ES2189455T3 - Nuevos agentes inhibidores de la urocinasa. - Google Patents
Nuevos agentes inhibidores de la urocinasa.Info
- Publication number
- ES2189455T3 ES2189455T3 ES99936570T ES99936570T ES2189455T3 ES 2189455 T3 ES2189455 T3 ES 2189455T3 ES 99936570 T ES99936570 T ES 99936570T ES 99936570 T ES99936570 T ES 99936570T ES 2189455 T3 ES2189455 T3 ES 2189455T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- radical
- optionally substituted
- formula
- group
- 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.)
- Expired - Lifetime
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0404—Lipids, e.g. triglycerides; Polycationic carriers
- A61K51/0406—Amines, polyamines, e.g. spermine, spermidine, amino acids, (bis)guanidines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0455—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0459—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Utilización de los compuestos de la Fórmula I**(Fórmula)** que se presentan en forma de racematos así como de compuestos con la configuración L ó D, y en los que R1 (a) es OH u OR4, siendo R4 un alquilo C1-C8 ramificado o no ramificado, cicloalquilo C3-C8 o aralquilo, eventualmente sustituido, (b) representa un grupo de la fórmula**(Fórmula)** en la que R5 y R6 son radicales arbitrarios, realizándose en particular que (i) R5 y R6 son H, (ii) R5 es H y R6 es un alquilo C1-C8 ramificado o no ramificado, aralquilo, o cicloalquilo C5-C8, eventualmente sustituido, (iii) R5 y R6 en cada caso independientemente, son un alquilo C1-C4 ramificado o no ramificado, eventualmente sustituido, o (iv) R5 es H y R6 es NH2 o un grupo amino sustituido en particular con arilo o heteroarilo, (v) R5 es H o un alquilo C1-C4 ramificado o no ramificado, eventualmente sustituido y R6 es el radical de un aminoácido, de un péptido o de un polipéptido, (c) representa un grupo de la fórmula **(Fórmula)** en la que m designa el número 1 ó 2, y en la cual uno o varios de los grupos metileno están sustituidos eventualmente, estando configurado el grupo (c) racémicamente o teniendo la configuración D ó L, y R7 tiene el significado de R1 en los apartados (a), (b) y (f), (d) representa un grupo de la fórmula **(Fórmula)** en la que p = r = 1, p = 1 y r = 2 ó p 7 = 2 y r = 1, y en la que uno o varios de los grupos metileno están eventualmente sustituidos, y Rtiene el significado de R1 en los apartados (a), (b) y (f), (e) representa un grupo piperidilo, que está eventualmente sustituido en una de las posiciones 2, 3 y 4, estando condensado eventualmente con los anillos heterocicloalifáticos de las fórmulas (c), (d), (e) otro anillo aromático o cicloalifático, en las posiciones 2, 3 ó 3, 4, referidas al heteroátomo, (f) representa un grupo de fórmula **(Fórmula)** en la que R8 (i) significa un radical alquilo C1-C6 o arilo eventualmente sustituido, (ii) significa un radical alcoxi C1-C6 ramificado o no ramificado,saturado o insaturado, o (iii) significa un radical fenoxi- o benciloxi-carbonilo eventualmente sustituido, (g) representa un radical acilo de fórmula -COX, realizándose que X (i) significa H, o un radical alquilo ramificado o no ramificado, eventualmente sustituido, (ii) significa un radical arilo o heteroarilo eventualmente