WO2001070678A2 - Substituierte biphenylderivate - Google Patents
Substituierte biphenylderivate Download PDFInfo
- Publication number
- WO2001070678A2 WO2001070678A2 PCT/EP2001/003375 EP0103375W WO0170678A2 WO 2001070678 A2 WO2001070678 A2 WO 2001070678A2 EP 0103375 W EP0103375 W EP 0103375W WO 0170678 A2 WO0170678 A2 WO 0170678A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- biphenyl
- methanesulfonyl
- carbamimidoyl
- phenoxy
- amide
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C317/34—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring
- C07C317/38—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring with the nitrogen atom of at least one amino group being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfones
- C07C317/40—Y being a hydrogen or a carbon atom
-
- 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
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Definitions
- the invention relates to compounds of the formula I.
- substituted phenyl or naphthyl optionally substituted by -A, -OR 5 , -N (R 5 ) 2 , -N0 2 , -CN, -Hai, -NR 5 COA, -NR 5 COAr ', -NR 5 S0 2 A , -NR 5 S0 2 Ar ', -COOR 5 , -CON (R 5 ) 2 ( -COR 7 , -COAr' or S (0) n A may be substituted;
- R 2 -S (0) n A, -CF 3 , -COOR 7 , -OA;
- R 3 , R 4 independently of one another, -H, -A, -OR 5 , -N (R 5 ) 2 , -N0 2 , -CN, -Hai, -NR 5 COA, -NR 5 COAr ⁇ -NR 5 S0 2 A, -NR 5 S0 2 Ar ', -COOR 5 ,
- R 7 , R 8 independently of one another -H or -A;
- W - [C (R 5 R 6 )] m CONR 5 [C (R 5 R 6 )], -, -OC (R 5 R 6 ) m CONR 5 [C (R 5 R 6 )], -;
- Ar unsubstituted or single, double or triple by -A, -Ar ', -Het, -OR 5 , -N (R 5 ) 2 , -N0 2 , -CN, -Hai, -NR 5 COA, - NR 5 COAr, -NR 5 S0 2 A, -NR 5 S0 2 Ar ', -COOR 5 , -CON (R 5 ) 2 , -CONR 5 Ar', -COR 7 , -COAr ',
- Ar ' unsubstituted or single, double or triple by -A, -OR 7 , -N (R 7 ) 2 , -N0 2 , -CN, -Hai, -NR 7 COA, -NR 7 S0 2 A, -COOR 7 ,
- Het a mono- or dinuclear saturated, unsaturated or aromatic heterocycle with 1 to 4 N, O and / or S atoms, bonded via N or C, which is unsubstituted or mono-, di- or triple -A, -OR 7 , -N (R 7 ) 2 , -N0 2 , -CN, -Hai, -NR 7 COA, -NR 7 S0 2 A, -COOR 7 , -CON (R 7 ) 2 , - COR 7 , -S0 2 NR 7 , -S (0) n A and / or carbonyl oxygen may be substituted;
- I O or l; m: 1, 2 or 3; n: 0, 1 or 2;
- the invention also relates to the optically active forms, the racemates, the diastereomers and the hydrates and solvates, for example alcoholates, of these compounds.
- the invention was based on the task of finding new compounds with valuable properties, in particular those which can be used for the production of medicaments.
- the compounds of the formula I and their salts have very valuable pharmacological properties with good tolerability.
- they show factor Xa inhibitory properties and can therefore be used to combat and prevent thromboembolic disorders such as thrombosis, myocardial infarction, arteriosclerosis, inflammation, apoplexy, angina pectoris, restenosis after angioplasty and intermittent claudication.
- the compounds of the formula I according to the invention can furthermore be inhibitors of the coagulation factors factor VIIa, factor IXa and thrombin of the blood coagulation cascade.
- the antithrombotic and anticoagulant effect of the compounds according to the invention is attributed to the inhibitory action against the activated coagulation protease, known under the name factor Xa, or to the inhibition of other activated serine proteases such as factor VIIa, factor IXa or thrombin.
- Factor Xa is one of the proteases involved in the complex process of blood clotting. Factor Xa catalyzes the conversion of prothrombin to thrombin. Thrombin cleaves fibrinogen into fibrin monomers which, after cross-linking, make an elementary contribution to thrombus formation. Activation of thrombin can lead to the occurrence of thromboembolic disorders. However, inhibition of thrombin can inhibit fibrin formation involved in thrombus formation.
- the inhibition of thrombin can be measured, for example, by the method of GF Cousins et al. in Circulation 1996, 94, 1705-1712. Inhibition of factor Xa can thus prevent thrombin from being formed.
