JPS5946222A - Carcinostatic agent - Google Patents

Abstract

PURPOSE:To provide a carcinostatic agent having extremely low toxicity, by using a D-glucose-3-O-alkyl (or alkenyl) ether as an active component. CONSTITUTION:The objective agent contains the compound of formula I (R is 1-30C alkyl or 1-30C alkenyl), e.g. D-glucose-3-O-lauryl ether, as an active component. The compound of formula I can be prepared easily by refluxing the 3-O-alkyl (or alkenyl)-1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose of formula IIin an aqueous solution in the presence of an acid catalyst such as a mineral acid, acidic ion exchange resin, etc. Dose: preferably 1.0-200mg/kg for oral administration and 0.5-100mg/kg for parenteral administration for adult.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides D-glucose-6- and J-alkyl-
relates to an anticancer agent containing an alkenyl ether as an active ingredient.

The present inventors have developed various glucose ether loadings (
Investigation of its embedding effect (2) revealed that D-glucose-6-〇-alkenyl ether has a specific 1jΦ harmful effect,
Completed Honkomashi.

That is, the present invention provides a D-glucose-3-(J-alkyl or alkenyl ether'&N active ingredient) represented by the following formula (1) (wherein R represents an alkyl or alkenyl group having 1 to 6 U) It increases the amount of damage it contains by +3".

The D-glucose-6-(l-alkyl or alkenyl ether of the present invention) is a known compound or is easily a filtrate compound by known methods. For example, Tr, -
Mezhdunar, Kongr, Pooerkh
n, −Akt%Veshcl+estuan, 7t
l]1976 (Pub, 1977,), 1.21
7-1,223(()er), and Nats, Kom
.

5SSFt Pouerkhn, J'J-t
, Vesbchestuarn: MO5COw
.

D-glucose-6- as a W-face C tongue agent in USSR
IJ-, (:'12 argyl ether is disclosed, f, f return prime number 1 to 4 D-glucose-3-U-
Argyl ethers and allyl ethers are also known.

(-Kashina, these things (Hate's enemy, lv1 effect, etc.) (-"♀< q:n were not mentioned.

The anti-layer effect of the D-glucose-lo-〇-alkyl or alkenyl ether (1) of the present invention is specific, and the anti-layer effect is approximately 1//Lo- It becomes weaker with 1 IW.

D-glucose-3=[J-alkyl<(
Airkenyl ether (1) can be prepared according to Example 1 and the following reaction formula.

(In the formula, R is the same as above) That is, 5-o-'ylkyl or alkenyl-1
,2:! l), 6-zo-O-inpropylidene Ltχ-
1] - Gelcofuranose activation is the presence of a catalyst.

It can be prepared easily by refluxing it in a water bath 4).

I praise) As a catalyst, 1 rabbit) Ka, Kan 1 olfactory expansion 11a and -1 Nnomerite I R-120% CG-12
11th grade acid 11 ion sentence I! +! ! l! J fat is used. Reaction (technique) is completed by becoming 1111 flow game J at 3'0 minutes to 5U.

In this way, (44) is converted from the L6 product (1
), the objective I of course is to water.11 If it is a bath, then as it is (reference/I3 excess or 1 of ether)
Ad can be carried out by extraction with a suitable medium, and if the curved material is water-bathable and is used as a water bathing medium, it can be extracted with a suitable alkali etc. After the 11th cycle, the target product is water-soluble; (Metan 1 Fatty King Mausoleum, 7p Licensing C Orpressure! F Waterfall, each done by staying 1 night.
Ru. .

The crude crystals of the 1-carved mortuary (1) are as follows:
-, alcohols such as methanol, ethanol, n-zolopanol, isozolopanol, ketones such as acetone, methyl ethyl ketone, etc.;
11j frame Darko Sue 5-IJ-Argil one unit
can be considered as the four lucky crystals of alkenyl ether.

The starting material for Dou'216 Ming compound is 3-0-alkyl-J L <&X alkenyl-isopropylidene-α-D-glucofuranose ful
Regarding carbon atoms 1, 2, 6, 4, 12, and allyl ethers, there are known 16 compounds or other compounds. These compounds are 1, 2:
5,6-D-isopropylidene-α-D-glucofuranose 31 dissolved in an appropriate solvent, 1 to 2 equivalents + 1'
0,) 1 to 2 equivalents of alkyl or alkenyl halide in the presence of a strong base such as sodium hydride [) to ε3
It can be easily produced by reacting at -0°C for 5 to 10 hours. As a solvent, benzene, toluene, zooginane, detrahydrofuran, zomethylsulfogide, dimethylformamide, etc. can be used, but sometimes dimethylsulfoxy is preferred. That's awesome.

Next, representative compounds of the present invention obtained by analysis are shown in Table 1, and tested for their phosphorescence and bulkiness. - [0 or more margin ill' Leukemia L 4% 5ill l)m as Leukem
ia L-5178Y Begging desk 1,9 action case style bemuni. RPrJI containing 10 doses of fetal bovine serum 1640 Tsubakiike, L-5178Y, 1 cell and 1x1υ5 +11! !
1/lnl, and after adding 4 degrees of R to the sample, heat it at 37°C in a 5% carbon dioxide incubator for 48 hours. ``The end of the battle... Thin) Kaoru Kaoru made a mistake, and compared to the contrast, Po. 11
11 dishes JW top rate r batter 1 piece. This beggar %j is dealt with on the probability paper, and from this ■C50 is determined. This rice is shown in Table 2.

The following margins are 42 tables (2L P 388 (c for +H (1vi work 1-
441 I1°P6 40) I-3D Do1 Thread-11f, regarding the sex mice, 1 animal within 1j heron 11〆 of this mouse 7
is 1 [J51 same P6ε38. Toltl +1lI2
In order to incubate and grow for 24 hours, it is possible to produce 1 kl! f r
K has a ml-decreased chivalry compound ke 1F31 times 6CJn19
/Zeng was cast in 11νlI', E for 5 consecutive days. 4. After winning +11, I obtained ILS (%) from α Todo If Nisshu, and J Maru 1+ from the total 6δ young rice.
￥i + tongue 1〆IE Y *；1mbefko. The results are shown in Table 6.
Inject one mouse into one Mf and administer it to five mice per day, and give it to one mouse for 7 days. Part 1 Fruits and vegetables 5 [
None of the mice were born at the same time as the administration of JOll1y/tag.
is more than 5 o-'ir]ll/My, and poison t'l
: Imakoro - [Weak.

The end of the present invention, lt + r < then f4 +
1.6. +8 drug, Kabushi Ruj1su, 1'Qla1'1su, Shirotsu'7° column, 1:ru4ma ('1 administration,'y,'y, as injection 11th, Ii lower, H4 intramuscular ,III
If in IJ IQ: E, Il+'('Waste meat IX
4 s - h し < は 龜い i etc. (mixed with fish meat), or 川 [あいばくとl 卦C Parenteral administration is also recommended.

Dosage Pd° varies depending on the route of administration and is usually for adults.

In the case of oral administration, i, o ~ 20 o〃v/+C
p.

For parenteral administration, LJ, 5 to 1 uo+w/g is suitable. In 1, 4ν (sodium carboxymethylcellulose, refined abrasion of siderobil cellulose, etc.), IM crystal (lulose, disintegrating agent of calcium methylcellulose, talc, magnesium stearin) Lubricants such as, light 'bo yankkei r dredging?lIe!I:b
A ridge cut, etc.? ] 1st plan: By combining and prescribing, -shavings, capsules, granules, etc. f can be ordered.

In parenteral preparations, when using the injection 41 in the form of an aqueous solution, (i) the invention compound, such as compound number 6, is
Since the product is soaked in physiological saline or the like, injections and the like can be manufactured using conventional methods.

To make a zasha, the compound of the present invention is added to a base commonly used in music, such as cacao butter, synthetic oil, etc., by a conventional method.
Later assimilate and project.

Next, we will introduce the reference field practice 1st 11th grade, and then write the main text.
Explanation: “Ru.

Reference Example 1 Synthesis of D-glucose-3-1,1-lauryl ether: 6-IJ-lauryl-1,2:5.6-C+J'-impropylidene-α-D-glucofuranose 2.07
,</na4 [4,7+l of water (suspended, treated with Amperlite CG-120 (1N+clogged)") 1
．． 511 was added and refluxed for 24 hours. Cold lax suction (J51
Wash with 1φ water. Clean the remaining 11γ methanol! 'Part,
1 unit: Furthermore, when 1 unit is reduced, it crystallizes.

1゜03g of crystals with a residual color of 1゜03g are obtained from Rua Flecole to Isozoro.〕-Glucose-3-0- Octadecyl ether (compound number 13) 10 (JII
l&D-mannitol 150# crystalline cellulose 50) ILy potato den 1 2 Bmycal+l
? oxymethylcellulose calcium talc 4 rtb;
) Magnesium stearate 2 In
9th investigation Ht ( 5 5 0 ”
9 mL + 14 minutes, 11 minutes was prepared using the method.

Example 2 (capsule cutting) Combination! Compound of proboscis number 9' proboscis 2 5 +
11! , 1 crystal cell U-s i
7m9 skewer shield 'if Su1 Mr. Nok Kay 1ri

7 l,7 stearin magnesium
11η9 all io
1801 Remove the above ingredients and make granules 7 using the 'PO method.
Fill the No. 6 cassel 111M once.

Central case 3 (injection) D-glucose-3~E1-ofnal ether (compound number 6) 5 CJm9 raw L! 4! 'IJ Salt/
k Te bath 1% L, spicy acid 2 m13. Membrane filter -? Using Vtli IA i
'The door is filled with glass, melted and sealed, and becomes a princely state.

Cannon 1'/In (emulsified isu for Tonkei) Kozue/Kita V oil I II IJ
g, IH egg yolk lecithin 12! I 25g of lycerin for injections, complete with distilled water for injections, 1,000 pieces of this product 11
1ii Therefore, the slope pressure ratio is approximately 1.

Actual case example 5 (sitting) Compound No. 12 compound's proboscis 5 LI I1
1! Remove the upper layer for 15 minutes, melt in the bath by the usual method, and
- Pushing, assimilating Seino 19 and making 1 piece χ.

Procedural summary document (spontaneous) December L7, 1980 Patent Office 12th official Kazuo Sugi 2 Name of the invention Anticancer agent Address 4, 2-12, Nihon Kuihama-cho, Chuo-ku, Tsukaikito
Name: Nisnis Seiraku Co., Ltd. Representative Name: Nookata Yasumichi 6, "Detailed Description of the Invention" column of the subject matter of extraction.

7, @The immanence of stop (1) Meiwa 1 tatami medium, page 2, bottom row r Veahc
haatuan J and I Vi+@hchem
Revised as tuam J.

(2) In the 1st Tsukasa, 3rd Sada, 3rd line, ``R ussn'' is corrected to ``R USSR, ni''.

Claims (1)

[Scope of Claims] 1 D-glucose-6-o-alkyl or alkenyl represented by the following formula flJ H C formula 'P, R are carbon * alkyl or alkenyl group having 1 to 60 j) Ether is a very useful anticancer agent as an active ingredient.