sustituido, (iii) significa un radical cicloalquilo eventualmente sustituido, (h) representa un radical aralquilo, en el que el radical aromático está eventualmente sustituido, (i) representa un radical de amida de ácido carboxílico de fórmula-CONR''R'''', un radical de amida de ácido tiocarboxílico-CSNR''R'''' o un radical de amida de ácido acético -CH2-CONR''R'''', realizándose que (i) R¿ y R¿ son H, (ii) R¿ y R¿ son en cada caso independientemente, alquilo C1-C4, (iii) R¿ es H y R¿ es alquilo C1-C4, (iv) R¿ es H y R¿ es arilo, o (v) R¿ y R¿ forman con el átomo de nitrógeno un anillo heterocicloalifático con 5-7 miembros de anillo, que puede llevar un heteroátomo adicional,(j) representa un radical SO2-Y, en el que Y (i) significa un alquilo C1-C8 eventualmente sustituido, (ii) significa un arilo o heteroarilo, o respectivamente O-arilo o O-heteroarilo, eventualmente sustituido, (iii) es -NR¿R¿, realizándose que R¿ y R¿ significan en cada caso independientemente, H o alquilo C1-C3, (k) representa un anillo cicloalifático con 5 a 8 átomos de C, que está eventualmente sustituido, (l) representa un radical heteroarilo eventualmente sustituido, (m) representa un radical alquilo funcionalizado de la fórmula -(CH2)n-X, realizándose que la cadena de alquilo está ramificada o no ramificada, n significa = de 1 a 8 y el radical funcional X (i) representa un grupo hidroxilo, cuyo átomo de H está sustituido eventualmente con un grupo alquilo C1-C4, aralquilo, p.ej. bencilo o feniletilo, arilo, p.ej. fenilo, hidroxi-alquilo C1-C4 o con un grupo acilo CO-alquilo C1-C6, (ii) significa un átomo de halógeno, (iii) representa un grupo amino terciario de la fórmula -N(Alk)2, realizándose que los grupos alquilo poseen de 1 a 3 átomos de C y el átomo de nitrógeno pertenece eventualmente a un anillo heterocicloalifático con 5-7 miembros de anillo, que puede llevar un heteroátomo, S, adicional, R2 representa un radical fenilo eventualmente sustituido, R3 es H o alquilo C1-C4 ramificado o no ramificado y n significa 0 ó 1, o de sales de los compuestos, para la preparación de un agente destinado al diagnóstico, la terapia y la prevención de enfermedades asociadas con la urocinasa o con el receptor de urocinasa.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98113519 | 1998-07-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2189455T3 true ES2189455T3 (es) | 2003-07-01 |
Family
ID=8232314
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02016038T Expired - Lifetime ES2219607T3 (es) | 1998-07-20 | 1999-07-20 | Nuevo agente inhibidor de la urocinasa. |
| ES99936570T Expired - Lifetime ES2189455T3 (es) | 1998-07-20 | 1999-07-20 | Nuevos agentes inhibidores de la urocinasa. |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02016038T Expired - Lifetime ES2219607T3 (es) | 1998-07-20 | 1999-07-20 | Nuevo agente inhibidor de la urocinasa. |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US6624169B1 (es) |
| EP (2) | EP1098651B1 (es) |
| JP (1) | JP4603162B2 (es) |
| AT (2) | ATE230599T1 (es) |
| AU (1) | AU754958B2 (es) |
| BR (1) | BR9912327B1 (es) |
| CA (1) | CA2338073C (es) |
| DE (2) | DE59903981D1 (es) |
| ES (2) | ES2219607T3 (es) |
| MX (1) | MXPA01000553A (es) |
| PT (1) | PT1264828E (es) |
