DE2402908A1 - 7- (OXOALKYL) -1,3-DIALKYLXANTHINE, METHOD OF PREPARATION AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS - Google Patents

Description

404 Neuss am Rhein, Stresemannallee 6

¹¹ 7 ~ (0xoalkyl) ~ 1,3 ~ dialkylxanthines, process for their preparation and pharmaceuticals containing these compounds "

In DT-AS 1 233 405 the representation of 7- (0xoalkyl) -1,3-dimethylxanthines described. These compounds are pronounced as vasodilating substances with low levels Toxicity described. In addition, the representation of 1- (0xoalkyl) -3,7-dimethylxanthines is known from DT-AS 1 235 320. These compounds also show a significant vasodilator effect.

It has now been found that certain previously unknown 7- (oxoalkyl) -1,3-dialkylxanthines have a pronounced have skeletal muscle blood flow-increasing effect with low toxicity.

The present invention accordingly provides

509830/0934

2A02908

7- (Oxoalkyl) -1,3-dialky! Xanthines of the general formula I.

■ Ν

-N-A-C-CH,

I "O

(D

in the R ^ and Rp the same and / or different straight-chain or branched alkyl radicals with 2 to 6 carbon atoms, cyclohexyl, alkoxyalkyl and hydroxyalkyl radicals and A is a hydrocarbon means a remainder with up to 4 carbon atoms which can still be substituted by a methyl group.

The compounds claimed are prepared in a manner known per se by being carried out at elevated temperatures and optionally in the presence of a solvent either

a) appropriately substituted 1,3-dialkylxanthines of the general Formula II

(H)

509830/0934

in which R ₁ and Rp have the meaning given above, at an elevated temperature in an alkaline medium with cX, ß-unsaturated methyl ketones of the general formula III

H ₂ C = C - C - CH ₃

(III) RO

in which R is hydrogen or a methyl group, or

b) Alkali metal salts of the 1,3-dialkylxanthine derivatives of the general formula II, in which R 1 and R _{2 have} the meaning given above, with oxoalkyl halides of the general formula IV

CH ₃ - C - A - shark

in which A has the meaning given above and Hai is a halogen atom, is preferably bromine or chlorine.

The reactions described above are preferably carried out at temperatures from 40 to 8O ⁰ C, optionally at elevated or reduced pressure, but usually at atmospheric pressure is performed. The individual starting compounds can be used in stoichiometric amounts or in excess. The alkali salts in process b) can be prepared either beforehand or in the reaction itself.

5 0 9830/0934

Compounds which are miscible with water can be used as solvents, preferably lower alcohols such as methanol, propanol, Isopropanol and the various butanols, also acetone, pyridine, triethylamine, polyhydric alcohols such as Äthy.lenglykol, and ethylene glycol monomethyl / (ethyl) ether.

The compounds prepared according to the invention are distinguished characterized by a pronounced skeletal muscle blood flow-increasing effect with low toxicity. Shows the most pronounced effect 7- (3-oxobutyl) -1,3-di-n-butylxanthine.

The invention accordingly also relates to medicaments which contain a compound according to formula I as an active ingredient.

The experiments below illustrate this effect. They were tested on male and female cats (under urethane-chloralose anesthesia) carried out. The substances were in methyl cellulose suspension applied intraduodenally. Blood pressure, heart rate and blood flow were recorded in the usual way Statham transducers or heat conduction probes determined. The data obtained (cf. Table I) show that the skeletal muscle blood flow is demanding Effect that clearly exceeds that of comparison substances, e.g. pentoxyphylline (cf. Table ΪΙ). The ratio of increasing blood flow the skeletal muscles and the increase in heart rate is beneficial. The results obtained are graphical in Figs reproduced.

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Table I 7- (3-Oxobutyl) -1,3-di-n-buty! Xanthine

Blood pressure (BP) ldcat
Change in % Duration in minutes 5 mg / kg
12.6 mg / kg
31.5 mg / kg
63.0 mg / kg + 10.5
+ 9.7
+ 9.7
- 7.7 38.8
57.3
40.0
25.0 Heart rate (HR) Change in % Duration in minutes 7 mg / kg
12.6 mg / kg
31.5 mg / kg
63.0 mg / kg + 12.7
+ 13.8
+ 7.1
. - 0.9 > 49.0
55.9
61.0 ".
40.0 Skeletal muscles
Heat transfer number Change in % Duration in minutes 5 mg / kg
12.6 mg / kg
31.5 mg / kg
63.0 mg / kg ■ + 28.8
+ 29.3
+ 24.5
+ 12.0 72.0
77.0
75.0
26.0

