DE102008031040A1 - Use of 2-aminopyrimidine derivatives for the treatment of organ transplantation - Google Patents
Use of 2-aminopyrimidine derivatives for the treatment of organ transplantation Download PDFInfo
- Publication number
- DE102008031040A1 DE102008031040A1 DE102008031040A DE102008031040A DE102008031040A1 DE 102008031040 A1 DE102008031040 A1 DE 102008031040A1 DE 102008031040 A DE102008031040 A DE 102008031040A DE 102008031040 A DE102008031040 A DE 102008031040A DE 102008031040 A1 DE102008031040 A1 DE 102008031040A1
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- Germany
- Prior art keywords
- treatment
- organ transplantation
- aminopyrimidine derivatives
- iressa
- organ
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 210000000056 organ Anatomy 0.000 title claims abstract description 14
- 150000005006 2-aminopyrimidines Chemical class 0.000 title claims abstract description 6
- 238000002054 transplantation Methods 0.000 title abstract description 7
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 14
- 229940084651 iressa Drugs 0.000 claims description 10
- 239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 9
- 230000000694 effects Effects 0.000 abstract description 3
- 230000010534 mechanism of action Effects 0.000 abstract description 2
- 230000001506 immunosuppresive effect Effects 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- BUHVIAUBTBOHAG-FOYDDCNASA-N (2r,3r,4s,5r)-2-[6-[[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound COC1=CC(OC)=CC(C(CNC=2C=3N=CN(C=3N=CN=2)[C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)C=2C(=CC=CC=2)C)=C1 BUHVIAUBTBOHAG-FOYDDCNASA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000007204 Brain death Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Landscapes
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Die vorliegende Erfindung betrifft ein neu Anwendung des Medikaments Iressa zur begleitenden Behandlung von Organtransplantationen. Diese Verbindung zeichnet sich durch eine hohe Wirksamkeit zur Verhinderung von Organabstossungen aus.The The present invention relates to a new application of the medicament Iressa for the concomitant treatment of organ transplants. These Compound is characterized by a high effectiveness for prevention from organ rejections.
Organtransplantationen sind haeufig mit Komplikationen verbunden, wie z. B. neurologische Komplikationen, Malignome, Virus oder Bakterien bedingte Infektionen, Entzuendungen, Durchblutungsstoerungen, die zu Amputationen der Extremitaeten fuehren koennen und Abstossungsreaktionen (hyperakut, akut oder chronisch) die zum Tod des Patient fuehren koennen.organ transplants are often associated with complications such. B. neurological Complications, malignancies, virus or bacterial infections, Inflammations, circulatory disturbances leading to amputations of the Extremities can lead to and rejection reactions (hyperacute, acute or chronic) that can lead to the death of the patient.
Iressa ist ein Kinaseinhibitor, der zur Behandlung speziller Krebsarten eingesetzt wird. Der Wirkmechanismus and die Aktivitaet sind dabei mit der inhibitorischen Wirkung von Iressa gegen Rezeptortyrosinkinasen korreliert.Iressa is a kinase inhibitor used to treat specific cancers is used. The mechanism of action and the activity are included with the inhibitory effect of Iressa against receptor tyrosine kinases correlated.
Aufgabe der vorliegenden Erfindung war die Erweiterung des Wirkbereiches von Kinaseinhibitor Iressa im Bereich der Organtransplantation und damit die neuartige Anwendung von Iressa zur begleitenden Behandlung von Organtransplantationen.task The present invention was the extension of the effective range of kinase inhibitor Iressa in the field of organ transplantation and hence the novel application of Iressa for concomitant treatment of organ transplants.
Es wurde gefunden, dass Wirkstoffe der allgemeinen Formel (I) in Kombination mit in der Transplantationsmedizin ueblichen Medikamenten, eine wesentlich bessere Dosierungsbreite und Anwendungsdauer besitzt und die Zahl der Organabstossungen veringern gegenüber den herkoemmlich eingesetzten Medikamenten und Dosierungen.It has been found that active ingredients of the general formula (I) in combination with transgender medicine, one has much better dosage range and duration of use and the number of organ rejections lower the commonly used drugs and dosages.