| WO (1) | WO2000004954A2 (es) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU9059798A (en) * | 1998-09-18 | 2000-04-10 | Pentapharm Ag | Urokinase inhibitors |
| DE10013715A1 (de) | 2000-03-20 | 2001-09-27 | Wilex Biotechnology Gmbh | Hochselektive Inhibitoren des Urokinase-Plasminogenaktivators |
| DE10029014A1 (de) * | 2000-06-15 | 2001-12-20 | Univ Schiller Jena | Urokinase-Hemmstoffe |
| WO2002074756A2 (de) | 2001-03-21 | 2002-09-26 | Pentapharm Ag | Urokinase-inhibitoren |
| US7838560B2 (en) * | 2002-03-11 | 2010-11-23 | The Medicines Company (Leipzig) Gmbh | Urokinase inhibitors, production and use thereof |
| DE10225876A1 (de) * | 2002-06-11 | 2003-12-24 | Wilex Ag | Guanidinophenylalaninverbindungen als Urokinase-Inhibitoren |
| DE10233632A1 (de) * | 2002-07-24 | 2004-02-05 | Wilex Ag | Formulierungen von Phenylalanin-Derivaten |
| AU2003253326A1 (en) * | 2002-07-25 | 2004-02-16 | Wilex Ag | Method for the production of phenylalanine derivatives |
| DE10238048A1 (de) * | 2002-07-25 | 2004-02-05 | Wilex Ag | Verfahren zur Herstellung von Phenylalanin-Derivaten |
| DE10301300B4 (de) | 2003-01-15 | 2009-07-16 | Curacyte Chemistry Gmbh | Verwendung von acylierten 4-Amidino- und 4-Guanidinobenzylaminen zur Inhibierung von Plasmakallikrein |
| DE10322191B4 (de) * | 2003-05-16 | 2014-02-27 | The Medicines Company (Leipzig) Gmbh | N-sulfonylierte Aminosäurederivate, Verfahren zu ihrer Herstellung und ihre Verwendung |
| DE10323898A1 (de) | 2003-05-26 | 2004-12-23 | Wilex Ag | Hydroxyamidin- und Hydroxyguanidin-Verbindungen als Urokinase-Hemmstoffe |
| DE10342108A1 (de) | 2003-09-11 | 2005-04-14 | Curacyte Chemistry Gmbh | Basisch-substituierte Benzylaminanaloga als Inhibitoren des Gerinnungsfaktors Xa, ihre Herstellung und Verwendung |
| EP1637529A1 (en) * | 2004-09-20 | 2006-03-22 | 4Sc Ag | Novel piperidin-4-yl-thiazole-carboxamide analogues as inhibitors of T-cell proliferation and uses thereof |
| DE102004045720A1 (de) * | 2004-09-21 | 2006-03-23 | Wilex Ag | Stabile Dosierungsform von Phenylalanin-Derivaten |
| EP2087885A1 (en) | 2005-06-24 | 2009-08-12 | Wilex AG | Use of urokinase inhibitors for the treatment and /or prevention of neuropathological diseases |
| DE102006050672A1 (de) | 2006-10-24 | 2008-04-30 | Curacyte Discovery Gmbh | Hemmstoffe des Plasmins und des Plasmakallikreins |
| CA2800684A1 (en) * | 2010-05-26 | 2011-12-01 | Expression Pathology, Inc. | Urokinase-type plasminogen activator protein/plasminogen activator inhibitor type-1 protein selected reaction monitoring assay |
| WO2012004678A2 (en) | 2010-07-07 | 2012-01-12 | The Medicines Company (Leipzig) Gmbh | Serine protease inhibitors |
| KR20210089265A (ko) | 2015-03-30 | 2021-07-15 | 서니브룩 리서치 인스티튜트 | 암 치료 방법 |
| KR101888249B1 (ko) * | 2015-09-24 | 2018-08-13 | 주식회사 엘지화학 | 화합물 및 이를 포함하는 유기 전자 소자 |
| AU2016336133B2 (en) * | 2015-10-06 | 2021-02-25 | Redhill Biopharma Ltd. | Combination therapies for treating cancer |
| IL295658A (en) | 2020-03-10 | 2022-10-01 | Redhill Biopharma Ltd | Treatment of coronavirus infection |
| US11471448B2 (en) | 2020-12-15 | 2022-10-18 | Redhill Biopharma Ltd. | Sphingosine kinase 2 inhibitor for treating coronavirus infection in moderately severe patients with pneumonia |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU541738B2 (en) | 1979-09-20 | 1985-01-17 | Nippon Chemiphar Co. Ltd. | Cyclohexane carboxylic acid derivatives |
