was added to a solution of the 
n-propylamine diaquo complex and stirred at 40.degree. C. for two hours. 
The slurry of crude product was cooled overnight, filtered and the residue 
washed with water ethanol and dried in vacuo. The crude product was 
recrystallised from NN dimethylformamide (500 ml) by addition of 1 liter 
of 0.1 N hydrochloric acid. 
Yield: 36.7 g, 80% (based on 64 g [PtI.sub.2 A.sub.2 ]). 
IR.nu. Pt-Cl 320 cm.sup.-1. 
EXAMPLE 15 
cis-[PtCl.sub.2 (n--C.sub.4 H.sub.9 NH.sub.2).sub.2 ] 
This complex was prepared in an identical manner to that described in 
Example 14. 
Yield=62%. 
EXAMPLE 16 
cis-dichlorobis(1-aminopentane)platinum(II) 
n-amylamine (0.70 g; 8 m.mol) was added to a solution of K.sub.2 PtCl.sub.4 
(1.66 g; 4 m.mol) in water (15 ml) and sufficient methanol (5 ml) was 
added in order to produce a homogeneous solution. The reaction mixture was 
left overnight and the pale yellow solid that separated was filtered off, 
and washed successively with hot, 6 M hydrochloric acid, water, acetone, 
methanol, and ether. 
______________________________________ 
Analysis: 
C H N 
______________________________________ 
Calculated % 27.3 5.95 6.4 
Found % 27.0 5.80 6.3 
______________________________________ 
The following complexes were prepared in a similar way: 
cis-dichlorobis(1-aminohexane)platinum(II) 
cis-dichlorobis(1-aminoheptane)platinum(II) 
cis-dichlorobis(2-aminoheptane)platinum(II) 
cis-dichlorobis(1-aminooctane)platinum(II) 
Clinical Testing Data 
Complexes according to the invention were tested for antitumour activity 
against L-1210 leukaemia, ADJ/PC6A tumour or S180 solid tumour in mice. In 
the results which follow, dosages are quoted in mg/Kg body weight and the 
evaluation of effectiveness (% T/C) against L1210 is calculated as the 
median survival time of treated mice divided by the median survival time 
of untreated (control) mice expressed as a percentage. Thus a % T/C of 100 
indicates no activity and a % T/C of greater than or equal to 125 is 
considered to be indicative of significant antitumour activity. 
Against a solid tumour, the % T/C is a measure of tumour regression and is 
the percentage of tumour weight in treated mice to that in control mice. 
Against ADJ/PC6A and S180, several dose levels were given and ranged from 
lethal to non-tumour inhibitory, allowing the calculation of LD.sub.50 and 
ID.sub.90 (minimum dose to cause 90% tumour inhibition) in one experiment. 
The ratio LD.sub.50 /ID.sub.90 is the therapeutic index and is a measure 
of the selectivity of the compound as an anti-tumour agent. All compounds 
were administered intraperitoneally as a single dose suspended in arachis 
oil. 
______________________________________ 
Bis(n-propylamino)bis(chloroacetato)platinum(II) 
L1210 Single dose @ 12 mg/Kg % T/C = 167 
@ 24 mg/Kg 5 T/C = 167 
Daily dose for 9 days 
@ 6 mg/Kg % T/C = 225 
______________________________________ 
Bis-(n-propylamino)oxalatoplatinum(II) 
L1210 Single dose @ 59 mg/Kg % T/C = 129 
Daily dose for 9 days 
@ 15 mg/Kg % T/C = 143 
@ 30 mg/Kg % T/C = 143 
______________________________________ 
Bis-(n-butylamine)-bis-(chloroacetato)platinum(II) 
L1210 Single dose @ 256 mg/Kg % T/C = 107 
Daily dose for 9 days 
@ 32 mg/kg % T/C = 136 
______________________________________ 
Bis-(ethylamine)oxalatoplatinum(II) 
ADJ/PC6A ID.sub.90 = 3.9 
LD.sub.50 = 38 
TI = 0.7 
S180 (carrier water) 
T/C = 21% @ 10 mg/Kg 
______________________________________ 
Cis-bis(n-propylamine)dichloroplatinum(II) 
ADJ/PC5A ID.sub.90 = &lt;12 
LD.sub.50 = 26.5 
TI = =&gt;2.2 
L1210 Single dose @ 8 mg/Kg % T/C = 157 
Daily dose for 9 days 
@ 4 mg/kg % T/C = 157 
______________________________________ 
Cis-bis-(n-butylamine)dichloroplatinum(II) 
ADJ/PC6A ID.sub.90 = &lt;10 
LD.sub.50 = 110 
TI = &gt;11 
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Cis-bis-(n-pentylamine)dichloroplatinum(II) 
ADJ/PC6A ID.sub.90 = 37 
LD.sub.50 = 92 
TI = 2.5 
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