GB2055576A - Anti-tumor agent - Google Patents
Anti-tumor agent Download PDFInfo
- Publication number
- GB2055576A GB2055576A GB8021580A GB8021580A GB2055576A GB 2055576 A GB2055576 A GB 2055576A GB 8021580 A GB8021580 A GB 8021580A GB 8021580 A GB8021580 A GB 8021580A GB 2055576 A GB2055576 A GB 2055576A
- Authority
- GB
- United Kingdom
- Prior art keywords
- tumor
- tumor agent
- formula
- compound
- mono
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Abstract
An anti-tumor agent comprising, as an active ingredient, at least one compound represented by the formula (I> <IMAGE> wherein each of X<1>, the X<2)<s), and X3 independently represent hydrogen or a single chemical bond, provided that at least two of X<1>, the X<2)<s), and X<3> represent single chemical bonds, R represents hydrogen or an alkyl group, m is an integer of 1 to 4 and n is an integer of 1 to 3. 2.4- monobenzylidenesorbitol, 1.3,2.4 - dibenzylidenesorbitol, 1.3,2.4,5.6 - tribenzylidenesorbitol, 1.3,2.4 - dibenzylidenexylitol, 1.2 - monobenzylideneglycerol, 1.2 - mono - (m - methylbenzylidene) glycerol and 2.4 - mono - (m - methylbenzylidene) sorbitol are specifically disclosed.
Description
SPECIFICATION
Anti-tumor agent
This invention relates to anti-tumor agents.
Hitherto, a wide variety of compounds have been used as anti-tumor agents, but most of these con ventional anti-tumor agents are not satisfactory with respect to their anti-tumor effects, side-effects and so on, and development of excellent anti-tumor agents has long been demanded for many years.
Recently, benzaldehyde has been proposed as an anti-tumor agents having a specific activity, as disclosed in Japanese Patent Publication No. 962/79, but benzaldehyde has disadvantages in that it is liable to be oxidized, thereby giving rise to various difficulties in producing pharmaceutical preparations containing benzaldehyde.
As a result of extensive studies on the development of novel anti-tumor agents, it has now been found that certain benzylidene compounds of certain polyalcohols have an excellent anti-tumor activity.
More particularly, anti-tumor agents according to the invention comprise, as an active ingredient, at least one compound represented by the formula (I)
wherein each of X1, the X2(s), and X3 independently represent hydrogen or a single chemical bond, provided that at least two of X', the X2(s), and X3 represent single chemical bonds, R represents hydrogen or an alkyl group, m is an integer of from 1 to 4, and n is an integer of from 1 to 3.
The compounds represented by the formula (I) have been used as gelatinizer of various organic liquids, for example, they have been used for producing solid toiletries, adhesives, solid alcohol fuels and the like and also as a thickener for paints, inks, polymers and the like, but they have not yet been reported as having pharmacological activities, and are not known to have been practically utilized as pharmaceutical agents.
According to this invention, it has been unexpectedly found that the compounds of the formula (I) exhibit excellent inhibitory activity on tumors induced by carcinoma transplanted subcutaneously into mammals, which are well recognized as a model of transplanted tumor, have low toxicity and are useful as an antitumor agent in mammals such as human and animals.
This invention is based on the above finding of antitumor activity, and provides an antitumor agent comprising, as an active ingredient, at least one compound represented by the formula (I)
wherein each of X', the X2(s), and X3 independently represent hydrogen or a single chemical bond (that is, X', X2 and X3 need not be identical, nor all of the
X2s in a particular compound required to be identical), provided that at least two of X', the X2(s), and X3 represent single chemical bonds, R represents hydrogen or an alkyl group having from 1 to 6 carbon atoms, m is an integer of from 1 to 4 and n is an integer of from 1 to 3.
The term "alkyl" as used herein forthe substituent
R refers to a straight or branched chain alkyl group having from 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl groups, and so forth.
R is preferably hydrogen our a lower alkyl group having 1 to 4 carbon atoms, and most preferably is a methyl group.