- the compounds of formula I according to the invention and their salts interfere with the blood coagulation process by inhibiting factor Xa and thus inhibit the formation of thrombi.
- the inhibition of factor Xa by the compounds according to the invention and the measurement of the anticoagulant and antithrombotic activity can be determined by customary in vitro or in vivo methods.
- a suitable method is e.g. by J. Hauptmann et al. in Thrombosis and Haemostasis 1990, 63, 220-223.
- the measurement of the inhibition of factor Xa can e.g. using the method of T. Hara et al. in thromb. Haemostas. 1994, 71, 314-319.
- the coagulation factor VIa initiates the extrinsic part of the coagulation cascade after binding to the tissue factor and contributes to the activation of the factor X to factor Xa. Inhibition of factor VIIa thus prevents the formation of factor Xa and thus the subsequent formation of thrombin.
- the inhibition of the factor VIIa by the compounds according to the invention and the measurement of the anticoagulant and antithrombotic activity can be determined by customary in vitro or in vivo methods.
- a common method for measuring the inhibition of factor VIIa is e.g. by H. F. Ronning et al. in Thrombosis Research 1996, 84, 73-81.
- Coagulation factor IXa is generated in the intrinsic coagulation cascade and is also involved in the activation of factor X to factor Xa. Inhibition of factor IXa can therefore otherwise prevent factor Xa from being formed.
- the inhibition of factor IXa by the compounds according to the invention and the measurement of the anticoagulant and antithrombotic acti vity can be determined using conventional in vitro or in vivo methods.
- a suitable method is described, for example, by J. Chang et al. in Journal of Biological Chemistry 1998, 273, 12089-12094.
- the compounds of formula I can be used as active pharmaceutical ingredients in the
- thromboembolic disorders such as thrombosis, myocardial infarction, arteriosclerosis, inflammation, apoplexy, angina pectoris, restenosis after angioplasty and intermittent claudication.
- the invention further relates to the use of the compounds of the formula I and / or their physiologically acceptable salts for the production of pharmaceutical preparations, in particular by a non-chemical route. They can be brought into a suitable dosage form together with at least one solid, liquid and / or semi-liquid carrier or auxiliary and, if appropriate, in combination with one or more further active ingredients.
- the invention further relates to pharmaceutical preparations containing at least one compound of the formula I and / or one of its physiologically acceptable salts.
- These preparations can be used as medicinal products in human or veterinary medicine.
- Suitable carriers are organic or inorganic substances which are suitable for enteral (for example oral), parenteral or topical application and do not react with the new compounds, for example water, vegetable oils, benzyl alcohols, alkylene glycols, polyethylene glycols, glycerol triacetate , Gelatin, carbohydrates such as lactose or starch, magnesium stearate, talc, petroleum jelly.
- Tablets, pills, dragees, capsules, powders, granules, syrups, juices or drops are used for oral use, suppositories for rectal use, solutions, preferably oily or aqueous solutions, furthermore suspensions, emulsions or implants for parenteral use, for topical application of ointments, creams or powder.
- the new compounds can also be lyophilized and the lyophilizates obtained used, for example, for the production of injectables.
- the specified preparations can be sterilized and / or contain auxiliaries such as lubricants, preservatives, stabilizers and / or wetting agents, emulsifiers, salts for influencing the osmotic pressure, buffer substances, coloring, flavoring and / or several other active substances, eg one or more vitamins.
- auxiliaries such as lubricants, preservatives, stabilizers and / or wetting agents, emulsifiers, salts for influencing the osmotic pressure, buffer substances, coloring, flavoring and / or several other active substances, eg one or more vitamins.
- the compounds of the formula I and their physiologically acceptable salts can be used in the control and prevention of thromboembolic disorders such as thrombosis, myocardial infarction, arteriosclerosis, inflammation, apoplexy, angina pectoris, restenosis after angioplasty and intermittent claudication.
- thromboembolic disorders such as thrombosis, myocardial infarction, arteriosclerosis, inflammation, apoplexy, angina pectoris, restenosis after angioplasty and intermittent claudication.
- the substances according to the invention are generally preferably administered in doses between about 1 and 500 mg, in particular between 5 and 100 mg, per dosage unit.
- the daily dose is preferably between about 0.02 and 10 mg / kg body weight.
- the specific dose for each patient depends on a wide variety of factors, for example on the effectiveness of the particular compound used, on the age, body weight, general health, sex, on the diet, on the time and route of administration, on the rate of excretion and on the drug content - combination and severity of the respective disease to which the therapy applies. Oral application is preferred.
