WO1997003996A1 - DERIVES DE GLUCOSIDE C DE LEWIS X/a - Google Patents

DERIVES DE GLUCOSIDE C DE LEWIS X/a Download PDF

Info

Publication number
WO1997003996A1
WO1997003996A1 PCT/JP1996/001964 JP9601964W WO9703996A1 WO 1997003996 A1 WO1997003996 A1 WO 1997003996A1 JP 9601964 W JP9601964 W JP 9601964W WO 9703996 A1 WO9703996 A1 WO 9703996A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
reaction
compound
fucopyranosyl
mmol
Prior art date
Application number
PCT/JP1996/001964
Other languages
English (en)
Japanese (ja)
Inventor
Masaji Hayashi
Naonori Imazaki
Original Assignee
Sumitomo Pharmaceuticals Company, Limited
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Sumitomo Pharmaceuticals Company, Limited filed Critical Sumitomo Pharmaceuticals Company, Limited
Publication of WO1997003996A1 publication Critical patent/WO1997003996A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms

Definitions

  • the present invention relates to derivatives of Lewis X and Lewis a sugar chains known as causative substances such as inflammation, blood reperfusion injury, autoimmune disease and cancer metastasis, that is, Lewis x / a-C-glycoside derivatives It is.
  • Such a derivative has cell adhesion inhibitory activity and is useful as a medicament for treating and improving these diseases.
  • E-selectin a neutrophil adhesion molecule expressed on vascular endothelial cells
  • P-selectin a neutrophil adhesion molecule expressed on vascular endothelial cells and platelets
  • L-selectin a homing receptor for lymphocytes
  • Lewis x It is known to recognize sugar chain structures such as Caryl Lewis X and Caryl Lewis a as ligands (Shigeaki Morooka, History of Medicine, Dish, 108 (1994)). For example, since the onset of various inflammatory diseases starts from the interaction through the binding of these selectins to ligands, it is anticipated that substances that inhibit such adhesion may become anti-inflammatory drugs. ( ⁇ ⁇ P.
  • An object of the present invention is to provide chemically and physiologically more stable Lewis x / a-C-glycoside derivatives, pharmaceutical compositions containing the same as an active ingredient, and uses thereof.
  • FIG. 2 shows the adhesion inhibitory activity of the compound of the present invention at several concentrations.
  • Adhesion inhibitory activity the value in Ueru containing no sample as a 1 100% (Control) showed the degree of inhibition at 0/0.
  • Ri is a Ci-Cis alkyl group or a phenyl Ci-C 12 alkyl group.
  • R2 is a hydrogen atom, a hydroxyl group or an acylamino group represented by the formula NHCOX.
  • X is a d-Cs alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aromatic heterocyclic group, or a C Ce having an aryl or aromatic heterocyclic group at its terminal. It is an alkyl group.
  • the Ci-C alkyl group in Ri in the above formula is a straight-chain or branched alkyl group having 1 to 18 carbon atoms, specifically, a methyl group, an ethyl group, and an n-propyl group.
  • the aromatic heterocyclic group for X is a 5-membered monocyclic or 6-membered monocyclic ring containing one or two oxygen atoms, sulfur atoms or nitrogen atoms, or a condensed polycyclic ring formed by condensing a 6-membered ring and a 5-membered ring.
  • Cyclic or 6-membered ring condensed Represents a polycyclic aromatic heterocyclic group.
  • a furyl group for example, a furyl group, a chenyl group, a pyridyl group, a virazinyl group, a benzo [b] furanyl group, a benzo [ c ] furanyl group, a benzo [b] chenyl group, a benzo [c] chenyl group, a pyrimidinyl group, a pyridazinyl group Quinolinyl group, isoquinolinyl group, quinoxalinyl group, naphthyridinyl group, phthalazinyl group, quinazolinyl group and the like.
  • the position of the bonding branch in forming the group can be arbitrarily selected from all possible positions.
  • CiC 6 alkyl group having an aryl group at the terminal of X is, for example, a phenyl (: 1- (: 6 alkyl group, that is, a carbon atom having a terminal phenyl group having 1 carbon atom).