The compound represented by the formula (I) above can be prepared by a conventional procedure comprising reacting a sugar alcohol represented by the formula (II)
wherein m is as defined above, with a benzaldehyde represented bytheformula (Ill)
wherein R is as defined above, as disclosed in
Japanese Patent Publication Nos. 43748/73 and 14758/74 and in the Journal of the American Chemical Society, Vol. 50, p.2237 (1928).
The reaction between the sugar alcohol (il) and the aldehyde (III) can be achieved by, for example, dehydration reaction using about 1 td about3 mols of a benzaldehyde per mol of a sugar alcohol or by reaction between an aqueous solution of a sugar alcohol with a benzaldehyde in a molar ratio of about 1 to about 3 mols of a benzaldehyde per mol of a sugar alcohol in the presence of cyclohexane and a saturated hydrocarbon having 6 to 10 carbon atoms at a temperature of from room temperature to about 80"C for a period of about 5 to about 10 hours, as disclosed in Japanese Patent Publication Nos.
43748/73 and 14758/73.
Examples of sugar alcohols represented by the formula (II) include triose, tetrose, pentose and hexose which can be D-form, L-form or meso form and include sorbitol, mannitol, iditol, talitol, dulcitol, allitol, arabitol, xylitol, adonitol, erythritol, glycerin, and the like.
Examples of benzaldehydes represented by the formula (III) include benzaldehyde, tolualdehyde, ethylbenzaldehyde, propylbenzaldehyde, butylbenzaldehyde, pentylbenzaldehyde, hexylbenzaldehyde, and the like, with benzaldehyde ortolualdehyde being preferred.
The compound of formula (I) is a condensation product of one mol of a trihydric to hexahydric sugar alcohol represented by the formula (II) and 1 to 3 mols of a benzaldehyde represented by the formula (III), provided that at least two of X', the X2s and X3 represent single chemical bonds to a benzlidene group ofthe formula (Illa)
wherein R is as defined above. The above benzylidene group (Illa) is generally bonded in a bridge form to the hydroxy groups on the adjacent two carbon atoms or on the two carbon atoms separated by one intermediate carbon atom of the sugar alcohol, as illustrated below.
The relationship between the symbols "m" and "n" in the formula (I) is, therefore, n = 1 when m = 1; n = 1 or2 when n = 2 and 3; and n = 1,2 or3 when m = 4.
Typical examples of the compounds of the formula (I) are shown below, but the present invention is not limited to these specific compounds.
2 -4 - Monobenzylidenesorbitol
1 .3, 2 -4 - Dibenzylidenesorbitol
3, 2 4, 5 6 -Tribenzylidlenesorbitol
1 -3,2 .4, Dibenzylidenexylitol
1 2 - Monobenzylideneglycerol
1 -2 - Mono - (m - methylbenzylidene) - glycerol
2 .4 - Mono - (m -methylbenzylidene) - sorbitol
As described above, the compounds of the formula (I) have an excellent anti-tumor activity.
Although the exact mechanism of the activity of these compounds are not clearly understood, it is believed that these compounds are hydrolyzed easily in an acidic solution at a pH below about4 into the compound of the formula (III), i.e., benzaldehyde or an alkyl-substituted benzaldehyde and the sugar alcohol of the formula (II), e.g., sorbitol, xylitol, glycerin, etc., which corresponds to the sugar alcohol moiety of the compound (I), and the thusproduced compound (III) exhibits the desired antitumor activity.
The compounds of formula (I) can be used peruse as an anti-tumor agent, solely or in a mixture of two or more compounds, but generally these compounds are preferably formulated into pharmaceutical preparations suitable for oral or parenteral administration, together with known organic or inorganic, solid or liquid excipients, auxiliary agents, inclusion agents, and the like.
Suitable examples of excipients are, for example, water, gelatin, lactoset,starch, cellulose calcium glycolate, fine crystalline cellulose, stearyl alcohol, magnesium stearate, talc, vegetable oils, benzyl alcohol, propylene glycol, gums, polyalkylene glycols, white petrolatum, jelly, cholesterol and the like.
Suitable examples of auxiliary agents are, for example, preservatives, humectants (wetting agents), emulsifiers, solubilizing or disintegrating agents, osmotic pressure adjusting salines, buffering agents, birtders, suspending or dispersing agents and the like.
Suitable examples of inclusion agents are, for example, cyclodextrin and the like.
Examples of pharmaceutical preparation forms
include, for example, powders, granules, capsules,
pills, tablets, sugar-coated tablets, injections, sup
positories, ointments and the like, and preferably are
dosage forms suitable for oral administration. These
preparations can be prepared by conventional pro
cedures well known in the art.
In a method using the anti-tumor agent of the present invention for the treatment of tumor, the antitumor agent can be administered at the dose of 0.5 to 6,000 mg per day, based on the amount of active ingredient in human adult, in a single dose or multiple doses.
The anti-tumor agent can also be used in mammals and the dose level can be suitably adjusted based on the body weight of the animal to be treated. Preferred dose levels are from about 0.01 to about 120 mg per kg of the body weight per day.
The present invention is further illustrated by the following-Synthesis Examples (Preparation of Compounds), Example and Test Example. Unless otherwise indicated, all parts, percents, ratios and the like are by weight.
SYNTHESIS EXAMPLE 1 64 g of a 70% aqueous sorbitol solution, 53 g of benzaldehyde and 6 g of 50% sulfuric acid were charged in a 11 four-necked flask equipped with a condenser having a decanter, a thermometer, a gas inlet and a stirrer, and 500 ml of a mixture of cyclohexane and dimethyl sulfoxide (100 3 by volume) was added to the flask. After substituting the system with nitrogen gas, the mixture was allowed to react at 70 to 80"C with stirring while distilling off water in the mixture and water formed by condensation as an azeotropic mixture with cyclohexane by the decanter.
After 3 hours' reaction, a mixture of 2 .4 4 - monobenzylidenesorbitol and 1 .3, x,2 4- -4-diben- zylidenesorbitol (about 1:1) was produced. A solution of 5.1 g of potassium hydroxide dissolved in 100 ml of water was added to the mixture and the resulting mixture was stirred at room temperature for 1.5 hours to render the mixture neutral. Then, 100 ml of water was added thereto, followed by heat- refluxing thereby transferring mono benzylidenesorbitol to the aqueous layer. The uppercyclohexane layerwas separated from the lower aqueous layer, and the aqueous layer was allowed to cool to room temperature to precipitate monobenzyl idenesorbitol. The precipitate was filtered, washed with methanol and dried to obtain 32 g of 2 .4- 4 - monobenzylidenesor- bitol.
Melting Point: 270-271 C Elementary Analysis:
Found (%): C, 57.80; H, 6.86
Calcd. (%): C, 57.77; H, 6.71 On the other hand, 500 ml of water was added to the cyclohexane layer obtained above the cyclohexane was recovered by heat-distillation, leaving an aqueous slurry containing dibenzylidenesorbitol.
The slurry was separated by centrifugation, washed with water and dried to obtain 36 g of 1 3, 2 .4 4 - dibenzylidenesorbitol.
Melting Point: 226.5 - 227.5 C Elementary Analysis:
Found (%): C, 67.12; H, 6.32
Calcd. (%): C,67.03; H,6.19
SYNTHESIS EXAMPLE 2
The reaction was conducted in the same manner as described in Synthesis Example 1 but using 35 g of a 70% aqueous sorbitol solution, 43 g of benzaldehyde, 0.47 g of concentrated sulfuric acid and 526 ml of cyclohexane and reacting for about 7.5 hours to obtain 51.2 g of 1 -3,2-4,5 3,2 2 4, 5 5 6 -6-triben- zylidenesorbitol.