- the compounds of the formula I and also the starting materials for their preparation are prepared by methods known per se, as described in the literature (for example in the standard works such as Houben-Weyl, methods of organic chemistry, Georg-Thieme-Verlag, Stuttgart ) are described and under reaction conditions that are known and suitable for the reactions mentioned. Use can also be made of variants which are known per se and are not mentioned here.
- the starting materials can also be formed in situ, so that they are not isolated from the reaction mixture, but instead are immediately reacted further to give the compounds of the formula I.
- a synthesis is generally presented with which compounds of the formula I can be prepared.
- the synthesis can be varied by choosing suitable starting compounds.
- the synthesis is intended to show, by way of example only, one possible way of representing compounds of the formula I.
- other synthetic routes can also be used for the display.
- FIG. 1 An exemplary synthesis is shown in Fig. 1.
- the protected acid component A is reacted with the amine B to form a central amide bond to the compound C.
- the carbamimidoyl group is then reductively released to give the compound D according to the invention.
- the acid component A and the amine B can also be prepared by conventional synthetic methods.
- An exemplary synthesis is presented in Fig. 2 below.
- Fig. 2 Synthesis of an acid building block
- the phenol derivative E protected on the carbamimidoyl group is reacted with the protected bromocarboxylic acid F to give the compound G.
- the ester G is then saponified to give the carboxylic acid A ".
- the amines B can be represented, for example, in the following way (Fig. 3).
- Bromine-nitro-benzene H is converted to the biphenyl derivative J with the boronic acid derivative I.
- the methylthio group of biphenyl derivative I is then reacted with a suitable oxidizing agent such as sodium perborate to give methanesulfonyl compound K.
- the nitro group is reduced to the amine to obtain the amine component B ⁇ .
- the corresponding ethanesulfonyl compounds can also be prepared by an analogous synthetic route (Fig. 4).
- 2-Bromothiophenol is alkylated with iodoethane to the corresponding thioethane L. This is followed by conversion into boronic acid M and then, as in the synthesis from FIG. 3, the formation of a carbon bond to the biphenyl derivative N. The oxidation to the ethanesulfonyl compound takes place and then the reduction of the nitro group to the amine derivative B ".
- methylamine derivatives of the biphenyl part can be prepared from the corresponding nitrile compounds.
- An exemplary synthesis is shown in Fig. 7.
- Fig. 7 Synthesis of biphenyl-4-yl-methylamine derivatives
- synthesis routes shown can easily be varied by the person skilled in the art, for example by suitably changing the substitution pattern of the individual synthesis building blocks.
- Example 7 (1-Imino-1- ⁇ 3- [1- (2'-methanesulfonyl-biphenyl-4-ylcarbamoyl) butoxy] phenyl ⁇ methyl) carbamic acid methyl ester
- Example A Injection glasses A solution of 100 g of an active ingredient of the formula I and 5 g of disodium hydrogenphosphate is adjusted to pH 6.5 in 3 l of double-distilled water with 2N hydrochloric acid, sterile filtered, filled into injection glasses, lyophilized under sterile conditions and sterile closed. Each injection jar contains 5 mg of active ingredient.
- a mixture of 20 g of an active ingredient of the formula I is melted with 100 g of soy lecithin and 1400 g of cocoa butter, poured into molds and allowed to cool. Each suppository contains 20 mg of active ingredient.
- a solution is prepared from 1 g of an active ingredient of the formula I, 9.38 g of NaH 2 P0 4 2 H 2 0, 28.48 g of Na 2 HP0 4 12 H 2 0 and 0.1 g of benzalkonium chloride in 940 ml twice distilled water. It is adjusted to pH 6.8, made up to 1 I and sterilized by irradiation. This solution can be used in the form of eye drops.
- Example D ointment
- 500 mg of an active ingredient of the formula I are mixed with 99.5 g of petroleum jelly under aseptic conditions.
- Example F coated tablets
- Example E tablets are pressed, which are then coated in a conventional manner with a coating of sucrose, potato starch, talc, tragacanth and colorant.
- Example G capsules
- each capsule contains 20 mg of the active ingredient.
- a solution of 1 kg of active ingredient of the formula I in 60 l of double-distilled water is sterile filtered, filled into ampoules, lyophilized under sterile conditions and sealed sterile. Each ampoule contains 10 mg of active ingredient.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/239,397 US6946489B2 (en) | 2000-03-24 | 2001-03-23 | Substituted biphenyl derivatives |
CA002403500A CA2403500A1 (en) | 2000-03-24 | 2001-03-23 | Substituted biphenyl derivatives |
JP2001568890A JP2003528077A (ja) | 2000-03-24 | 2001-03-23 | 置換ビフェニル誘導体 |
EP01927797A EP1268413A2 (de) | 2000-03-24 | 2001-03-23 | Substituierte biphenylderivate |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10014645A DE10014645A1 (de) | 2000-03-24 | 2000-03-24 | Substituierte Biphenylderivate |
DE10014645.7 | 2000-03-24 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2001070678A2 true WO2001070678A2 (de) | 2001-09-27 |
WO2001070678A3 WO2001070678A3 (de) | 2002-04-04 |
Family
ID=7636185
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2001/003375 WO2001070678A2 (de) | 2000-03-24 | 2001-03-23 | Substituierte biphenylderivate |
Country Status (6)
Country | Link |
---|---|
US (1) | US6946489B2 (de) |
EP (1) | EP1268413A2 (de) |
JP (1) | JP2003528077A (de) |
CA (1) | CA2403500A1 (de) |
DE (1) | DE10014645A1 (de) |
WO (1) | WO2001070678A2 (de) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002037937A2 (en) * | 2000-11-07 | 2002-05-16 | Bristol-Myers Squibb Company | Acid derivatives useful as serine protease inhibitors |
WO2002042273A2 (en) * | 2000-11-07 | 2002-05-30 | Bristol-Myers Squibb Company | Acid derivatives useful as serine protease inhibitors |
WO2003064378A2 (de) * | 2002-01-31 | 2003-08-07 | Morphochem Aktiengesellschaft für kombinatorische Chemie | Verbindungen, die faktor xa-aktivität |
WO2003068217A1 (en) * | 2002-02-15 | 2003-08-21 | Endorecherche, Inc. | Biphenil derivatives and their use as antiandrogenic agents |
EP1487843A2 (de) * | 2002-03-20 | 2004-12-22 | Metabolex, Inc. | Substituierte phenylessigsäuren |
US6906192B2 (en) | 2000-11-07 | 2005-06-14 | Bristol Myers Squibb Company | Processes for the preparation of acid derivatives useful as serine protease inhibitors |
WO2006063697A1 (de) | 2004-12-16 | 2006-06-22 | Sanofi-Aventis Deutschland Gmbh | Hydroxybiphenyl-carbonsäuren und derivate, verfahren zu deren herstellung und deren verwendung |
US7365088B2 (en) | 2003-05-19 | 2008-04-29 | Sanofi-Aventis Deutschland Gmbh | Indazole-derivatives as factor Xa inhibitors |
US8362017B2 (en) | 2003-08-29 | 2013-01-29 | Exelixis, Inc. | C-kit modulators and methods of use |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4886948B2 (ja) * | 2001-09-28 | 2012-02-29 | キッセイ薬品工業株式会社 | ビフェニルエチルアミン誘導体およびその製造方法 |
MXPA06007203A (es) * | 2003-12-22 | 2006-08-18 | Merck & Co Inc | Alfahidroxiamidas como antagonistas o agonistas inversos de bradicinina. |
US7693868B2 (en) * | 2005-12-30 | 2010-04-06 | Sap Ag | Separation of employee data for different applications |
WO2007103996A1 (en) * | 2006-03-09 | 2007-09-13 | Bristol-Myers Squibb Company | 2-(aryloxy)acetamide factor viia inhibitors useful as anticoagulants |
DE102014203011A1 (de) * | 2014-02-19 | 2015-08-20 | Beiersdorf Ag | Kosmetische oder dermatologische Zubereitungen mit einem Gehalt an einem oder mehreren Biphenylamin-Derivaten und Verwendung von einem oder mehreren Biphenylamin-Derivaten zur Bräunung der Haut |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0540051A1 (de) * | 1991-10-31 | 1993-05-05 | Daiichi Pharmaceutical Co., Ltd. | Aromatische Amidinderivate und ihre Salze |
WO2000071512A1 (en) * | 1999-05-24 | 2000-11-30 | Cor Therapeutics, Inc. | INHIBITORS OF FACTOR Xa |
EP1078917A1 (de) * | 1998-02-17 | 2001-02-28 | Ono Pharmaceutical Co., Ltd. | Amidinoderivate und medikamente die diese als aktiven bestandteil enthalten |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1196379A2 (de) * | 1999-05-24 | 2002-04-17 | Cor Therapeutics, Inc. | Faktor xa-inhibitoren |
CA2374793A1 (en) * | 1999-05-24 | 2000-11-30 | Penglie Zhang | Inhibitors of factor xa |
-
2000
- 2000-03-24 DE DE10014645A patent/DE10014645A1/de not_active Withdrawn
-
2001
- 2001-03-23 EP EP01927797A patent/EP1268413A2/de not_active Withdrawn
- 2001-03-23 JP JP2001568890A patent/JP2003528077A/ja active Pending
- 2001-03-23 WO PCT/EP2001/003375 patent/WO2001070678A2/de not_active Application Discontinuation
- 2001-03-23 US US10/239,397 patent/US6946489B2/en not_active Expired - Fee Related
- 2001-03-23 CA CA002403500A patent/CA2403500A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0540051A1 (de) * | 1991-10-31 | 1993-05-05 | Daiichi Pharmaceutical Co., Ltd. | Aromatische Amidinderivate und ihre Salze |
EP1078917A1 (de) * | 1998-02-17 | 2001-02-28 | Ono Pharmaceutical Co., Ltd. | Amidinoderivate und medikamente die diese als aktiven bestandteil enthalten |
WO2000071512A1 (en) * | 1999-05-24 | 2000-11-30 | Cor Therapeutics, Inc. | INHIBITORS OF FACTOR Xa |
Cited By (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002042273A2 (en) * | 2000-11-07 | 2002-05-30 | Bristol-Myers Squibb Company | Acid derivatives useful as serine protease inhibitors |
WO2002042273A3 (en) * | 2000-11-07 | 2002-08-29 | Bristol Myers Squibb Co | Acid derivatives useful as serine protease inhibitors |
WO2002037937A3 (en) * | 2000-11-07 | 2002-08-29 | Bristol Myers Squibb Co | Acid derivatives useful as serine protease inhibitors |
US6642252B2 (en) | 2000-11-07 | 2003-11-04 | Bristol-Myers Squibb Company | Acid derivatives useful as serine protease inhibitors |
WO2002037937A2 (en) * | 2000-11-07 | 2002-05-16 | Bristol-Myers Squibb Company | Acid derivatives useful as serine protease inhibitors |
US6906192B2 (en) | 2000-11-07 | 2005-06-14 | Bristol Myers Squibb Company | Processes for the preparation of acid derivatives useful as serine protease inhibitors |
WO2003064378A2 (de) * | 2002-01-31 | 2003-08-07 | Morphochem Aktiengesellschaft für kombinatorische Chemie | Verbindungen, die faktor xa-aktivität |
WO2003064378A3 (de) * | 2002-01-31 | 2004-01-08 | Morphochem Ag Komb Chemie | Verbindungen, die faktor xa-aktivität |
US6933321B2 (en) | 2002-02-15 | 2005-08-23 | Endorecherche, Inc. | Antiandrogenic biphenyls |
WO2003068217A1 (en) * | 2002-02-15 | 2003-08-21 | Endorecherche, Inc. | Biphenil derivatives and their use as antiandrogenic agents |
EP1487843A2 (de) * | 2002-03-20 | 2004-12-22 | Metabolex, Inc. | Substituierte phenylessigsäuren |
JP2005520858A (ja) * | 2002-03-20 | 2005-07-14 | メタボレックス, インコーポレイテッド | 置換フェニル酢酸 |
EP1487843A4 (de) * | 2002-03-20 | 2010-03-10 | Metabolex Inc | Substituierte phenylessigsäuren |
US7365088B2 (en) | 2003-05-19 | 2008-04-29 | Sanofi-Aventis Deutschland Gmbh | Indazole-derivatives as factor Xa inhibitors |
US8362017B2 (en) | 2003-08-29 | 2013-01-29 | Exelixis, Inc. | C-kit modulators and methods of use |
WO2006063697A1 (de) | 2004-12-16 | 2006-06-22 | Sanofi-Aventis Deutschland Gmbh | Hydroxybiphenyl-carbonsäuren und derivate, verfahren zu deren herstellung und deren verwendung |
DE102004060542A1 (de) * | 2004-12-16 | 2006-07-06 | Sanofi-Aventis Deutschland Gmbh | Hydroxybiphenyl-Carbonsäuren und Derivate, Verfahren zu deren Herstellung und deren Verwendung |
Also Published As
Publication number | Publication date |
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JP2003528077A (ja) | 2003-09-24 |
EP1268413A2 (de) | 2003-01-02 |
CA2403500A1 (en) | 2002-09-18 |
US20040220241A1 (en) | 2004-11-04 |
WO2001070678A3 (de) | 2002-04-04 |
US6946489B2 (en) | 2005-09-20 |
DE10014645A1 (de) | 2001-09-27 |
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