N = 6 at all dosages

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2A029Q8

Table II Pentoxyphylline in Cat

Blood pressure (BP) Change in % Duration in minutes 5 mg / kg + ° - 10 mg / kg + 3 10 30 mg / kg + 3 19th 50 mg / kg - 3 > 28 Heart rate (HR) Change in % Duration in minutes + 9 7 27 5 mg / kg , + 10 > 30 10 mg / kg + 20 •> 21 - 30 mg / kg + 10 ? 2β 50 mg / kg Change in % Duration in minutes Skeletal muscles
Heat transfer number + 10 20th + 4 12th 5 mg / kg + 2 17th 10 mg / kg + 0 - 30 mg / kg 50 mg / kg

509830/0934

_{The influence on the pC ^ »pC0 2} and PH of the arterial and venous blood was investigated in hybrid dogs (under urethane-chloralose anesthesia). For this purpose, blood was taken from the aortic artery and the femoral vein at intervals of 5 minutes.

The test substances, namely 7- (3-oxobutyl) -1,3-di ~ n-butylxanthine and pentoxyphylline for comparison, were given intravenously.

The results are shown in the attached curves (Figs. 3 and 4). -

The single administration of 30 mg 7- (3-0xobutyl) -1,3-di-n-butylxanthine per kg iv shows that this substance significantly reduces the pO _{2 in} both the arterial and venous limbs of the circulatory system for at least 70 minutes elevated. This pO «increase is longer lasting than that of pentoxyphylline.

The LD 50 of the compound in the mouse is over 1000 mg / kg per os and 134 mg / kg i.v.

Investigations on rat brain in vivo showed after a single Administration of 100 mg / kg 7- (3-0xobutyl) -1,3-di-n-butylxanthine p.o. compared to a control with methyl cellulose suspension increased oxygen consumption (cf. Table III and FIG. 5).

When studying parameters from fat and carbohydrate metabolism shows the connection does not have the usual properties · ■ Shafts of xanthine derivatives, such as increasing lipolysis and Increase in glucose and lactate levels in the blood from normal, al-

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rats and the potentiation of the adrenaline effect. On the contrary, the administration of 7- (3-0xobutyl) -1,3-di-n-butylxanthine some of the parameters mentioned are significantly reduced or the changes brought about by adrenaline not raised to the power further (see Tables IV to VI).

The other compounds of the present invention show similar results strong pharmacological effect.

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cn o co

Table III !1
Page 9 - Weight,
G * 10 min. 20 min. 30 min. 40 min. . -921.7 50 min. 60 min. Fresh weight rat brain in vivo (in methyl cellulose suspension) 172 -250.7 -458.3 -654.5 -831.8 -754.5 -970.1 -1132.0 / Ul Og - abuse / g] + 100 ing / kg 7- (3-0xobutyl) -1,3-di-n-buty! Xanthin po 2 ⁿ before killing 186 -207.5 -407.6 -596.5 i -763.8 -752.9 -920.1 -1105.3 177 -275.0 -520.3 -728.4 -699.8 -1100.1 -1189.3 Animal no.
? 176 -183.0 -426.8 -602.0 -763.1 -914.5 -1059.3 1 187 -197.9 -395.6 -586.4 -698.7 -915.6 -1064.4 ** 2 176 -197.1 -370.3 -546.9 -805.7 -862.9 -995.3 3 205 -220.1 -429.7 -606.8 -861.6 -940.9 -1083.6 4th 200 -209.7 -349.6 -535.0 -850.7 -1014.9 5 198 -233.3 -438.2 -646.7 -785.4 -978.8 -1109.6 6th 196 -224.6 -436.9 -649.2 4.2 -1012.6 -1269.9 7 · - N) • 8th 187 -219.9 -423.3 -614.3 -946.6 -1102.4 ο 9 3.6 4.3 3.8- 4.4 10 2 ^ 10 - - - - ρ <0.01 § 0 % significance

