EP1133512A2 - Benzylmaltoside als inhibitoren der proliferation von glatten muskelzellen - Google Patents

Benzylmaltoside als inhibitoren der proliferation von glatten muskelzellen

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Publication number
EP1133512A2
EP1133512A2 EP99960572A EP99960572A EP1133512A2 EP 1133512 A2 EP1133512 A2 EP 1133512A2 EP 99960572 A EP99960572 A EP 99960572A EP 99960572 A EP99960572 A EP 99960572A EP 1133512 A2 EP1133512 A2 EP 1133512A2
Authority
EP
European Patent Office
Prior art keywords
carbon atoms
hydrogen
alkyl
perfluoroalkyl
halogen
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.)
Withdrawn
Application number
EP99960572A
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English (en)
French (fr)
Inventor
Paul Jeffrey Dollings
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wyeth LLC
Original Assignee
American Home Products Corp
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 American Home Products Corp filed Critical American Home Products Corp
Publication of EP1133512A2 publication Critical patent/EP1133512A2/de
Withdrawn legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/18—Acyclic radicals, substituted by carbocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Definitions

  • This invention relates to the use of substituted benzylmaltosides as smooth muscle cell proliferation inhibitors and as therapeutic compositions for treating diseases and conditions which are characterized by excessive smooth muscle proliferation such as restenosis.
  • glycosaminoglycans heparin and heparan sulfate are endogenous inhibitors of SMC proliferation, yet are able to promote endothelial cell growth (Castellot, J.J. Jr.; Wright, T. C; Karnovsky, M.J. Seminars in Thrombosis and Hemostasis 1987, 13, 489).
  • heparin, heparin fragments, chemically modified heparin, low molecular weight heparins, and other heparin mimicking anionic polysaccharides may be compromised due to other pharmacological liabilities (excessive bleeding arising from anticoagulation effects, in particular) coupled with heterogeneity of the various preparations (Borman, S. Chemical and Engineering News, 1993, June 28, 27).
  • WO 96/14325 discloses acylated benzylglycosides as smooth muscle cell proliferation inhibitors.
  • the compounds of the present invention differ in that the substituents on the carbohydrate backbone are substantially different.
  • Patent numbers US 5,498,775, WO96/14324, and US 5,464,827 describe polyanionic benzylglycosides or cyclodextrins as smooth muscle cell proliferation inhibitors for treating diseases and conditions which are characterized by excessive smooth muscle proliferation, ⁇ -cyclodextrin tetradecasulfate has been described as a smooth muscle cell proliferation inhibitor and as an effective inhibitor of restenosis (Reilly, C.F.; Fujita, T.; McFall, R. C; Stabilito, I. I.; Wai-se E.; Johnson, R. G. Drug Development Research 1993, 29, 137).
  • US 5019562 discloses anionic derivatives of cyclodextrins for treating pathological conditions associated with undesirable cell or tissue growth.
  • WO 93/09790 discloses antiproliferative polyanionic derivatives of cyclodextrins bearing at least 2 anionic residues per carbohydrate residues.
  • Wetsberger (EP 312087 A2 and EP 312086 A2) describes the antithrombotic and anticoagulant properties of sulfated bis-aldonic acid amides.
  • US 4431637 discloses polysulfated phenolic glycosides as modulators of the complement system.
  • the compounds of the present invention differ from this prior art in that the compounds (a) are benzylmaltosides which bear no structural resemblance to heparin, sulfated cyclodextrins, or to sulfated lactobionic acid dimers, (b) contain no more than two contiguous sugar residues (disaccharide) and (c) are of a defined structure. DESCRIPTION OF THE INVENTION
  • This invention provides benzylmaltosides of formula I
  • Y is hydrogen, halogen, azido, or Het optionally substituted with R 10 ;
  • Het is l,3-dioxo-l,3-dihydro-isoindol-2-yl, imidazol-1-yl, or benzimidazol-1-yl;
  • R 1 , R 2 , R 3 and R 4 are each, independently, hydrogen, acyl of 2-7 carbon atoms, perfluoroacyl of 2-7 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, benzoyl, or benzyl;
  • R 5 is hydrogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, halogen, nitrile, nitro, alkoxy of 1-6 carbon atoms;
  • R 6 and R 7 are each, independently, hydrogen, acyl of 2-7 carbon atoms, perfluoroacyl of 2-7 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, alkylsulfonyl of 1-6 carbon atoms, perfluoroalkylsulfonyl of 1-6 carbon atoms, arylsulfonyl of 6-10 carbon
  • Alkyl, alkoxy, alkylsulfonyl, acylamino, alkoxycarbonyl and acyl includes both straight chain as well as branched moieties optionally substituted with fluorine.
  • Halogen means bromine, chlorine, fluorine, and iodine.
  • Aryl is defined as a fully unsaturated carbocyclic radical containing one or more rings having 6-10 carbon atoms optionally substituted with fluorine; with phenyl and naphthyl radicals being preferred.
  • salts can be formed from organic and inorganic acids, for example, acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, napthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly known acceptable acids.
  • Salts may also be formed from organic and inorganic bases, preferably alkali metal salts, for example, sodium, lithium, or potassium. Acid addition salts can be prepared when the compound of formula I contains a basic nitrogen, and base addition salts can typically be prepared when the compound of formula I contains a hydroxyl group.