  • It is a linear or branched alkyl group consisting of up to six, and specific examples include a benzyl group, a phenethyl group, a phenylpropyl group, and a phenylbutyl group.
  • the d-Cs alkyl group having an aromatic heterocyclic group at the terminal of X is a linear or branched alkyl group having 1 to 6 carbon atoms and having an aromatic heterocyclic group at the terminal.
  • R 13 , R "and R are a d-Ce alkanoyl group or an aryl group.
  • R is a hydrogen atom, an acylamino group, a phthalimid group or a hydroxyl group represented by the formula NHC0X.
  • the reaction is preferably performed in a solvent.
  • the solvent to be used include ether solvents such as getyl ether, tetrahydrofuran, dimethyloxetane, and dioxane; halogen solvents such as methylene chloride, 1,2-dichloroethane; benzene; Aromatic solvents such as toluene and benzene, aliphatic hydrocarbon solvents such as hexane and cyclohexane, dimethylformamide (DMF), dimethylacetamide, acetonitrile, propionitrile , Polar aprotic solvents such as nitromethane, nitroethane and nitropropane, or acetone. These may be used alone or as a mixed solvent.
  • ether solvents such as getyl ether, tetrahydrofuran, dimethyloxetane, and dioxane
  • halogen solvents such as methylene chloride, 1,2-dichlor
  • the phenyl C 2 -Ci 2 alkenyl group for R 5 is a linear or branched alkenyl group having 2 to 12 carbon atoms and having a phenyl group at a terminal, specifically, a phenylvinyl group. And 3-phenylaryl groups.
  • the C 2 -Ci 8 alkynyl group for R 5 is a linear or branched alkynyl group having 2 to 18 carbon atoms, specifically, an ethylyl group, a 1-propylyl group and the like. No.
  • Compound (10) of the present invention can be produced from compound (2) by the method described below.
  • R1 9 of the compound (13) is a Futaruimi de group prior to the B- 4 step, by performing Ashiru of Amino groups obtained was deprotected Futaruimi de group, wherein NHCOX (X Is preferably the same as described above).
  • R 5 is an alkyl group
  • deprotection can be carried out using cerium ammonium nitrate (CAN) or dichlorodicyanoquinone (DDQ) in the same manner as in step A-4, for example. 14) can be obtained.
  • CAN cerium ammonium nitrate
  • DDQ dichlorodicyanoquinone
  • the compound (15) can be produced by protecting the hydroxyl group of the compound (14) obtained above, if necessary, in the same manner as in Step A-5.
  • Compound (10) of the present invention can be produced by hydrolyzing compound (15) obtained above in a solvent under basic conditions in the same manner as in Step A-5.
  • a compound in which R 3 is a D-galactopyranosyl group and R 4 is a hydrogen atom can also be produced from compound (2) by the same method as in Scheme B described above. it can. However, in order to produce such a compound, it is desirable to omit step B-3 and carry out steps B-4, B-5 and B-6.
  • R 3 is a hydrogen atom
  • R 4 is a L-fucoviranosyl group.
  • the protecting group to be introduced onto the hydroxyl group is preferably a d-Cs alkanoyl group, an arylo group, a benzyl group or a substituted benzyl group, and these can be introduced by the same method as in Step B-5.
  • R2, R5 and R18 have the same meaning as described above.
  • R16 is protected represented by hydrogen atom, Ashiruamino group of the formula NHCOX, Futaruimi de group, or a group of the formula OR 17, Hydroxyl group.
  • X in the formula NHCOX has the same meaning as described above.
  • Ri is d-Ce alkanoyl, aryloyl, benzyl or substituted benzyl.
  • Z 3 is a leaving group.
  • a C-glycosidation product (17) By reacting the compound (16) having a leaving group Z 3 with a carbon nucleophile in the presence of a Lewis acid or a metal salt, a C-glycosidation product (17) can be produced. .
  • Fuenirusuru phenyl group such as a dialkyl phosphoryl group or Jifue sulfonyl phosphonyl group, may be mentioned as a leaving group Z 3 (Studies in Natural Products Chemistry , Vol.10, 337 ⁇ 403, Elsevier Science Publishers (1992), MHD Postema, Tetrahedron, Vol. 48. 8545-8599, (1992)).
