ES2573682T3 - Agentes de interrupción vascular activados por MMP - Google Patents
Agentes de interrupción vascular activados por MMP Download PDFInfo
- Publication number
- ES2573682T3 ES2573682T3 ES12160556.2T ES12160556T ES2573682T3 ES 2573682 T3 ES2573682 T3 ES 2573682T3 ES 12160556 T ES12160556 T ES 12160556T ES 2573682 T3 ES2573682 T3 ES 2573682T3
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- Prior art keywords
- mmp
- vascular
- resin
- agents activated
- peptide
- Prior art date
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
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- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Un compuesto, o sal farmacéuticamente aceptable del mismo, que comprende un agente de interrupción vascular (VDA) que es un agente anticancerígeno ligado a un péptido que comprende un sitio de división proteolítica de matriz de metaloproteinasa (MMP) que comprende la secuencia de aminoácidos -Arg-Ser-Cit-Gly-Hof-Tyr-Leu-.
Description
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δH (600 MHz, CDCl3), 10.08 (1 H, amplio s, NH), 8.99 (1 H, d J 10.7, C11-H), 7.71 (2 H, d, J 6.2, C23-H, C24-H),
7.55 (1 H, s, C8-H), 7.49 (2 H, dd, J 6.5 y 6.5, C20-H, C27-H), 7.41 (1 H, d, J 10.2, C10-H), 7.33 (2 H, dd, J 6.2 y 6.2, C22-H, C25-H), 7.26-7.21 (2 H, m, C21-H, C26-H), 6.91 (2 H, d, J 8.3, C14-H, C17-H), 6.56 (2 H, d, J 7.2, C15-H, C16-H), 6.45 (1 H, s, C4-H), 5.93 (1 H, amplio s, NH), 5.28 (1 H, s, NH), 4.95-4.90‘ (1 H, m, C12-H), 4.60 (1 H, ddd, J 11.7, 5.8 y 6.9, C7-H), 4.39 (1 H, dd, J 8.9 y 8.6, C18-CH2), 4.29-4.24 (1 H, m, C18-CH2), 4.12 (1 H, dd, J 6.9 y 6.9, C19-H), 3.90 (3 H, s, OCH3), 3.84 (3 H, s, OCH3), 3.54 (3 H, s, OCH3), 3.08 (2 H, d, J 5.2, C13-CH2), 2.44 (1 H, dd, J
13.4 y 6.2, C5-CH2), 2.33-2.26 (1 H, m, C5-CH2), 2.15-2.09 (1 H, m, C6-CH2), 1.82 (3 H, s, CH3), 1.75-1.69 (1 H, m, C6-CH2); ES m/z (%) 770 [M+] (100).
Preparación de 4:
Resina de cloruro de 2-Clorotritilo (Novabiochem, malla 100-200 m, sustitución 1.4 mmolg-1, 589 mg, 0.765 mmol,
1.00 eq) se suspende en una solución de 3 (589 mg, 0.765 mmol, 1.00 eq), dimetilaminopiridina (10 mg, 76.5 µmol,
0.01 eq), DiPEA (247 mg, 1.913 mmol, 333 µL, 2.50 eq) y piridina (241 mg, 3.061 mmol, 248 µL, 4.00 eq) en THF (10 mL) y se agita durante 6 horas a 50° C. La resina posteriormente se filtra y se lava profundamente con THF. La resina luego se finaliza al lavar la resina cuidadosamente con metanol (CH2Cl2:MeOH:DiPEA 17:2:1, 100 mL). La resina 4 se seca durante la noche sobre P2O5. Peso de resina seca: 593 mg (carga 56%).
Procedimiento general para síntesis de profármacos activados con endopeptidasa
5 fluo-bala-glu-pro-cit-gly-hof-tyr-leu-tyr-colch
Como un ejemplo, el conjugado de péptido 5 se sintetiza utilizando síntesis de péptido en fase sólida convencional, a partir de derivado de colchicina inmovilizado 4, utilizando una estrategia con base en Fmoc.
Se logran ácidos de síntesis de péptido de estrategia Nα-Fmoc manualmente utilizando resina derivada de 2clorotritilo 4. La resina se hincha profundamente en DMF, seguido por eliminación del grupo protector N-Fmoc mediante tratamiento con 20% v/v de piperidina en DMF (3 x 3 min). Todos los acoplamientos se realizan en DMF, empleando 2.5 veces de exceso molar de aminoácidos protegidos de Nα-Fmoc (con grupos de protección de cadena lateral apropiados), y activados utilizando HCTU/HOBt/DiPEA. Se realizan desprotecciones de Nα-Fmoc utilizando 20% de piperidina en DMF (3 x 3 min). El éxito de acoplamientos y desprotecciones se monitoriza utilizando la prueba de Kaiser con basr rn ninhidrina. Se repiten los acoplamientos no exitosos. Después de la desprotección de Nα-Fmoc final, la cadena de péptido se finaliza con isotiocianato de fluoresceína (2.50 eq, en la presencia de DiPEA,
1.50 eq). El éxito de esta reacción también se monitoriza por la prueba de Kaiser.