Als
Iressaanaloga kommen für die erfindungsgemässe
Verwendung infrage: 2-Aminopyrimidinderivate, wie sie in der Patentschrift
Gibson, Keith Hopkinson. Preparation of haloanilinoquinazolines
as Class I receptor tyrosine kinase inhibitors. PCI Int. Appl. (1996),
50 pp.
Bevorzugtes
2-Aminopyrimidinderivat für die erfindungsgemässe
Verwendung ist Iressa:
N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine
(Iressa)(II)
N- (3-chloro-4-fluorophenyl) -7-methoxy-6- (3-morpholinopropoxy) quinazolin-4-amine (Iressa) (II)
Die genannten Iressaderivate werden in Mengen eingesetzt, die im Bereich der sonst für die Krebsbehandlung üblichen Menge liegen. Die entsprechend vorliegender Erfindung anzuwendende Menge hängt vom Umfang der durch die anderen Medikamente verursachten Nebenwirkungen ab.The Iressaderivate are used in amounts in the range the usual amount for cancer treatment lie. The amount applicable according to the present invention depends on the extent of the other medicines caused Side effects.
Die erfindungsgemässe Kombination wird vorzugsweise oral verabreicht, infundiert oder intramuskulär injiziert.The combination according to the invention is preferably administered orally, infused or injected intramuscularly.
Eine typische Dosis für die Anwendung am Menschen für den Iressaanteil dieser Erfindung ist, abhängig von der Applikationsart, 10 mg bis 100 mg (i. v.) oder 0,1 mg bis 1000 mg (p. o.), bevorzugt 1 bis 100 mg, besonders bevorzugt 0.05 bis 4 mg/kg Körpergewicht/Minute an x i. v. oder eine biologisch äquivalente Menge eines anderen 2-Aminopyrimidinderivates.A typical human dosage for the Isressa portion of this invention, depending on the mode of administration, is 10 mg to 100 mg (iv) or 0.1 mg to 1000 mg (po), preferably 1 to 100 mg, more preferably 0.05 to 4 mg / kg body weight / minute at x iv or a biologically equivalent amount another 2-aminopyrimidine derivative.
Die vorliegende Erfindung betrifft somit die neuartige Anwendung von Iressa zur begleitenden Behandlung von Organtransplantationen.The The present invention thus relates to the novel application of Iressa for the concomitant treatment of organ transplants.
Beispielexample
In verscheidenen Versuchen wurden Organe (Leber, Herz, Niere) zwischen Individuen einer Tierspezies (Maus, Ratte, Hamster, Kaninchen, Hund, Schwein) implantive ausgetauscht.In Various attempts were made between organs (liver, heart, kidney) Individuals of an animal species (mouse, rat, hamster, rabbit, dog, Pig) implanted exchanged.
Entsprechende Experimente sind in der Literatur beschrieben:Appropriate Experiments are described in the literature:
A MODEL OF GRADUAL ONSET BRAIN DEATH FOR TRANSPLANTASSOCIATED STUDIES IN RATS1.A MODEL OF GRADUAL ONSET BRAIN DEATH FOR TRANSPLANTASSOCIATED STUDIES IN RATS1.
-
Transplantation. 69(3): 427–430, February 15, 2000. Pratschke, J. 2 3; Wilhelm, M. J. 2; Kusaka, M. 2 4; Laskowski, I. 2; Tilney, N. L. 2 5 und Krupnick AS, Kreisel D, Engels FH, Szeto WY, Plappert T, Popma SH, Flake AW, Rosengard BR.Transplantation. 69 (3): 427-430, February 15, 2000. Pratschke, J. 2 3; Wilhelm, M.J. 2; Kusaka, M. 2 4; Laskowski, I. 2; Tilney, N.L. 2 5 and Krupnick AS, Kreisel D, Engels FH, Szeto WY, Plappert T, Popma SH, Flake AW, Rosengard BR.
A novel small animal model of left ventricular tissue engineering.
-
J Heart Lung Transplant. 2002 Feb; 21(2): 233–43
-
J heart lung transplant. 2002 Feb; 21 (2): 233-43
Iressa oder ein biologisch aktives Derivat und andere uebliche Transplantationsmedikamente wurden dabei vor und nach der Transplantation der Organtransplantation den Tieren in verschiedenen Dosiskombinationen verabreicht. Die durchschnittliche Uberlebensdauer der Tiere war statistisch signifikant laenger, im Vergleich zu Iressaunbehandelten Tieren.Iressa or a biologically active derivative and other common transplant medicines were doing before and after the transplantation of organ transplantation administered to the animals in different dose combinations. The average survival of the animals was statistically significant longer, compared to animals treated with Isandaun.
ZITATE ENTHALTEN IN DER BESCHREIBUNGQUOTES INCLUDE IN THE DESCRIPTION
Diese Liste der vom Anmelder aufgeführten Dokumente wurde automatisiert erzeugt und ist ausschließlich zur besseren Information des Lesers aufgenommen. Die Liste ist nicht Bestandteil der deutschen Patent- bzw. Gebrauchsmusteranmeldung. Das DPMA übernimmt keinerlei Haftung für etwaige Fehler oder Auslassungen.This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.
Zitierte PatentliteraturCited patent literature
- - WO 9633980 A1 [0006] WO 9633980 A1 [0006]
Zitierte Nicht-PatentliteraturCited non-patent literature
- - Transplantation. 69(3): 427–430, February 15, 2000. Pratschke, J. 2 3; Wilhelm, M. J. 2; Kusaka, M. 2 4; Laskowski, I. 2; Tilney, N. L. 2 5 und Krupnick AS, Kreisel D, Engels FH, Szeto WY, Plappert T, Popma SH, Flake AW, Rosengard BR. [0013] - Transplant. 69 (3): 427-430, February 15, 2000. Pratschke, J. 2 3; Wilhelm, MJ 2; Kusaka, M. 2 4; Laskowski, I. 2; Tilney, NL 2 5 and Krupnick AS, roundabout D, Engels FH, Szeto WY, Plankert T, Popma SH, Flake AW, Rosengard BR. [0013]
- - J Heart Lung Transplant. 2002 Feb; 21(2): 233–43 [0014] - J heart lung transplant. 2002 Feb; 21 (2): 233-43 [0014]
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102008031040A DE102008031040A1 (en) | 2008-06-30 | 2008-06-30 | Use of 2-aminopyrimidine derivatives for the treatment of organ transplantation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102008031040A DE102008031040A1 (en) | 2008-06-30 | 2008-06-30 | Use of 2-aminopyrimidine derivatives for the treatment of organ transplantation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE102008031040A1 true DE102008031040A1 (en) | 2009-12-31 |
Family
ID=41360756
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE102008031040A Withdrawn DE102008031040A1 (en) | 2008-06-30 | 2008-06-30 | Use of 2-aminopyrimidine derivatives for the treatment of organ transplantation |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE102008031040A1 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996033980A1 (en) | 1995-04-27 | 1996-10-31 | Zeneca Limited | Quinazoline derivatives |
-
2008
- 2008-06-30 DE DE102008031040A patent/DE102008031040A1/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996033980A1 (en) | 1995-04-27 | 1996-10-31 | Zeneca Limited | Quinazoline derivatives |
Non-Patent Citations (2)
| Title |
|---|
| J Heart Lung Transplant. 2002 Feb; 21(2): 233-43 |
| Transplantation. 69(3): 427-430, February 15, 2000. Pratschke, J. 2 3; Wilhelm, M. J. 2; Kusaka, M. 2 4; Laskowski, I. 2; Tilney, N. L. 2 5 und Krupnick AS, Kreisel D, Engels FH, Szeto WY, Plappert T, Popma SH, Flake AW, Rosengard BR. |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8139 | Disposal/non-payment of the annual fee |