  • the compound (16) having a leaving group Z3 used in this reaction is 3,4,6-tri-10-protected-12-dexoxyD-glucose, alkyl 3.4,6-tree 0-protected 2-Doxy-D-glycoside, 1-0-Acyl-3,4,6-tree 0-protected 2-Doxy-D-glucose, 2,3,4,6-tetra-0-Protected D-glycose, alkyl Using 2, 3, 4, 6-tetra-1-protected-D-glycoside, 110-acyl-1,2, 3.4.6-tetra-0-protected-D-glycose, using standard methods It can be manufactured (for example, see the 4th edition Experimental Chemistry Course, Vol. 26, Organic Synthesis VII, pp. 267 to 354, edited by The Chemical Society of Japan (1992)).
  • alkenyl silane compounds include s equipotent Arukeniruchin compound or Arukini Rumetaru compound.
  • the Lewis acid or metal salt used in the reaction includes trimethylsilyl trifluoromethanesulfonate (TMS triflate), silver triflate, tin triflate, methyl triflate, anhydrous triflate, trityl perchlorate, silicon tetrafluoride, trimethyl chloride Silane, trimethylsilane bromide, trimethylsilane iodide, ethereal boron trifluoride, zinc chloride, zinc bromide, zinc iodide, stannous chloride, stannous bromide, stannous iodide, chloride Stannic, stannic bromide, stannic iodide, titanium tetrachloride, titanium tetrabromide, titanium tetraiodide, ferric chloride, ferric bromide, ferric iodide, ferric chloride Copper, cupric bromide, aluminum chloride, aluminum bromide, aluminum iodide, mercuri
  • Ris of the compound (16) is an acylamino group or a phthalimid group
  • a radical initiator such as 2,2′-azobisisobutyronitrile is used instead of a Lewis acid or metal salt. It can also be used (see Imamura et al., Proceedings of the 69th Annual Meeting of the Chemical Society of Japan, 980, Kyoto, 1992).
  • the reaction is preferably carried out in a solvent.
  • solvent used examples include ether solvents such as getyl ether, tetrahydrofuran, dimethoxane, and dioxane; halogen solvents such as methylene chloride and 1,2-dichloroethane; benzene; Aromatic solvents such as toluene and benzene, aliphatic hydrocarbon solvents such as hexane and cyclohexane, dimethylformamide (DMF), dimethylacetamide, acetonitrile, propionitrile, Examples include polar aprotic solvents such as nitromethane, nitroethane, and nitropropane, and acetone. These may be used alone or as a mixed solvent.
  • ether solvents such as getyl ether, tetrahydrofuran, dimethoxane, and dioxane
  • halogen solvents such as methylene chloride and 1,2-dichloroethane
  • benzene Aromatic solvents
  • ⁇ , ⁇ , ', —' — tetramethylperyl pyridine, 2, 6-di-t-butylpyridine, 2, 6 —Lutidine, 2,4,6—collidine, triethylamine or molecular sieves (MS 3A, MS 4A or MS 5A) may coexist.
  • the reaction temperature is selected in the range from 170 to 100 t :, preferably from 120 to 60 (or the boiling point of the solvent).
  • the reaction time is generally 1 hour to 5 days, depending on the reaction temperature, the starting compounds used, the reagents, the solvent and the like.
  • R1? in the compound (17) obtained by the above method is a C Cs alkanoyl group or an aroyl group
  • the compound is hydrolyzed under basic conditions in a solvent.
  • compound (18) can be obtained.
  • the base examples include carbonates such as sodium carbonate and carbon dioxide; hydroxides such as sodium hydroxide and lithium hydroxide; bicarbonates such as sodium bicarbonate and bicarbonate; disodium hydrogen phosphate; Dipotassium hydrogen phosphate, or triethylamine, N, N-diisopropylethylamine, pyridine, dimethylaniline, 1,8-diazabicyclo [5.4.0] pendene (DBU), lithium hexamethyldisilazane, sodium methoxide
  • Organic bases such as sodium ethoxide and the like can be used.
  • R in the compound (17) is a benzyl group or a substituted benzyl group
  • the compound (18) can be obtained by hydrogenation in the presence of palladium carbon.
  • the amount of palladium carbon used may be a catalytic amount, and is usually 0.001 to 1 equivalent.
  • the hydrogen supply source include hydrogen molecule, formic acid, ammonium formate, cyclohexene, 1,4-cyclohexadiene, and cis-decalin.
  • Each reaction is preferably performed in a solvent, and examples of the solvent include those exemplified in the above-mentioned step A-4. These may be used alone or as a mixed solvent.