Un residuo de β-alanina adicional se incorpora en la secuencia para superar la incompatibilidad del enlace de tiourea y las condiciones ácidas de la división (la tiourea se puede reorganizar, y el carbono carbonilo del enlace amida anterior se puede someter a ataque nucleófilo por la función similar sulfhihidrilo así formada. Esto conduce a la división del enlace amida, con la formación concomitante de una tiazolinona cíclica. LA tiazolinona se puede someter a redisposición en presencia de ácido acuoso para formar una tiohidantoína).
Sobre la terminación de la secuencia, la resina se lava (DMF, CH2Cl2, CH2Cl2/MeOH) y se seca en vacío sobre KOH a peso constante. Los péptidos se dividen a partir de la resina mediante acidolisis leve utilizando TFA-H2O triisopropilsilano 95:2.5:2.5 durante 2 h a temperatura ambiente, con desprotección de cadena lateral simultánea. Luego de división, el TFA se elimina bajo presión reducida. El producto crudo se extrae en 95% ácido acético acuoso y se liofiliza. El péptido crudo se analiza posteriormente utilizando HPLC de fase inversa y se purifica utilizando HPLC preparativo (pureza >97%). Las fracciones puras se combinan y se liofilizan. Se confirma la identidad mediante espectrometría de masas.
Adhesión potencial de la colchicina progenitora a una secuencia de péptidos es a través del anillo B
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Claims (1)
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imagen1 imagen2
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0707034 | 2007-04-12 | ||
GBGB0707034.5A GB0707034D0 (en) | 2007-04-12 | 2007-04-12 | Compounds |
Publications (1)
Publication Number | Publication Date |
---|---|
ES2573682T3 true ES2573682T3 (es) | 2016-06-09 |
Family
ID=38116587
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES08718877.7T Active ES2573228T3 (es) | 2007-04-12 | 2008-03-27 | Agentes disruptores vasculares activados por MMP |
ES12160565.3T Active ES2683168T3 (es) | 2007-04-12 | 2008-03-27 | Secuencia de escisión específica de MMP-14 |
ES12160556.2T Active ES2573682T3 (es) | 2007-04-12 | 2008-03-27 | Agentes de interrupción vascular activados por MMP |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES08718877.7T Active ES2573228T3 (es) | 2007-04-12 | 2008-03-27 | Agentes disruptores vasculares activados por MMP |
ES12160565.3T Active ES2683168T3 (es) | 2007-04-12 | 2008-03-27 | Secuencia de escisión específica de MMP-14 |
Country Status (16)
Country | Link |
---|---|
US (4) | US8691751B2 (es) |
EP (4) | EP3348282A1 (es) |
JP (4) | JP5537413B2 (es) |
CY (1) | CY1120368T1 (es) |
DK (3) | DK2481429T3 (es) |
ES (3) | ES2573228T3 (es) |
GB (1) | GB0707034D0 (es) |
HK (2) | HK1174534A1 (es) |
HR (1) | HRP20181043T1 (es) |
HU (3) | HUE029080T2 (es) |
LT (1) | LT2481429T (es) |
PL (3) | PL2481429T3 (es) |
PT (1) | PT2481429T (es) |
SI (1) | SI2481429T1 (es) |
TR (1) | TR201807811T4 (es) |
WO (1) | WO2008125800A2 (es) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0707034D0 (en) | 2007-04-12 | 2007-05-23 | St Andrews The | Compounds |
GB0819287D0 (en) * | 2008-10-22 | 2008-11-26 | Univ Bradford | Compounds |
GB2516882A (en) * | 2013-08-02 | 2015-02-11 | Univ Bradford | Tumour-targeted theranostic |
US9169337B2 (en) | 2014-03-12 | 2015-10-27 | Chevron Phillips Chemical Company Lp | Polymers with improved ESCR for blow molding applications |
GB2545169B (en) * | 2015-12-01 | 2019-10-09 | Ellipses Pharma Ltd | Taxane Prodrug Comprising A Membrane Type Matrix Metalloproteinase Cleavage Site |
JP7360169B2 (ja) | 2017-07-07 | 2023-10-12 | カトリック ユニヴェルシテット ルーヴェン | 無血管性または乏血管性微小腫瘍の治療 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1263473A2 (en) * | 2000-03-15 | 2002-12-11 | Bristol-Myers Squibb Pharma Company | Peptidase-cleavable, targeted antineoplastic drugs and their therapeutic use |