  • the compounds of this invention may contain an asymmetric carbon atom and some of the compounds of this invention may contain one or more asymmetric centers and may thus give rise to optical isomers and diastereomers. While shown without respect to stereochemistry in Formula I, the present invention includes such optical isomers and diastereomers; as well as the racemic and resolved, enantiomerically pure R and S stereoisomers; as well as other mixtures of the R and S stereoisomers and pharmaceutically acceptable salts thereof.
  • Preferred compounds of this invention are benzylmaltosides of formula I
  • Y is hydrogen, halogen, azido, or Het optionally substituted with R 10 ; Het is l,3-dioxo-l,3-dihydro-isoindol-2-yl, or imidazol-1-yl;
  • R 1 , R 2 , R 3 and R 4 are each, independently, hydrogen, or acyl of 2-7 carbon atoms;
  • R 5 is hydrogen, alkyl of 1-6 carbon atoms, or halogen
  • R 6 and R 7 are each, independently, hydrogen, or acyl of 2-7 carbon atoms;
  • R 8 and R 9 are each, independently, hydrogen, or aryl of 6-10 carbon atoms;
  • R 10 is halogen, nitrile, nitro, amino, acylamino of 2-7 carbon atoms, carboxyl, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, or aryl of 6-10 carbon atoms; or a pharmaceutically acceptable salt thereof.
  • More preferred compounds of this invention are benzylmaltosides of formula I
  • Y is hydrogen, iodo, azido, or Het optionally substituted with R 10 ; Het is l,3-dioxo-lJ-dihydro-isoindol-2-yl, or imidazol-1-yl;
  • R 1 , R 2 , R 3 and R 4 are each, independently, hydrogen, or acetyl
  • R 5 is hydrogen, alkyl of 1-3 carbon atoms, or chloro
  • R s is hydrogen
  • R 7 is acetyl
  • R 8 is phenyl
  • R 9 is hydrogen
  • R 10 is nitro; or a pharmaceutically acceptable salt thereof.
  • Specifically preferred compounds of this invention are:
  • the compounds of this invention were be prepared according to the following schemes from commercially available starting materials or starting materials which can be prepared using literature procedures. This scheme shows the preparation of representative compounds of this invention.
  • Reduction of the nitro group of 3 can be accomplished with a reducing agent such as stannous chloride in a polar aprotic solvent such as such as ethyl acetate at ambient temperature to reflux or by catalytic hydrogenation in the presence of a catalyst such as palladium on carbon to give the anilino compound 4.
  • Coupling of 4 with an acid chloride can be completed in the presence of an amine base such as triethylamine, diisopropylethylamine or pyridine in an aprotic solvent such as dichloromethane or tetrahydrofuran at temperatures ranging from -20°C to ambient temperature to give the amide 5.
  • the acetate groups of 5 can be replaced by hydrolysis with a base such as sodium methoxide in methanol or aqueous sodium hydroxide in methanol at ambient temperature to reflux to yield 6.
  • a base such as sodium methoxide in methanol or aqueous sodium hydroxide in methanol at ambient temperature to reflux to yield 6.
  • the 4' and 6' groups can be reacted with an acetal in the presence of an acid catalyst such as camphorsulfonic acid or p-toluene sulfonic acid in a polar aprotic solvent such as N,N-dimethylformamide at temperatures ranging from 25°C to reflux to give the acetal/ketal derivative 7.
  • Selective tosylation at position 6 can be accomplished in the presence of a p- toluenesulfonyl chloride and an amine base such as triethylamine, diisopropylethylamine or pyridine in an aprotic solvent such as dichloromethane or tetrahydrofuran at temperatures ranging from -20°C to 5°C to give the tosylate 8 and reacylation with an acyl anhydride in the presence of an amine base such as pyridine at temperatures ranging from 0°C to ambient temperature to yield 9.
  • a p- toluenesulfonyl chloride and an amine base such as triethylamine, diisopropylethylamine or pyridine
  • an aprotic solvent such as dichloromethane or tetrahydrofuran
  • the tosylate 9 can be substituted with an appropriate nucleophile, which can be generated with a base such as sodium hydride or potassium carbonate in a polar aprotic solvent such as N,N-dimethylformamide at ambient temperature to give 10.
  • the acetate groups of 10 can be replaced by hydrolysis with a base such as sodium methoxide in methanol or aqueous sodium hydroxide in methanol at ambient temperature to reflux to yield 11.
  • the tosylate 8 can be substituted directly, without protection of hydroxyl groups, to yield 11.
  • the compounds of this invention are useful as antiproliferative agents. The following procedures show the evaluation of representative compounds of this invention in standard pharmacological test procedure which measured ability of the evaluated compound to inhibit smooth muscle cell proliferation
  • the compounds of this invention are useful in treating or inhibiting diseases which are characterized by excessive smooth muscle cell proliferation (smooth muscle cell hyperproliferation).
  • the compounds are particularly useful in treating hyperproliferative vascular diseases which are characterized by smooth muscle cell hyperproliferation, such as restenosis, which most frequently arises from vascular reconstructive surgery and transplantation, for example, balloon angioplasty, vascular graft surgery, coronary artery bypass surgery, and heart transplantation.
  • Other disease states in which there is unwanted "cellular" vascular proliferation include hypertension, asthma, and congestive heart failure.
  • the compounds of this invention are also useful as inhibitors of angiogenesis.
  • Angiogenesis neovascularization
  • the compounds of this invention are therefore useful as antineoplastic agents.
  • the compounds of this invention can be formulated neat or with a pharmaceutical carrier for administration, the proportion of which is determined by the solubility and chemical nature of the compound, chosen route of administration and standard pharmacological practice.
  • the pharmaceutical carrier may be solid or liquid.
  • a solid carrier can include one or more substances which may also act as flavoring agents, lubricants, solubilizers, suspending agents, fillers, glidants, compression aids, binders or tablet-disintegrating agents; it can also be an encapsulating material.
  • the carrier is a finely divided solid which is in admixture with the finely divided active ingredient.
  • the active ingredient is mixed with a carrier having the necessary compression properties in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably contain up to 99% of the active ingredient.
  • Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins.
  • Liquid carriers are used in preparing solutions, suspensions, emulsions, syrups, elixirs and pressurized compositions.
  • the active ingredient can be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fats.
  • the liquid carrier can contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators.
  • suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators.
  • suitable examples of liquid carriers for oral and parenteral administration include water (partially containing additives as above, e.g. cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols, e.g. glycols) and their derivatives, lethicins, and oils (e.g. fractionated coconut oil and arachis oil).
  • the carrier can also be an oily ester such as ethyl oleate and isopropyl myristate.
  • Sterile liquid carriers are useful in sterile liquid form compositions for parenteral administration.
  • the liquid carrier for pressurized compositions can be halogenated hydrocarbon or other pharmaceutically acceptable propellant.
  • Liquid pharmaceutical compositions which are sterile solutions or suspensions can be utilized by, for example, intramuscular, intraperitoneal or subcutaneous injection. Sterile solutions can also be administered intravenously.
  • the compounds of this invention can also be administered orally either in liquid or solid composition form.
  • the compounds of this invention may be administered rectally or vaginally in the form of a conventional suppository.
  • the compounds of this invention may be formulated into an aqueous or partially aqueous solution, which can then be utilized in the form of an aerosol.
  • the compounds of this invention may also be administered transdermally through the use of a transdermal patch containing the active compound and a carrier that is inert to the active compound, is non toxic to the skin, and allows delivery of the agent for systemic absorption into the blood stream via the skin.
  • the carrier may take any number of forms such as creams and ointments, pastes, gels, and occlusive devices.
  • the creams and ointments may be viscous liquid or semisolid emulsions of either the oil-in-water or water-in-oil type. Pastes comprised of absorptive powders dispersed in petroleum or hydrophilic petroleum containing the active ingredient may also be suitable.
  • occlusive devices may be used to release the active ingredient into the blood stream such as a semipermeable membrane covering a reservoir containing the active ingredient with or without a carrier, or a matrix containing the active ingredient.
  • Other occlusive devices are known in the literature.
  • the dosage requirements vary with the particular compositions employed, the route of administration, the severity of the symptoms presented and the particular subject being treated. Based on the results obtained in the standard pharmacological test procedures, projected daily dosages of active compound would be 0J to 10 mg/kg administered parenterally (intravenous preferred), with projected daily oral dosage being approximately ten-fold higher. Anticipated intravenous administration would last for approximately 5-30 days following acute vascular injury (i.e., balloon angioplasty or transplantation) and for a longer duration for the treatment of chronic disorders. Treatment will generally be initiated with small dosages less than the optimum dose of the compound.
  • the pharmaceutical composition is in unit dosage form, e.g. as tablets or capsules.
  • the composition is sub-divided in unit dose containing appropriate quantities of the active ingredient;
  • the unit dosage forms can be packaged compositions, for example, packaged powders, vials, ampoules, pre filled syringes or sachets containing liquids.
  • the unit dosage form can be, for example, a capsule or tablet itself, or it can be the appropriate number of any such compositions in package form.
  • step 1 5-(Hepta-O-acetyI- ⁇ -D-maltosyloxymethyI)-2-methyl-l-nitrobenzene
  • step 4 N- ⁇ 5-[(4',6'-O-Benzylidene- ⁇ -D-maltosyl-oxy)-methyl]-2-methyl-phenyl ⁇ - acetamide
  • N- ⁇ 5-[(4',6'-O-benzylidene- ⁇ -D-maltosyl- oxy)-methyl]-2-methyl-phenyl ⁇ -acetamide 0.11 g, 1.20 mmol
  • pyridine 2.4 mL
  • p-toluenesulfonyl chloride 0.275 g, 1.44 mmol
  • step 6 N-(5- ⁇ [4',6'-O-Benzylidene-6-deoxy-6-(4-nitro-lH-imidazoM-yI)- ⁇ -D-maltosyl- oxy]-methyI ⁇ -2-methyl-phenyl)-acetamide
  • 4-nitroimidazole 51.5 mg, 0.456 mmol
  • DMF 1.5 mL
  • K 2 CO 3 28.6 mg, 0J07 mmol
  • step 2 N-(5- ⁇ [2,3,2',3'-Tetra-O-acetyI-4',6'-O-benzylidene-6-O-(4-toluenesulfonyl)- ⁇ -D- maltosyl]-oxy-methyI ⁇ -2-chloro-phenyl)-acetamide
  • N-(5- ⁇ [4',6'-O-benzylidene-6-O-(4- toluenesulfonyl)- ⁇ -D-maltosyl]-oxy-methyl ⁇ -2-chloro-phenyl)-acetamide (0.782 g,
  • step 3 N-(5- ⁇ [2,3,2',3'-Tetra-O-acetyl-4',6'-O-benzylidene-6-deoxy-6-(4-nitro-lH- imidazol-l-yI)- ⁇ -D-maltosyl]-oxy-methyI ⁇ -2-chloro-phenyl)-acetamide
  • step 1 N- ⁇ 5-[(2,2',3,3'-Tetra-O-acetyl-6-deoxy-6-azido-4',6'-O-benzylidene- ⁇ -D- maltosyl)-oxy-methyI]-2-chloro-phenyI ⁇ -acetamide
  • step 2 N- ⁇ 5-[(6-Deoxy-6-azido-4',6'-O-benzylidene- ⁇ -D-maltosyl)-oxy-methyl]-2- chloro-phenyI ⁇ -acetamide

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pulmonology (AREA)
  • Pain & Pain Management (AREA)
  • Vascular Medicine (AREA)
  • Rheumatology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
EP99960572A 1998-11-24 1999-11-23 Benzylmaltoside als inhibitoren der proliferation von glatten muskelzellen Withdrawn EP1133512A2 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US19843498A 1998-11-24 1998-11-24
US198434 1998-11-24
PCT/US1999/027824 WO2000031100A2 (en) 1998-11-24 1999-11-23 Benzylmaltosides as inhibitors of smooth muscle cell proliferation

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EP1133512A2 true EP1133512A2 (de) 2001-09-19

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EP (1) EP1133512A2 (de)
JP (1) JP2002530424A (de)
CN (1) CN1333784A (de)
AU (1) AU1743900A (de)
BR (1) BR9915571A (de)
CA (1) CA2350753A1 (de)
WO (1) WO2000031100A2 (de)

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Publication number Priority date Publication date Assignee Title
BR9915632A (pt) * 1998-11-24 2001-08-07 American Home Prod Benzilmaltosìdeos acilados como inibidores da proliferação de células musculares lisas
CN105367614B (zh) * 2015-11-24 2019-02-22 中国人民解放军第二军医大学 含有葡萄糖类脂肪酸衍生物的制备方法及其在医药领域的应用

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Publication number Priority date Publication date Assignee Title
IL115745A (en) * 1994-11-07 2000-11-21 American Home Prod Acylated benzylglycosides and pharmaceutical compositions containing them
BR9915622A (pt) * 1998-11-24 2001-08-14 American Home Prod Acetal benzilmaltosìdeos como inibidores de proliferação de células de músculo liso

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Title
See references of WO0031100A2 *

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JP2002530424A (ja) 2002-09-17
AU1743900A (en) 2000-06-13
CA2350753A1 (en) 2000-06-02
BR9915571A (pt) 2001-08-14
WO2000031100A2 (en) 2000-06-02
CN1333784A (zh) 2002-01-30
WO2000031100A3 (en) 2000-11-23

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