  • the reaction temperature is selected from the range of 70 to 100, preferably 0 to 60 (or the boiling point of the solvent).
  • the reaction time is mainly determined by the reaction temperature, the starting compound used, the reagent, the solvent, and the like, and is generally 1 hour to 2 days.
  • cyclic acetal-based protective reagents include benzaldehyde, benzaldehyde dimethyl acetal, benzaldehyde bis (trimethylsilyl) acetal, substituted benzaldehyde, substituted benzaldehyde dimethyl acetal or substituted benzaldehyde bis ( Trimethylsilyl) acetal, etc. o
  • Examples of the acid catalyst include sulfuric acid, paratoluenesulfonic acid, camphorsulfonic acid and the like.
  • the reaction is preferably carried out in a solvent.
  • the solvent include those exemplified in the above-mentioned step A-1.
  • DMF dimethylformamide
  • dimethylacetamide dimethylacetamide
  • acetonitrile acetonitrile
  • propionitrile nitromethane
  • polar aprotic solvents such as nitroethane, nitropropane and the like. These are used alone or as a mixed solvent.
  • Orthoester or molecular sieves may coexist in the reaction system as a trapping agent for the water generated in the reaction system.
  • the reaction temperature is selected in the range of 170 to 100, preferably 0 to 60 (or the boiling point of the solvent).
  • the reaction time depends mainly on the reaction temperature, the starting compounds used, the reagents, the solvent and the like, but is usually from 1 hour to 2 days.
  • the pharmaceutical compositions of the present invention can block or inhibit the attachment of cells associated with many diseases.
  • a number of inflammatory diseases are associated with selectins expressed on vascular endothelial cells and platelets, and can be treated with the pharmaceutical compositions of the present invention.
  • the term “inflammation” refers to both specific and non-specific It means the response of the defense system.
  • the response of the specific defense system is the response of the specific immune system to the antigen.
  • specific defense system responses include the response of an antibody to an antigen, such as a virus, and delayed type hypersensitivity.
  • a non-specific defense system response is a leukocyte-mediated inflammatory response that is generally not possible for immunological storage.
  • Such cells include macrophages, eosinophils and neutrophils.
  • non-specific reactions include swelling immediately after bee stings, recruitment of PMN leukocytes at the site of bacterial infection (eg, lung infiltration in bacterial pneumonia and tumor formation in tumors).
  • Other treatable diseases include the following: For example, rheumatoid arthritis, leukocyte-mediated tissue damage after ischemia (reperfusion injury), frostbite injury or shock, acute leukocyte-mediated lung injury, (eg, adult dyspnea syndrome), asthma, traumatic shock, Treat also septic shock, nephritis, acute and chronic inflammation, atopic dermatitis, psoriasis, inflammatory bowel disease, various platelet-mediated pathological events, allergic atherosclerosis and coagulation Can be.
  • tumor metastasis can be inhibited or prevented by inhibiting the attachment of circulating cancer cells. Examples include colon cancer and melanoma.
  • PTCC percutaneous coronary thrombolysis
  • PTCR percutaneous coronary thrombolysis
  • the dose of the compound may be, for example, a specific compound, an administration method, a specific disease to be treated and its degree, and a patient. It will usually vary according to the overall health and condition of the patient and the prescribing physician. For example, dosages used for treatment of reperfusion injury range from about 50 g to 2,000 mg per day for a 70 kg patient. Ideally, therapeutic dosing should begin as soon as possible after a myocardial infarction or other injury.