GB0018240D0 (en) * | 2000-07-25 | 2000-09-13 | Pharmacia & Upjohn Spa | Polymeric conjugates of antitumor agents |
GB0105929D0 (en) * | 2001-03-09 | 2001-04-25 | Btg Int Ltd | Physiologically activated prodrugs |
ES2556641T3 (es) | 2002-07-31 | 2016-01-19 | Seattle Genetics, Inc. | Conjugados de fármacos y su uso para tratar cáncer, una enfermedad autoinmune o una enfermedad infecciosa |
US20050106100A1 (en) | 2003-09-03 | 2005-05-19 | Harris Thomas D. | Compounds containing matrix metalloproteinase substrates and methods of their use |
US8420603B2 (en) | 2004-05-14 | 2013-04-16 | Abraxis Bioscience, Llc | SPARC and methods of use thereof |
ES2565543T3 (es) | 2005-01-24 | 2016-04-05 | Board Of Regents, The University Of Texas System | Construcciones de fusión a Fc de unión a fosfatidilserina y su uso terapéutico |
US20090022782A1 (en) | 2005-02-25 | 2009-01-22 | National University Corp. Hokkaido University | Blood Retainable Device Exhibiting Selective Degradability in Tumor Tissue |
US7714016B2 (en) * | 2005-04-08 | 2010-05-11 | Medarex, Inc. | Cytotoxic compounds and conjugates with cleavable substrates |
GB0707034D0 (en) | 2007-04-12 | 2007-05-23 | St Andrews The | Compounds |
GB0819287D0 (en) | 2008-10-22 | 2008-11-26 | Univ Bradford | Compounds |
GB2516882A (en) | 2013-08-02 | 2015-02-11 | Univ Bradford | Tumour-targeted theranostic |
-
2007
- 2007-04-12 GB GBGB0707034.5A patent/GB0707034D0/en not_active Ceased
-
2008
- 2008-03-27 US US12/595,482 patent/US8691751B2/en active Active
- 2008-03-27 EP EP18156526.8A patent/EP3348282A1/en not_active Withdrawn
- 2008-03-27 PL PL12160565T patent/PL2481429T3/pl unknown
- 2008-03-27 DK DK12160565.3T patent/DK2481429T3/en active
- 2008-03-27 EP EP12160556.2A patent/EP2481428B1/en active Active
- 2008-03-27 EP EP08718877.7A patent/EP2134372B1/en active Active
- 2008-03-27 HU HUE12160556A patent/HUE029080T2/en unknown
- 2008-03-27 DK DK12160556.2T patent/DK2481428T3/en active
- 2008-03-27 PT PT121605653T patent/PT2481429T/pt unknown
- 2008-03-27 ES ES08718877.7T patent/ES2573228T3/es active Active
- 2008-03-27 EP EP12160565.3A patent/EP2481429B1/en active Active
- 2008-03-27 LT LTEP12160565.3T patent/LT2481429T/lt unknown
- 2008-03-27 ES ES12160565.3T patent/ES2683168T3/es active Active
- 2008-03-27 PL PL12160556.2T patent/PL2481428T3/pl unknown
- 2008-03-27 DK DK08718877.7T patent/DK2134372T3/en active
- 2008-03-27 TR TR2018/07811T patent/TR201807811T4/tr unknown
- 2008-03-27 ES ES12160556.2T patent/ES2573682T3/es active Active
- 2008-03-27 PL PL08718877.7T patent/PL2134372T3/pl unknown
- 2008-03-27 JP JP2010502559A patent/JP5537413B2/ja not_active Expired - Fee Related
- 2008-03-27 HU HUE08718877A patent/HUE027528T2/en unknown
- 2008-03-27 WO PCT/GB2008/001043 patent/WO2008125800A2/en active Application Filing
- 2008-03-27 HU HUE12160565A patent/HUE038633T2/hu unknown
- 2008-03-27 SI SI200831959T patent/SI2481429T1/en unknown
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2013
- 2013-01-31 HK HK13101399.0A patent/HK1174534A1/zh not_active IP Right Cessation
- 2013-12-17 US US14/109,333 patent/US9358303B2/en active Active
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2014
- 2014-04-25 JP JP2014090990A patent/JP5911908B2/ja not_active Expired - Fee Related
- 2014-04-25 JP JP2014090991A patent/JP5931952B2/ja not_active Expired - Fee Related
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2016
- 2016-04-27 JP JP2016088836A patent/JP6170590B2/ja not_active Expired - Fee Related
- 2016-05-06 US US15/148,368 patent/US9956296B2/en active Active
-
2018
- 2018-03-16 US US15/923,564 patent/US10556014B2/en not_active Expired - Fee Related
- 2018-06-27 CY CY20181100663T patent/CY1120368T1/el unknown
- 2018-07-05 HR HRP20181043TT patent/HRP20181043T1/hr unknown
-
2019
- 2019-01-16 HK HK19100772.3A patent/HK1258466A1/zh unknown
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