WO2000031095A2 - Benzylmaltotriosides inhibiteurs de la prolifération des cellules des muscles lisses - Google Patents
Benzylmaltotriosides inhibiteurs de la prolifération des cellules des muscles lisses Download PDFInfo
- Publication number
- WO2000031095A2 WO2000031095A2 PCT/US1999/027775 US9927775W WO0031095A2 WO 2000031095 A2 WO2000031095 A2 WO 2000031095A2 US 9927775 W US9927775 W US 9927775W WO 0031095 A2 WO0031095 A2 WO 0031095A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- carbon atoms
- hydrogen
- independently
- alkyl
- nitro
- Prior art date
Links
- 0 **C1C=CC=C(CO*)C1 Chemical compound **C1C=CC=C(CO*)C1 0.000 description 4
Classifications
-
- 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
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
- C07H15/08—Polyoxyalkylene derivatives
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
Definitions
- This invention relates to the use of substituted benzylmaltotriosides 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; Karnovs y, 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 p,articular) 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 (a) the carbohydrate moiety is maltotriose and (b) 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; Stability 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.
- Gotsberger (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 all of the prior art in that the compounds (a) are benzylmaltotriosides which bear no structural resemblance to heparin.
- sulfated cyclodextrins or to sulfated lactobionic acid dimers, (b) contain no more than three contiguous sugar residues (trisaccharide) and (c) are of a defined structure.
- This invention provides benzylmaltotriosides of formula I
- R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 .and R 10 are each, independently, hydrogen, acyl of 2- 7 carbon atoms, perfluoroacyl of 2-10 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, benzoyl, benzyl or -SO 3 M; M is hydrogen, lithium, sodium, potassium or ammonium;
- R n is hydrogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, halogen, nitrile, nitro, or alkoxy of 1-6 carbon atoms;
- R 12 is hydrogen, nitro, amino, acylamino of 2-7 carbon atoms, perfluoroacylamino of 2-7 carbon atoms, alkylamino of 1-6 carbon atoms, perfluoroalkylamino of 1- 6 carbon atoms, dialklylamino where each alkyl chain is independently 1-6 carbon atoms, perfluorodialklylamino where each alkyl chain is independently 1-6 carbon atoms alkylsulfonylamino of 1-6 carbon atoms, perfluoroalkylsulfonylamino of 1-6 carbon atoms, arylsulfonylamino of 6-10 carbon atoms or arylsulfonylamino substituted with halo of 6-10 carbon atoms; or a pharmaceutically acceptable salt thereof.
- Alkyl, alkoxy, alkylsulfonylamino, acylamino 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
- R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are each, independently, hydrogen, acyl of 2-
- M is lithium, sodium, potassium or ammonium
- R ⁇ is halogen
- R I2 is nitro, amino, or acylamino of 2-7 carbon atoms; or a pharmaceutically acceptable salt thereof.
- More preferred compounds of this invention are benzylmaltosides of formula I
- R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are each, independently, hydrogen, acetyl, or -SO 3 M;
- M is lithium, sodium, potassium or ammonium
- R ⁇ is chloro
- R 12 is hydrogen, nitro, amino, or acetylamino; 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.
- R 1 , R 2 , R 3 , R4, R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R" and R 12 are as defined above.
- maltotriosyl bromide 1 is coupled with a benzyl alcohol 2 in the presence of a catalyst such as a mercuric bromide, mercuric cyanide, silver triflate or silver perchlorate in an aprotic solvent such as acetonitrile, dichloromethane, ether, toluene or nitromethane at temperatures ranging from -40 °C to reflux to yield glycoside 3.
- a catalyst such as a mercuric bromide, mercuric cyanide, silver triflate or silver perchlorate
- an aprotic solvent such as acetonitrile, dichloromethane, ether, toluene or nitromethane at temperatures ranging from -40 °C to reflux to yield glycoside 3.
- 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 gives an anilino compound 4.
- 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 gives an anilino compound 4.
- Coupling of 4 with an acid chloride or a sulfonyl 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 gives 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. Sulfation of some or all of the free hydroxyl groups on the sugars with a reagent such as sulfur trioxide-trimethylamine complex or sulfur trioxide-pyridine complex in a polar aprotic solvent such as dimethylformamide or dimethylsulfoxide at temperatures ranging from 0°C to 100°C to give compound 7.
- a base such as sodium methoxide in methanol or aqueous sodium hydroxide in methanol at ambient temperature to reflux to yield 6.
- 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 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.
- a variety of 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.
- the pharmaceutical composition is in unit dosage form, e.g.
- 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-(Deca-O-acetyl- ⁇ -D-maltotriosyloxymet yI)-2-chIorophenylamine
- step 2 N-[5-(Deca-O-acetyl- ⁇ -D-maItotriosyloxymethyl)-2-chloro-phenyl]-acetami(le
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Pulmonology (AREA)
- Hospice & Palliative Care (AREA)
- Biochemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Neurology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU19198/00A AU1919800A (en) | 1998-11-24 | 1999-11-23 | Benzylmaltotriosides as inhibitors of smooth muscle cell proliferation |
EP99962844A EP1133506A2 (fr) | 1998-11-24 | 1999-11-23 | Benzylmaltotriosides inhibiteurs de la prolif ration des cellules des muscles lisses |
JP2000583923A JP2002530420A (ja) | 1998-11-24 | 1999-11-23 | 平滑筋細胞増殖の阻害薬としてのベンジルマルトトリオシド |
CA002350759A CA2350759A1 (fr) | 1998-11-24 | 1999-11-23 | Benzylmaltotriosides inhibiteurs de la proliferation des cellules des muscles lisses |
BR9915643-1A BR9915643A (pt) | 1998-11-24 | 1999-11-23 | Benzilmaltotriosìdeos como inibidores de proliferação de células do músculo liso |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US19880598A | 1998-11-24 | 1998-11-24 | |
US09/198,805 | 1998-11-24 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2000031095A2 true WO2000031095A2 (fr) | 2000-06-02 |
WO2000031095A3 WO2000031095A3 (fr) | 2001-01-04 |
Family
ID=22734935
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1999/027775 WO2000031095A2 (fr) | 1998-11-24 | 1999-11-23 | Benzylmaltotriosides inhibiteurs de la prolifération des cellules des muscles lisses |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP1133506A2 (fr) |
JP (1) | JP2002530420A (fr) |
CN (1) | CN1333778A (fr) |
AU (1) | AU1919800A (fr) |
BR (1) | BR9915643A (fr) |
CA (1) | CA2350759A1 (fr) |
WO (1) | WO2000031095A2 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7358366B2 (en) | 1999-04-23 | 2008-04-15 | Smithkline Beecham P.L.C. | Thiazolidinedione derivative and its use as antidiabetic |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996014325A1 (fr) * | 1994-11-07 | 1996-05-17 | American Home Products Corporation | Benzylglycosides acyles en tant qu'inhibiteurs de la proliferation cellulaire du muscle lisse |
-
1999
- 1999-11-23 BR BR9915643-1A patent/BR9915643A/pt not_active Application Discontinuation
- 1999-11-23 JP JP2000583923A patent/JP2002530420A/ja active Pending
- 1999-11-23 CN CN99815706A patent/CN1333778A/zh active Pending
- 1999-11-23 WO PCT/US1999/027775 patent/WO2000031095A2/fr not_active Application Discontinuation
- 1999-11-23 CA CA002350759A patent/CA2350759A1/fr not_active Abandoned
- 1999-11-23 AU AU19198/00A patent/AU1919800A/en not_active Abandoned
- 1999-11-23 EP EP99962844A patent/EP1133506A2/fr not_active Withdrawn
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996014325A1 (fr) * | 1994-11-07 | 1996-05-17 | American Home Products Corporation | Benzylglycosides acyles en tant qu'inhibiteurs de la proliferation cellulaire du muscle lisse |
Non-Patent Citations (4)
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7358366B2 (en) | 1999-04-23 | 2008-04-15 | Smithkline Beecham P.L.C. | Thiazolidinedione derivative and its use as antidiabetic |
Also Published As
Publication number | Publication date |
---|---|
CN1333778A (zh) | 2002-01-30 |
EP1133506A2 (fr) | 2001-09-19 |
JP2002530420A (ja) | 2002-09-17 |
BR9915643A (pt) | 2001-08-07 |
WO2000031095A3 (fr) | 2001-01-04 |
AU1919800A (en) | 2000-06-13 |
CA2350759A1 (fr) | 2000-06-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6451767B1 (en) | Benzylmaltotriosides as inhibitors of smooth muscle cell proliferation | |
US6291434B1 (en) | Benzylmaltotriosides as inhibitors of smooth muscle cell proliferation | |
EP1133506A2 (fr) | Benzylmaltotriosides inhibiteurs de la prolif ration des cellules des muscles lisses | |
US6187755B1 (en) | Benzylmaltosides as inhibitors of smooth muscle cell proliferation | |
US6362170B1 (en) | Benzylglycosylamides as inhibitors of smooth muscle cell proliferation | |
US7081448B2 (en) | Benzyllactobionamides as inhibitors of smooth muscle cell proliferation | |
US6339064B1 (en) | Benzylglycosylamides as inhibitors of smooth muscle cell proliferation | |
WO2000031100A2 (fr) | Benzylmaltosides utilises comme inhibiteurs de la proliferation cellulaire des muscles lisses | |
US6664243B1 (en) | Benzyllactobionamides as inhibitors of smooth muscle cell proliferation | |
US7132402B2 (en) | Acylated benzylmaltosides as inhibitors of smooth muscle cell proliferation | |
MXPA01005172A (en) | Benzylmaltotriosides as inhibitors of smooth muscle cell proliferation | |
US6258784B1 (en) | Acetal benzylmaltosides as inhibitors of smooth muscle cell proliferation | |
AU1743800A (en) | Acetal benzylmaltosides as inhibitors of smooth muscle cell proliferation | |
WO2000031093A2 (fr) | Benzylglycosylamides utilises comme inhibiteurs de proliferation des cellules du muscle lisse | |
JP2003521460A (ja) | 平滑筋細胞増殖の阻害薬としてのアセチル化ベンジルマルトシド | |
WO2000031092A2 (fr) | Benzyllactobionamides inhibiteurs de la proliferation des cellules des muscles lisses | |
EP1144426A2 (fr) | Benzylglycosylamides utilises comme inhibiteurs de la proliferation cellulaire des muscles lisses | |
MXPA01005178A (en) | Benzylmaltosides as inhibitors of smooth muscle cell proliferation | |
MXPA01005171A (es) | Bencilglicosilamidas como inhibidores de la proliferacion de celulas de musculoliso | |
MXPA01005175A (en) | Benzyllactobionamides as inhibitors of smooth muscle cell proliferation | |
MXPA01005173A (en) | Acylated benzylmaltosides as inhibitors of smooth muscle cell proliferation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 99815706.6 Country of ref document: CN |
|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
AK | Designated states |
Kind code of ref document: A3 Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A3 Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
ENP | Entry into the national phase in: |
Ref document number: 2350759 Country of ref document: CA Ref document number: 2350759 Country of ref document: CA Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1999962844 Country of ref document: EP |
|
ENP | Entry into the national phase in: |
Ref document number: 2000 583923 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 19198/00 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/2001/005172 Country of ref document: MX |
|
WWE | Wipo information: entry into national phase |
Ref document number: 512480 Country of ref document: NZ |
|
WWP | Wipo information: published in national office |
Ref document number: 1999962844 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1999962844 Country of ref document: EP |