  • the pharmaceutical composition of the present invention is administered parenterally, topically, orally, or transdermally. These pharmaceutical compositions are administered for prophylactic and / or therapeutic treatments. These pharmaceutical compositions can be administered in various unit dosage forms depending on the method of administration. For example, unit dosage forms suitable for oral administration include powders, tablets, pills, capsules and sugars. Suitable unit dosage forms for topical administration include, for example, aerosols.
  • compositions of the present invention are administered intravenously.
  • Compositions for intravenous administration consist of a solution of the compound of the present invention dissolved or suspended in a pharmaceutically acceptable carrier, preferably an aqueous carrier.
  • a pharmaceutically acceptable carrier for example, water, buffered water, 0.4% physiological food and the like can be used.
  • aqueous carrier for example, water, buffered water, 0.4% physiological food and the like can be used.
  • These compositions can be sterilized by conventional, well-known sterilization techniques, or can be sterile filtered.
  • the resulting aqueous solutions can be packaged as is, or lyophilized, the lyophilized preparation being combined with a sterile aqueous solution prior to administration.
  • the composition may contain any pharmaceutically acceptable adjuvants, such as pH and buffering agents, tonicity adjusting agents, wetting agents, etc., as required for the approximate physiological condition, e.g., sodium acetate, lactic acid It can contain sodium, sodium chloride, potassium chloride, calcium chloride, sorbitan monolaurate, teriethanolamine oleate, etc.
  • adjuvants such as pH and buffering agents, tonicity adjusting agents, wetting agents, etc.
  • compositions containing the compounds of the present invention are administered for prophylactic and / or therapeutic treatments.
  • the composition is administered to a patient already afflicted with the disease in an amount sufficient to cure or at least partially arrest the symptoms of the disease and its complications, as described above. You. Proper to achieve this! : Is defined as "therapeutically effective dose.”
  • the effective amount for this use will depend on the degree of illness and the weight and general condition of the patient, but will generally be 70 kg Of the compound of the present invention in a range of about 0.5 mg to about 2,000 m / day, preferably about 5 mg to about 500 mg / day of a patient weighing 70 kg. Use a dose in the mg range.
  • compositions containing the compounds of the present invention are administered to patients who are susceptible to, or otherwise at risk of, a particular disease.
  • the amount used in such cases is defined as a "prophylactically effective amount.”
  • the precise amounts will depend on the patient's state of health and weight, but generally, a patient weighing 70 kg will receive from about 0.5 m to about 1,000 mg of the compound of the invention per day. Range, and preferably, for a patient weighing 70 kg, a daily dose of the compound of the invention in the range of about 5 mg to about 500 mg.
  • compositions of this invention Upon administration of the compounds of this invention, single or multiple administrations of the compositions can be carried out, with the level and pattern of administration being selected by the treating physician.
  • the pharmaceutical formulation should provide a sufficient amount of the compound of the invention to effectively treat the patient.
  • the compounds of the present invention can also be used as diagnostic reagents.
  • labeled compounds can be used to locate areas of inflammation or tumor metastasis in patients suspected of having inflammation.
  • the compounds can be labeled with i 25 I, 14 c or tritium.
  • Example 1-2 The residue containing 1,2-dideoxy 1 ⁇ - (2-propinyl) -1-D-arabinohexopyranose (_2J (18.8 g of theory) obtained in Example 1-2 was purified with ⁇ , ⁇ -dimethylformamide. (100 ml), and add benzaldehyde dimethyl acetal (30.4 g) and (1S)-(+)-10-camphorsulfonic acid monohydrate (1.25 g), and at room temperature. After confirming the completion of the reaction, the reaction mixture was neutralized by adding triethylamine to the system and neutralized. The residue was washed with hexane and filtered, and the target compound 4 (17.7 g, 64.1 mmol) was added. 64.1%) was obtained as a white solid in three steps from the yield%.