Table III (continued)

o> ta ο

Weight,
G 10 min. K ο η trolls 30 min. .0. ) 50 min. 60 min. • N)
<£>
O
CP 184 -217.7 (Methyl cellulose suspension ρ -598.6 40 min. -945.8 -1024.8 Animal no. 162 -220.5 -580.0 -757.8 -918.4 -1004.9 1 175 -235.7 -683.8 -750.7 -1026.9 -1106.8 2 165 -213.5 -575.8 -908.2 -899.2 -989.8 3 166 -194.3 -556.2 ' -737.5 -817.5 -931.5 4th 185 -192.5 -544.2 -690.2 -829.6 -929.2 5 202 -207.2 -594.0 -703.5 -918.6 -1015.3 6th 181 -184.4 -520.6 -759.7 -834.3 -973.4 7th 179 -245.0 -638.7 -698.4 -942.7 -1030.4 8th 192 -211.1 -626.3 -787.5 -930.9 -997.7 9 -746.9 10 179 -212.2 -591.8 -906.4 -1000.4 -754.0 0 20 min. -428.7 -404.6 -484.6 ' -388.2 -388.7 -358.4 -393.7 -371.9 -424.9 -415.3 -405.9

Table IV

η- (5-oxobutyl) -1,3-di-n-butylxanthine

Rats, 5 fasting, ether anesthesia, cardiac puncture Method: Boehringer test set

2A02908

- Glucose level side

Ti I. Normal ar no. Ge
weight
G ^E 1 ^E 2 E ₂ - E ₁ mg % (Methyl cellulose
Suspension ρ.ο.)
2 ^hours before killing 1 181 0.055 0.186 0.131 113.18 0 117.07
II. 7-73-oxobutyl) - 2
4th
5
6th
1 176
183
168
172
170
178 0.062
0.061
0.064
0.057
0.062
0.057 0.200
0.213
0.182
0.207
0.186
0.189 0.138
0.152
0.118
0.150
0.124
0.132 119.23
131.33
101.95
129.60
107.14
114.05 *. 1 ♦ 3-di-n-butyl-
xanthine 2
3 188
193 0.059
0.062 0.184
0.187 0.125
0.125 108.00
108.00 100 mg / kg p.o. 4th 189 0.062 0.182 0.120 103.68 2 before killing 5
6th 163
198 0.058
0.064 0.183
0.192 0.125
0.128 108.00
110.59 0 108.72 1 177- 0.049 0.328 0.279 241.06 III. adrenaline 2 170 0.062 0.292 0.230 198.72 1 mg / kg i.p. 3
4th
5
6th
7th
8th
9
10
11
12th 174
189
159
173
152
163
168
168
160
163 0.058
0.057
0.065
0.074
0.073
0.077
0.078.
0.074
0.073
0.075 0.370
0.203
0.339
0.242
0.319
0.274
0.364
0.296
0.271
0.286 0.312
0.146
0.274
0.168-
0.246
0.197
0.286
0.222.
0.198
0.211 269.57
126.14
236.74
145.15
212.54
170.21
247.10
191.81
171.07
182.30 30 »from killing 1 191 0.056 0.285 0.229 197.86 0 199.36 2
3 165
185 0.053
0.055 0.180
0.251 0.127 '
0.196 109.73
169.34 IV.7- (3-oxobutyl) - 4th 176 0.063 0.268 0.205 177.12 1,3-di-n-butyl
xanthine 5
6th 199
181 0.070
0.069 0.199
0.330 0.129
0.261 111.46
225.50 100 mg / kg body weight 7th
8th
9
10
11 152
163
161
169
162 0.068
0.073
0.064
0.069
0.073 0.193
0.193
0.261
0.262
0.296 0.125
0.12Q
0.197
0.193
0.223 108.00
103.68
170.21
166.75
192.67 h ^oral
2 before killing 12th 178 0.083 0.288 0.205 177.12 +
adrenaline 1 mg / kg i.p. 30 * before killing R <0.05
0 159.12

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Table V -I, 3 ~ di-n-butylxanthine L a k t a t mirror

Vt

Rats, 5 sober, ether intoxication, cardiac puncture Method: Boehringer test cutlery

Animal no. weight
G ^E P ^E L ^E P- ^E L mg % I. Normal 1 . 181 0.312 0.079 0.233 21.9 (Methylcellu- 2 176 0.277 0.079 0.198 18.6 loose-suspen- 3 183 0.345 0.079 0.266 25.0 sion)
4 ml / kg body weight po 4th 168 0.302 0.105 0.197 18.5 5 172 0.325 0.105 0.220 20.7 2 before killing 6th 170 0.358 0.105 0.253 23.8 ft 7th 160 0.328 0.095 • 0.233 21.9 • 8th 164 0.275 0.095 0.180 16.9 9 170 0.333 0.095 0.238 22.4 10 160 0.415 0.095 0.320 30.1 11 167 0.405 0.095 0.310 29.2 Bsasma: 3S3snssss: sass3Sssssrras = SS3BS! 3SS ~~ S 0 22.6

Table V (continued)

Animal no. weight
G ^E P ^E L ^E P- ^E L mg % II. 7- (3-OxObUtVl) -
1,3-di-n-butyl-
xanthine 1
2
3 178
188
193 0.321
0.230
0.286 0.079
0.079
0.079 0.242
0.151
0.207 22.8
14.2
19.5 100 mg / kg body weight po
2 ^hours before killing 4th
5
6th 189
163 ■
198 0.27't
0.234
0.224 0.105
0.105
0.105 0.169
0.129
0.119 15.9
12.1
11.2 7th 152 0.242 0.095 0.147 8th ■ 157 ■ 0.252 0.095 0.157 14.8 9 153 0.355 0.095 0.260 24.5 10 • 149 0.274 0.095 0.179 16.8 11 172 0.235 0.095 0.140 13.2 P < 0.01 0 16.2

NJ 40 O CO

Table V (continued)

Animal no. weight
G ^E P ^E L. .% - ^E L mg % III. adrenaline 1 189 0.730 0.079 0.651 61.3 1 mg / kg body weight ip
30 »v. Kill 2
3
4th
5
6th 194
159
173
148
.156 0.345
0.76ε.
0.631
0.763
0.495 0.105
0.105
0.105
0.105
0.105 0.240
0.663
0.526
0.658
0.390 22.6
62.4
49.5
61.9
36.7 0 49.0 IV.7- (3-0xobutvl) -1.3-di-
n-butylxanthine
100 mg / kg body weight po '
2 ^hrs . Kill
adrenaline 1
2
3
4th
5
6th 191
.165
185
176
199
181 0.638
0.506
0.622
0.850
0.552
0.705 0.079
0.079
0.079
0.105
0.105
0.105 0.559
0.427
0.543
0.745
0.447
0.600 52.6
40.2
51.1
70.1
42.1
56.5 1 mg / kg body weight ip
30 'v. Kill 0 52.1 SS SStSSSS! S3 SS SS SS SSSSSS S3 : = = = ====: ==: =: T m Πη - "" Τ - ~ ■ «·" W ΪΒ "1ϊη STTtF" - - - - «- ——. - - - --- | j. BaansassssBssssssssassssaas! =

Table VI

Serum fatty acids FFS inh

7- (3-oxobutyl} -1 ^ 3-di-n-butylxanthine _1.6O_mg / kg

Method: Acta Biol. B J. \ ei λ O i) 2 0 (1964) / U val / ml Animal no. Weight,
S. 1.12 1 151 0.99 Control row 2 155 0.87 ' 3 160 Π fV7 (Methyl cellulose suspension) Λ 1 * 7R U, O /
0.81 4 mg / kg body weight p.o. «+
5 I 10
168 0.73 2 before killing 6th 160 0.72 7th 213 ' 0.76 8th 200 1.10 9 160 0.99 10 150 ' 0.90 0 169 0.68 1 151 0.76 2 152 0.75 7- (3-0xobutvl) -1,3-di-n- 3 152 0.57 butylxanthine 4th 188 0.81 160 mg / kg body weight p.o. . 5 165 0.96 6th 170 1.07 2 ⁿ before killing 7th 190 1.02 8th 190 0.95 9 190 0.90 10 184 1.02 11 203 1.14 12th 152 0.89 0 174 ._ _ ___.__. "-. ——— ..-.-.—— ..« - j --..... ——-

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Table VI (continued)

Animal no. 0 ^Weight:
G / U val / ml 1 161 1.23 2 152 1.36 adrenaline 3
Λ 177 1.09
1 17 1 mg / kg body weight i.p. 5 172 ι, ι /
1.17 30 'before killing .6 167 1.10 7th 139 1.52 8th 133 1.60 9 149 1.73 10 0 147 1.49 11 140 1.45 12th 142 1.31 "154 1.35 7- (3-oxobutyl) -1,3-di-n- 1 160 0.84 butylxanthine 2 152 0.99 160 mg / kg body weight ρ.ο. 3 150 0.96 2 ^hours before killing 4th
ρ; 168
160 1.28
1 ^ 6 + J
6th 181 1.39 adrenaline 7th 166 1.72 1 mg / kg body weight i.p. 8th 146 1.46 30 ^f before killing 9
10 142
143 1.67
1.65 157 1.33

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2Ä02908

- 17 The following examples illustrate the invention.

Example 1 7- (3-Oxobutyl) -1,3-di-n-butylxanthine

In a 3 liter three-necked flask, 264.8 g (1 mol)

1,3-di-ri-butylxanthine, 84 g (1.2 mol) methyl vinyl ketone, 1060 ml

Methanol and 39.7 ml of triethylamine are combined and the mixture is slowly heated to 40 to 45 ° C. while stirring. The reaction solution is kept at this temperature until there is practically no 1,3-di-n-butylxanthine in thin-layer chromatography more can be pointed out. Reaction time approx. 2 to 2.5 hours. . '·

After the reaction has ended, enough water is added to this solution in small portions that an approx. 75 to 80 percent aqueous methanolic solution is formed; this is left to stand in the refrigerator for several hours and the resulting crystals are sucked off away. Another recrystallization from methanol-water gives 276 g = 80 percent of the theory 7- (3-oxobutyl) -1,3-d.i-n-butylxanthine from melting point 86 to 87 ° C.

Concentration of the methanolic mother liquors gives additional another 24 g of 7- (3 ~ 0xobutyl) -1,3-di-n-butylxanthine. Overall yield: 300g £ 87 percent of theory.

Analysis: C H N 0

calculated: 61.06 7.84 16.75 14.35 %

found: 60.92 7.81 16.96 ■ 14.34 %

509830/0934

2A02908

In a corresponding manner, according to variant a) of the claimed Process prepared the compounds listed in Table VII below.

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Table VII

at
spat]
No. R ₁ ^R 2 ■ R. A. Melting point C.
solvent
for recrystalline
lization the end
prey
d.Th. Combustion Analysis:
CHNO
(calc .: +) (found .: ++) 1 Xi-C ₄ H ₉ - HC ₄ H ₉ - -H -CH ₂ -CH ₂ - 86-87
Methanol / water 87 + 61.06 7.84 16.75 14.35
++ 60.92 7.81 16.96 14.34 2 ⁿ - ^c 4 ^H ₉ - HC ₄ H ₉ - -CH,
3 -CH-CH ₀ -
CH ₃ 46
Gasoline / ethanol 79 + 62.05 8.10 16.08 13.78
++ 62.20 8.13 16.02 13.52 3 -CH- (CH ₃ ) ₂ -CH- (CH ₃ ) ₂ -CH-.
3 -CH-CH ₀ -
t * -
CH ₃ 91
petrol 77 + 59.98 7.55 17.49 14.98
++ 60.15 7.39 17.24 15.40 4th -CH- (CH ₃ ) ₂ -CH- (CH ₃ ) ₂ -H -CH ₂ -CH ₂ - 73
Ethanol 80 + 58.81 7.24 18.29 15.67
++ 59.13 7.28 18.09 15.52

Example 5 7- (5'-Oxohexyl) -1,3-dibutylxanthine

In a 500 ml flask, 21.5 g (0.12 mol) of freshly distilled 1-bromohexanone- (5) in 200 ml of abs. Ethanol and dissolved in the boiling point 34.7 g (0.12 mol) 1,3-dibutylxanthine sodium, dissolved in 200 ml of abs. Ethanol, gradually added dropwise. The solution is heated to reflux. After about 24 hours the. Reaction ended. After the alcohol has been distilled off on a rotary evaporator, a solid white residue remains. This is placed in an extraction thimble and extracted with gasoline 40/80 in a Soxhlet apparatus until there is no starting material is more detectable. The gasoline is distilled off on a rotary evaporator. There are 25 g (0.069 mol) of 7- (5'-oxohexyl) -1,3-dibutylxanthine = 75 percent of theory obtained (based on converted 1,3-dibutylxanthine sodium).

The melting point of the crude product is 80 to 82 ° C.

By repeated recrystallization from isopropanol pure 88 ° C is 7- (5 * -Oxohexyl) -1,3-dibutyIxanthin mp. Obtained.

C ₁₉ H ₃₀ N ₄ O ₃ (362.74)

CHNO

calculated: 62.96 8.34 15.48 13.24 %

found: 62.99 8.14 15.34 13.40 %

The residue from the extraction is dissolved in ethanol and separated from the sodium bromide. The solution is concentrated to dryness

509830/0934

and the residue is recrystallized from ethanol; 7.5 g (0.0284 mol) of 1,3-dibutylxanthine are recovered in the process.

In a corresponding YJeise according to variant b) of the claimed Process prepared the compounds listed in Table VIII below.

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Table VIII

CO Ca »O

at
game
No. ^R 1 1
R ₂ R. A. Melting point C.
solvent
for recrystalline
lization the end
prey
%
d.Th. Combustion Analysis
CHNO
(calc .: +) (found .: ++) 5 ⁿ - ^c 4 ^H 9 ~ nC ₄ H _g - -H - (CH ₂ ) ₃ -CH ₂ - 88
Isopropanol 75 + 62.96 8.34 15.48 13.24
++ 62.99 8.14 15.34 13.40 6th -CH- (CH ₃ ) ₂ -CH- (CH ₃ ) ₂ -H - (CH ₂ ) ₃ -CH ₂ - 103 ..
Gasoline / ethanol 71 + 61.06 7.84 16.75 14.35
++ 61.06 7.99 16.94 14.56 7th HC ₄ H ₉ - ⁿ " ^c 4 ^H ₉ - -H -CH ₂ - • ^1o6 ..
Gasoline / ethanol 68 + 59.98 7.55 17.49 14.98
++ 60.00 7.53 17.01 15.51 .8th -CH- (CH ₃ ) ,, -CH- (CH ₃ ) ₂ -H -CH ₂ - 149 ..
Gasoline / ethanol 64 + 57.52 6.90 19.16 16.42 L.
++ 57.81 6.75 18.97 16.54 V. 9 nC ₄ H _g - HC ₄ H ₉ - -H - (CH ₂ ) ₂ -CH ₂ - Gasoline / ethanol 30th + 62.05 8.10 16.08 13.78
++ 61.98 7.86 16.21 14.16 ; ¹⁰ -CH- (CH ₃ J ₂ -CH- (CH ₃ ) ₂ -H - (CH ₂ ) ₂ -CH ₂ - 72 _{t <}
Gasoline / ethanol 35 + 59.98 7.55 17.49 14.98
-H- 60.16 7.40 17.44 14.88 11 nC ₄ H _g - 11-C ₄ H ₉ - -CH ₃ -CH-
I.
CH ₃ 96 ..
Gasoline / ethanol 90 + 61.06 7.84 16.75 14.35
++ 61.17 7.85 16.98 14.10 12th -CH- (CH ₃ ) ₂ -CH- (CH ₃ ) ₂ -CH-,
3 -CH- ·
t
CH ₃ Gasoline / ethanol 53 + 58.81 7.24 18.29 15.67 K.
++ 58.90 7.17 18.27 15.92 O
N)
W.

Claims (6)

Patent claims: in the R ,. and Rp the same and / or different straight-chain or branched alkyl radicals with 2 to 6 carbon atoms, cyclohexyl, alkpxyalkyl and hydroxyalkyl radicals and A is a hydrocarbon means a remainder with up to 4 carbon atoms which can still be substituted by a methyl group. ' 2. 7- (3-0xobutyl) -1,3-di-n-butylxanthine. 3. A method for the preparation of compounds according to claim 1, formula I, characterized in that, s one at elevated temperatures and, if necessary, in the presence a solvent either a) appropriately substituted 1,3-dialkylxanthines of the general Formula II 509830/0934 2Ä02908 -Zk- (II) in the FL, and R2 have the meaning given above, in the case of increased Temperature in an alkaline medium with c <, ß-unsaturated Methyl ketones of the general formula III (III) H ₂ C = C-C-CH ₃ R 0 in which R is hydrogen or a methyl group, converts or b) Alkali metal salts of the 1,3-dialkylxanthines of the general Formula II, in which R ^ and Rp have the meaning given above have, with oxoalkyl halides of the general formula IV CH ₃ - C - A - shark 0 (IV) in which A has the meaning given above and Hai is a Halogen atom, preferably bromine or chlorine, is converted. 4. The method of claim J5> characterized in that one carries out the reaction at temperatures in the range of 40 to 80 ⁰ C. S0983Ö / 0934 5. The method according to claim 3 and 4, characterized in that the solvent used is lower alcohol. 6. Medicament, characterized by the content of a compound according to claim 1, formula 1 as an active ingredient. 509830/0934 Jt6 Blank page