Melting Point: 203-204"C Elementary Analysis:
Found (%): C,72.43; H, 5.80
Calcd. (%): C, 72.48; H, 5.82
SYNTHESIS EXAMPLE 3
The reaction was conducted in the same manner as described in Synthesis Example 1 but using 151 g of a xylitol powder, 212 g of benzaldehyde, 3 g of 50% sulfuric acid and 1.3 l of a mixture of cyclohexane and dimethylformamide (100:3 by volume) and reactingforshourstoobtain290gofl .3, 2 4- dibenzylidenexylitol.
Melting Point: 187-188"C Elementary Analysis:
Found (%): C, 69.75; H, 5.79
Calcd. (%): C, 69.72; H, 5.81
SYNTHESIS EXAMPLE 4
The reaction was conducted in the same manner as described in Synthesis Example 1 but using 92 g of glycerin, l20gofm-tolualdehyde, 1 gof p-toluenesulfonic acid and 200 ml of toluene and reacting for4 hours at 20"Cto obtain 120 g of 1 2 mono - (m - methylbenzylidene) glycerol.
Boiling Point: 133-134"C/2 mmHg
SYNTHESIS EXAMPLE 5
The reaction was conducted in the same manner as described in Synthesis Example 4 but using 106 g of benzaldehyde instead of m - tolualdehyde to obtain 111 g of 1 -2 - monobenzylideneglycerol.
Boiling Point: 130-132"C/2 mmHg
SYNTHESIS EXAMPLE 6
The reaction was conducted in the same manner as described in Synthesis Example 1 but using m tolualdehyde instead of benzaldehyde to obtain 2 4 - mono - (m - methylbenzylidene) sorbitol.
Melting Point: 148-150"C Elementary Analysis:
Found (%): C, 59.13; H,7.10
Calcd. (%): C, 59.15; H, 7.04 EXAMPLE
Preparation of Tablets
2,500 g of a compound of the formula (1), 1,375 g of lactose, 775 g of fine crystalline cellulose and 375 g of calcium cellulose glycoate were passed through a 16-mesh sieve (JIS standard) and blended uniformly.
The mixture was charged into a blender and 31 of a 3% hydroxypropyl cellulose solution in a mixture of isopropyl alcohol and water (3 : 7 by volume) was added thereto, followed by blending. The mixture was extruded through a granulatorto obtain granules which were then dried at 40"C for 8 hours in an air stream. The granular size was regulated in the range of from 16 to 60 mesh (JIS standard) and magnesium stearate was added to the granules in an amount of 0.3% relative to the granules. The mixture was then compressed by a tabletting machine to produce 200 mg tablets, each containing 100 mg of the compound of the formula (I) as an active ingredient.
TEST EXAMPLE
Anti-TumorActivity
Ehrlich carcinoma ascites cells were transplanted subcutaneously to 5-week old ICR/JCL male mice (10 mice per group) in an amount of 2 x 106 cells per mouse. Each of the test compounds shown in Table 1 below was then administered orally as a single dose from the next day of the transplantation of tumor cells for 24 consecutive days. The test compounds were administered in the form of solutions dissolved in a physiological saline solution adjusted to a predetermined concentration of the test compound in such a manner than the liquid volume administered is 0.2 ml per mouse. On the 25th day from the transplantation, the tumor was excised from each of the mice and weighed, and the % inhibition of tumor was calculated by the following equation.
Tumor Weight in Tumor Weight in % Inhibition = Non-Medication Group Medication Group, 100
TumorWeightin Non-Medication Group
The results obtained by the above test are shown in Table 1 below.
TABLE I
Test Compounds Dose Inhibition
(mg/kg/day) (%) 2 - 4 - Monobenzylidene - 24 31.7 sorbitol
120 14.6 1 3,2-4-Dibenzylidene- 16 18.4 sorbitol
80 16.2 1 -3, 2 -4, 4, 5 6 - 14 20.7
Tribenzylidenesorbitol
70 23.3 1 -3, 2 -4-Dibenzylidene- 15 19.8 xylitol
80 27.5 1 - 2-Monobenzylidene- 17 0.0 glycerol
85 28.3 1 -2-Mono-(m.methyl- 18 13.4 benzylidene) glycerol
90 26.1 2-4-Mono-(m-methyl-(m-methyl- 28 4.3 benzylidene) sorbitol
135 20.5
The above results clearly indicate that the compounds of the present invention having the formula (I) are effective as anti-tumor agents.