  • 1,2-dideoxy-1-phthalimidido 1 /?-(2-propenyl) -1-D-glucopyranoside (26) (257 mg) was dissolved in acetonitrile (6 ml), and then benzaldehyde dimethyl acetal was dissolved. (0.22 ml, 1.47 mmol) and para-toluenesulfonic acid monohydrate (5 mg, 0.026 mmol) were added, and the mixture was stirred at room temperature. After 26 hours, paratoluenesulfonic acid monohydrate (18 mg, 0.095 mmol) was further added, and the mixture was stirred at room temperature for 7 hours.
  • the reaction mixture was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate, and then with saturated saline, dried over magnesium sulfate, filtered, and the filtrate was concentrated. Purification by silica gel column chromatography gave the target compound _Q_ (189 mg, 0.162 mmol, yield 68.4%).
  • the plate was placed in a plate washer to remove non-adherent HL-60 cells.
  • the settings of the plate washer were slow mode, cycle 3 (3 times washing), soak 0 sec. (Immersion time 0 seconds), 12 rows (plate lengthwise setting), and returned to room temperature for washing.
  • the dispensed volume of the NWB was 200 ul / ⁇ l at a time.
  • a citrate solution containing 0.1% NP-40 at room temperature was added at 50 ul / well, and left at room temperature for 5 minutes.
  • the substrate solution was used within 30 minutes after preparation.
  • the sources of experimental materials are as follows.
  • the compound of the present invention was adjusted to 100 mM with DPBS and the pH was adjusted to 7.1 to 7.4.
  • HL-60 was cultured in RPMI1640 medium supplemented with 10% fetal calf serum.
  • RPMI1640 medium was frozen using a cell freezing solution of 80% + 80 fetal serum 10 80 + DMS 10% at 1.5 ⁇ 107 cels per tube according to a conventional method, and stored at 1: 801. When used, they were used under sterile conditions.
  • composition of the DPBS / BSA solution is DPBS + 1% BSA.
  • the composition of NWB is HBSS + 10 mM HEPES + 0.2% glucose + 1% BSA + lm CaCl 2 *.
  • the citrate solution was prepared by dissolving 2.33 g of citrate and 9.20 g of Na 2 HP04.12-0.
  • the present invention (13), (23) and (35) inhibited adhesion of rsE-selectin to HL-60 by 50% or more at a concentration of 5 to 50 mM.
  • the Lewis x Za-C-glycoside derivative of the present invention has a cell adhesion inhibitory activity and is useful as a medicament for treating and improving inflammation, blood reperfusion injury, autoimmune disease or pain metastasis.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention se rapporte à des dérivés de glucoside C représentés par la formule générale (I), dans laquelle R1 représente alkyle C¿1-C18? ou phényle alkyle C1-12; R?2¿ représente hydrogène, hydroxy ou acylamino correspondant à la formule NHCOX (où X représente alkyle C¿1-6?, aryle éventuellement substitué, hétéroaryle éventuellement substitué ou alkyle C1-6 présentant aryle ou hétéroaryle à l'extrémité); et, lorsque R?2¿ représente hydrogène ou acylamino NHCOX, R3 et R4 diffèrent l'un de l'autre et représentent chacun D-galactopyranosyle, L-fucopyranosyle ou hydrogène; lorsque R2 représente hydroxy, R3 représente D-galactopyranosyle et R4 représente L-fucopyranosyle ou hydrogène, ou bien R3 représente L-fucopyranosyle et R4 représente D-galactopyranosyle ou hydrogène ou bien encore R3 représente hydrogène et R4 représente L-fucopyranosyle. Les composés considérés ont une activité inhibitrice de l'ahdésion cellulaire et constituent un médicament utile dans le traitement et la guérison d'affections telles que l'inflammation, des troubles de reflux circulatoire ischémiques, les maladies auto-immunes ou la métastase cancéreuse.
PCT/JP1996/001964 1995-07-18 1996-07-15 DERIVES DE GLUCOSIDE C DE LEWIS X/a WO1997003996A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP20541595 1995-07-18
JP7/205415 1995-07-18