| DE3577700D1 (de) * | 1984-11-30 | 1990-06-21 | Shosuke Okamoto | Lysinderivat und proteinase-inhibitor. |
| JPH05503300A (ja) * | 1990-11-15 | 1993-06-03 | ペンタファルム アクチェンゲゼルシャフト | メタ置換フェニルアラニン誘導体 |
| CZ245994A3 (en) * | 1993-02-10 | 1995-10-18 | Pentapharm Ag | Piperazides of substituted phenylalanine derivatives as thrombin inhibitors |
| US5550213A (en) * | 1993-12-27 | 1996-08-27 | Rutgers, The State University Of New Jersey | Inhibitors of urokinase plasminogen activator |
| AU3107795A (en) * | 1994-08-09 | 1996-03-07 | Pentapharm Ag | Inhibitors of the benzamidine type |
| DE9418185U1 (de) * | 1994-11-12 | 1995-02-23 | Richard Wolf Gmbh, 75438 Knittlingen | Behälter für medizinische Instrumente |
| CH689611A5 (de) * | 1995-03-01 | 1999-07-15 | Pentapharm Ag | Urokinase-Inhibitoren. |
| AU9059798A (en) | 1998-09-18 | 2000-04-10 | Pentapharm Ag | Urokinase inhibitors |
-
1999
- 1999-07-20 DE DE59903981T patent/DE59903981D1/de not_active Expired - Lifetime
- 1999-07-20 JP JP2000560945A patent/JP4603162B2/ja not_active Expired - Lifetime
- 1999-07-20 EP EP99936570A patent/EP1098651B1/de not_active Expired - Lifetime
- 1999-07-20 CA CA2338073A patent/CA2338073C/en not_active Expired - Fee Related
- 1999-07-20 BR BRPI9912327-4B1A patent/BR9912327B1/pt not_active IP Right Cessation
- 1999-07-20 DE DE59909210T patent/DE59909210D1/de not_active Expired - Lifetime
- 1999-07-20 WO PCT/EP1999/005145 patent/WO2000004954A2/de not_active Ceased
- 1999-07-20 AT AT99936570T patent/ATE230599T1/de active
- 1999-07-20 PT PT02016038T patent/PT1264828E/pt unknown
- 1999-07-20 MX MXPA01000553A patent/MXPA01000553A/es active IP Right Grant
- 1999-07-20 US US09/743,800 patent/US6624169B1/en not_active Expired - Lifetime
- 1999-07-20 AU AU51615/99A patent/AU754958B2/en not_active Ceased
- 1999-07-20 EP EP02016038A patent/EP1264828B1/de not_active Expired - Lifetime
- 1999-07-20 ES ES02016038T patent/ES2219607T3/es not_active Expired - Lifetime
- 1999-07-20 ES ES99936570T patent/ES2189455T3/es not_active Expired - Lifetime
- 1999-07-20 AT AT02016038T patent/ATE264103T1/de active
-
2002
- 2002-07-26 US US10/202,850 patent/US6680320B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ATE264103T1 (de) | 2004-04-15 |
| ATE230599T1 (de) | 2003-01-15 |
| BR9912327B1 (pt) | 2013-11-12 |
| DE59909210D1 (de) | 2004-05-19 |
| US6624169B1 (en) | 2003-09-23 |
| JP4603162B2 (ja) | 2010-12-22 |
| US20030013723A1 (en) | 2003-01-16 |
| WO2000004954A2 (de) | 2000-02-03 |
| EP1264828A1 (de) | 2002-12-11 |
| US6680320B2 (en) | 2004-01-20 |
| MXPA01000553A (es) | 2002-04-24 |
| WO2000004954A3 (de) | 2000-06-22 |
| CA2338073C (en) | 2010-09-21 |
| BR9912327A (pt) | 2001-05-02 |
| JP2002521348A (ja) | 2002-07-16 |
| EP1098651B1 (de) | 2003-01-08 |
| AU754958B2 (en) | 2002-11-28 |
| AU5161599A (en) | 2000-02-14 |
| PT1264828E (pt) | 2004-08-31 |
| EP1098651A2 (de) | 2001-05-16 |
| EP1264828B1 (de) | 2004-04-14 |
| DE59903981D1 (de) | 2003-02-13 |
| ES2219607T3 (es) | 2004-12-01 |
| CA2338073A1 (en) | 2000-02-03 |
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