While the invention has been described in detail and with reference to specific embodiments thereof, it will be apparent to one skilled in the artthat various changes and modifications can be made therein without departing from the spirit and scope thereof.
Claims (8)
1. An anti-tumor agent comprising, as an active ingredient, at least one compound represented by the formula (I)
wherein each of X', the X2(s), and X3 independently represent hydrogen ora single chemical bond, provided that at least two of X1, theX2(s), and X3 represent single chemical bonds, R represents hydrogen or an alkyl group having from 1 to 6 carbon atoms, m is an integer of from 1 to 4, and. n is an integer of from 1 to3.
2. An anti-tumor as claimed in claim 1,wherein R represents hydrogen or an alkyl group having from 1 to 4 carbon atoms.
3. An anti-tumor agent as claimed in claim 1, wherein R represents a methyl group.
4. An anti-tumor agent as claimed in claim 1, wherein said compound is selected from 2.4 monobenzylidenesorbitol, 1.3,2.4 dibenylidenesorbitol, 1.3,2.4, 5.6 -triben zylidenesorbitol, 1.3, 2.4 - dibenzylidenexylitol, 2.2 monobenzylideneglycerol, 1.2 - mono - (m - methylbenzylidene) glycerol and 2.4 - mono - (m - methylbenzylidene) sorbitol.
5. An anti-tumor agent as claimed in claim 1, when produced by the method described in any one of Synthesis Examples 1 to 6.
6. A pharmaceutical composition for the treatment of tumors comprising an anti-tumor agent as claimed in any preceding claim, and a pharmaceuti cally acceptable excipient.
7. The use of at least one compound as defined in any one of claims 1 to 5 in a method of treatment of tumors.
8. A unit dosage comprising 0.01 to 120 mg per kg of body weight per day of at least one compound as defined in any one of claims 1 to 5.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP8390079A JPS568315A (en) | 1979-07-04 | 1979-07-04 | Antitumor agent |
Publications (2)
Publication Number | Publication Date |
---|---|
GB2055576A true GB2055576A (en) | 1981-03-11 |
GB2055576B GB2055576B (en) | 1983-09-14 |
Family
ID=13815497
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB8021580A Expired GB2055576B (en) | 1979-07-04 | 1980-07-01 | Anti-tumour agent |
Country Status (4)
Country | Link |
---|---|
JP (1) | JPS568315A (en) |
DE (1) | DE3025057A1 (en) |
FR (1) | FR2460673A1 (en) |
GB (1) | GB2055576B (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0945452A1 (en) * | 1996-11-28 | 1999-09-29 | New Japan Chemical Co.,Ltd. | Sugar compounds, gelling agents, gelling agent compositions, processes for the preparation of them, and gel compositions |
US6846944B2 (en) | 2002-08-08 | 2005-01-25 | Crompton Gmbh | Process for preparing monoalkyltin halides and dialkyltin halides and their use |
CN111961027A (en) * | 2020-08-18 | 2020-11-20 | 上海齐润化工有限公司 | Composition and method for preparing transparent articles under low temperature conditions |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2519161A1 (en) * | 1975-04-30 | 1976-11-18 | Henkel & Cie Gmbh | ANTI-INFLAMMATORS FOR COSMETIC PREPARATIONS |
-
1979
- 1979-07-04 JP JP8390079A patent/JPS568315A/en active Granted
-
1980
- 1980-07-01 GB GB8021580A patent/GB2055576B/en not_active Expired
- 1980-07-02 DE DE19803025057 patent/DE3025057A1/en active Granted
- 1980-07-03 FR FR8014836A patent/FR2460673A1/en active Granted
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0945452A1 (en) * | 1996-11-28 | 1999-09-29 | New Japan Chemical Co.,Ltd. | Sugar compounds, gelling agents, gelling agent compositions, processes for the preparation of them, and gel compositions |
EP0945452A4 (en) * | 1996-11-28 | 2002-06-05 | New Japan Chem Co Ltd | Sugar compounds, gelling agents, gelling agent compositions, processes for the preparation of them, and gel compositions |
US6846944B2 (en) | 2002-08-08 | 2005-01-25 | Crompton Gmbh | Process for preparing monoalkyltin halides and dialkyltin halides and their use |
CN111961027A (en) * | 2020-08-18 | 2020-11-20 | 上海齐润化工有限公司 | Composition and method for preparing transparent articles under low temperature conditions |
CN111961027B (en) * | 2020-08-18 | 2023-11-17 | 上海齐润新材料有限公司 | Composition and method for preparing transparent articles at low temperature |
Also Published As
Publication number | Publication date |
---|---|
DE3025057A1 (en) | 1981-01-22 |
FR2460673B1 (en) | 1985-04-19 |
DE3025057C2 (en) | 1990-09-06 |
JPS568315A (en) | 1981-01-28 |
FR2460673A1 (en) | 1981-01-30 |
GB2055576B (en) | 1983-09-14 |
JPH0120129B2 (en) | 1989-04-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
FI92388C (en) | Process for Preparing Therapeutically Useful Cyclodextrin Clathrate of a Carbacycline Analog | |
US4564686A (en) | Phosphoric acid diesters or their salts and process for producing the same | |
EP0059158B1 (en) | Aza prostacyclins, their preparation and therapeutic applications | |
CA1270844A (en) | Quinone derivative and pharmaceutical composition containing the same | |
HU188840B (en) | Process for preparing glycerine derivatives and pharmaceutical compositions containing such compounds as active substances | |
US4452812A (en) | Organic complex of platinum, its preparation and its use for treating malignant tumors | |
HU189584B (en) | Process for preparing 5-substituted-picolinic acid-tocopherol esters and pharmaceutical compositons containing such compounds | |
GB2055576A (en) | Anti-tumor agent | |
US5250735A (en) | 2-(N-substituted-aminoalkyl)-5-(E)-alkylidene cyclopentanones, 2-(N-substituted-aminoalkyl)-5-(E)-arylalkylidene cyclopentanones, and derivatives thereof | |
JPH01113391A (en) | Mitomycin derivative | |
FI66607B (en) | FREQUENCY REQUIREMENT FOR THERAPEUTIC THERAPEUTIC EQUIPMENT 1,2-5,6-DIANHYDRO-HEXITOLER | |
US4130648A (en) | 5-Fluorouracil derivatives and antitumor preparations containing the same | |
JP3110500B2 (en) | Hypoglycemic inhibitor | |
US4310521A (en) | Aspirin-isopropylantipyrine | |
WO1985001729A1 (en) | 5-fluorouracil derivatives and medicinal preparation containing same | |
JPS609022B2 (en) | Indirubin derivatives and antitumor agents containing them | |
JPH0228189A (en) | Ascorbic acid phosphoric acid ester derivative and production thereof | |
EP0192317B1 (en) | Homocarnosine or acylhomocarnosine salts | |
US4906669A (en) | Isoprenoid derivatives and anti-ulcer agents containing the same | |
Wyrick et al. | Effects of molecular modification on hypocholesteremic activity of 1, 3-bis (substituted phenoxy)-2-propanones and related derivatives | |
JPH06505732A (en) | Novel phenol ethers, their production methods and drugs containing them | |
AU621430B2 (en) | Aroyloxy alkanols as anti-retrovirus agents | |
FR2541994A1 (en) | NOVEL PHENYLACETIC ESTER DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THERAPEUTIC USE THEREOF | |
JP2512304B2 (en) | Novel glycerin derivative and antihypertensive agent | |
JP2737240B2 (en) | Novel platinum complex and tumor therapeutic composition |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PCNP | Patent ceased through non-payment of renewal fee |