Publications (1)

Publication Number Publication Date
WO1997003996A1 true WO1997003996A1 (fr) 1997-02-06

Family

ID=16506477

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1996/001964 WO1997003996A1 (fr) 1995-07-18 1996-07-15 DERIVES DE GLUCOSIDE C DE LEWIS X/a

Country Status (1)

Country Link
WO (1) WO1997003996A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108299525A (zh) * 2018-01-05 2018-07-20 佛山科学技术学院 路易斯寡糖-x的合成方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
J. AM. CHEM. SOC., (1994), Vol. 116, No. 26, MORTELL, K.H., "Synthesis of Cell Agglutination Inhibitors by Aqueous Ring-Opening Metathesis Polymerization", pages 12053-12054. *
TETRAHEDRON LETTERS, (1983), Vol. 24, No. 44, LANCELIN. J.M., "Synthesis and Conversions of C-(Alkyn-1-yl)-beta-D-Glucopyranosides", pages 4833-4836. *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108299525A (zh) * 2018-01-05 2018-07-20 佛山科学技术学院 路易斯寡糖-x的合成方法
CN108299525B (zh) * 2018-01-05 2021-03-26 佛山科学技术学院 路易斯寡糖-x的合成方法

Similar Documents

Publication Publication Date Title
US20220235087A1 (en) Mannose-derived antagonists of fimh useful for treating disease
JP3717512B2 (ja) 新規スフィンゴ糖脂質およびその使用
RU2392281C2 (ru) Сульфатированные производные олигосахаридов
US5763413A (en) Lewis-associated compound, process for producing the same, and anti-inflammatory
CA2493690C (fr) C-glycolipide de synthese et utilisation de celui-ci pour le traitement du cancer, des maladies infectieuses et des maladies auto-immunes
AU764106B2 (en) Purine derivatives
EA004987B1 (ru) Производные пурина
HUT74506A (en) Sialyl lewis-x analogues as inhibitors of cellular adhesion
US10738070B2 (en) Mannose-derived antagonists of FimH useful for treating disease
CZ20021223A3 (cs) Purinové deriváty
WO1996020204A1 (fr) Derive x de lewis et procede de production correspondant
JPH08208684A (ja) 細胞接着阻害剤としてのジカルボキシメチル化グリコリピド誘導体
EP3415522A1 (fr) Nouvel inhibiteur hybride de galactoside de galectines
CA3116515A1 (fr) Inhibiteurs alpha-d-galactoside de galectines
US5962660A (en) Sialyl Lewis X mimetics incorporating fucopeptides
CN108883122A (zh) 有用于治疗疾病的c-糖苷化合物
CA2551181A1 (fr) Composes mimetiques du glycosaminoglycane (gag)
WO1993023417A1 (fr) Nouveaux derives de l'adenosine
CN114555620A (zh) 半乳糖凝集素的新型半乳糖苷抑制剂
JP4233262B2 (ja) カルバ糖アミン誘導体及びそれを用いるグリコシダーゼ阻害剤
WO1997003996A1 (fr) DERIVES DE GLUCOSIDE C DE LEWIS X/a
TW200826947A (en) Method of producing anthracycline derivatives
JPH02115194A (ja) フッ素置換エピポドフィロトキシングルコシド類
KR20090074226A (ko) 혈액응고를 방해하는 화합물
Bajza et al. Chemical synthesis of the pyruvic acetal-containing trisaccharide unit of the species-specific glycopeptidolipid from Mycobacterium avium serovariant 8

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): CA MX US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA