DE102008031039A1 - Use of N-phenylquinazolin-4-amine derivatives as receptor tyrosine kinase inhibitor for accompanying treatment of organ transplantations - Google Patents
Use of N-phenylquinazolin-4-amine derivatives as receptor tyrosine kinase inhibitor for accompanying treatment of organ transplantations Download PDFInfo
- Publication number
- DE102008031039A1 DE102008031039A1 DE102008031039A DE102008031039A DE102008031039A1 DE 102008031039 A1 DE102008031039 A1 DE 102008031039A1 DE 102008031039 A DE102008031039 A DE 102008031039A DE 102008031039 A DE102008031039 A DE 102008031039A DE 102008031039 A1 DE102008031039 A1 DE 102008031039A1
- Authority
- DE
- Germany
- Prior art keywords
- phenylquinazolin
- amine derivatives
- kinase inhibitor
- tyrosine kinase
- receptor tyrosine
- 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- Withdrawn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 15
- MTSNDBYBIZSILH-UHFFFAOYSA-N n-phenylquinazolin-4-amine Chemical class N=1C=NC2=CC=CC=C2C=1NC1=CC=CC=C1 MTSNDBYBIZSILH-UHFFFAOYSA-N 0.000 title claims abstract description 7
- 238000002054 transplantation Methods 0.000 title abstract description 11
- 229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 title abstract 2
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims abstract description 13
- 229940120982 tarceva Drugs 0.000 claims abstract description 13
- 230000000694 effects Effects 0.000 abstract description 3
- 230000010534 mechanism of action Effects 0.000 abstract description 2
- 239000000824 cytostatic agent Substances 0.000 abstract 1
- 230000001085 cytostatic effect Effects 0.000 abstract 1
- 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 4
- 208000007204 Brain death 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
- 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
- 241000700605 Viruses Species 0.000 description 1
- 239000013543 active substance 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
- 208000035269 cancer or benign tumor 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
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 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
- 238000000034 method Methods 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
- 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
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- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Die vorliegende Erfindung betrifft ein neu Anwendung des Medikaments Tarceva 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 Tarceva for the concomitant treatment of organ transplants. This compound is characterized by a high effectiveness for prevention from organ rejections.
Organtransplantationen sind häufig mit Komplikationen verbunden, wie z. B. neurologische Komplikationen, Malignome, Virus oder Bakterien bedingte Infektionen, Entzuendungen, Durchblutungsstoerungen, die zu Amputationen der Extremitäten 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 and rejection reactions (hyperacute, acute or chronic) that can lead to the death of the patient.
Tarceva ist ein Kinaseinhibitor, der zur Behandlung spezieller Krebsarten eingesetzt wird. Der Wirkmechanismus und die Aktivität sind dabei mit der inhibitorischen Wirkung von Tarceva gegen die Rezeptortyrosinkinasen korreliert.Tarceva is a kinase inhibitor used to treat specific cancers is used. The mechanism of action and activity are there with the inhibitory effect of Tarceva against the Receptor tyrosine kinases correlated.
Aufgabe der vorliegenden Erfindung war die Erweiterung des Wirkbereiches von Kinaseinhibitor Tarceva im Bereich der Organtransplantation und damit die neuartige Anwendung von Tarceva zur begleitenden Behandlung von Organtransplantationen.task The present invention was the extension of the effective range of kinase inhibitor Tarceva in the field of organ transplantation and thus the novel use of Tarceva for concomitant treatment of organ transplants.
Es wurde gefunden, dass Wirkstoffe der allgemeinen Formel Tarceva 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 to contain active substances of the general formula Tarceva in Combination with common in transplantation medicine has much better dosage range and duration of use and the number of organ rejections lower the commonly used drugs and dosages.
Als
Tarcevaanaloga kommen für die erfindungsgemässe
Verwendung infrage: N-phenylquinazolin-4-aminderivate, wie sie in
der Patentschrift:
Schnur, Rodney C.; Arnold, Lee D. Preparation
of N-phenylquinazoline-4-amines as neoplasm inhibitors. PCT Int.
Appl. (1996), 63 pp.
String, Rodney C .; Arnold, Lee D. Preparation of N-phenylquinazolines-4-amines as neoplasm inhibitors. PCT Int. Appl. (1996), 63 pp.
Bevorzugtes
N-phenylquinazolin-4-aminderivat für die erfindungsgemässe
Verwendung ist Tarceva: N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine
(Tarceva) (II)
Die genannten Tarcevaderivate 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 Tarcevaderivate mentioned are used in quantities 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 Tarcevaanteil 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 N-phenylquinazolin-4-aminderivates.A typical dose for human use the Tarceva portion of this invention is dependent on the Method of administration, 10 mg to 100 mg (i.v.) or 0.1 mg to 1000 mg (p.o.), preferably 1 to 100 mg, more preferably 0.05 to 4 mg / kg body weight / minute at x i. v. or a biologically equivalent Amount of another N-phenylquinazolin-4-amine derivative.
Die vorliegende Erfindung betrifft somit die neuartige Anwendung von Tarceva zur begleitenden Behandlung von Organtransplantationen.The The present invention thus relates to the novel application of Tarceva 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:
-
A MODEL OF GRADUAL ONSET BRAIN DEATH FOR TRANSPLANT-ASSOCIATED 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 -
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
-
A MODEL OF GRADUAL ONSET BRAIN DEATH FOR TRANSPLANT-ASSOCIATED STUDIES IN RATS1. Transplantation. 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 -
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
Tarceva 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 Tarcevaunbehandelten Tieren.Tarceva or a biologically active derivative and other common transplant medicines were administered to the animals in various dose combinations before and after the transplantation of organ transplantation. The average survival time of the animals was statistically significantly longer compared to Tarcevaun treated animals.
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 9630347 A1 [0006] WO 9630347 A1 [0006]
Zitierte Nicht-PatentliteraturCited non-patent literature
- - A MODEL OF GRADUAL ONSET BRAIN DEATH FOR TRANSPLANT-ASSOCIATED 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 [0013] - A MODEL OF GRADUAL ONSET BRAIN DEATH FOR TRANSPLANT-ASSOCIATED STUDIES IN RATS1. Transplantation. 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 [0013]
- - 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 [0013] - 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 [0013]
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102008031039A DE102008031039A1 (en) | 2008-06-30 | 2008-06-30 | Use of N-phenylquinazolin-4-amine derivatives as receptor tyrosine kinase inhibitor for accompanying treatment of organ transplantations |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102008031039A DE102008031039A1 (en) | 2008-06-30 | 2008-06-30 | Use of N-phenylquinazolin-4-amine derivatives as receptor tyrosine kinase inhibitor for accompanying treatment of organ transplantations |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE102008031039A1 true DE102008031039A1 (en) | 2009-12-31 |
Family
ID=41360755
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE102008031039A Withdrawn DE102008031039A1 (en) | 2008-06-30 | 2008-06-30 | Use of N-phenylquinazolin-4-amine derivatives as receptor tyrosine kinase inhibitor for accompanying treatment of organ transplantations |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE102008031039A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010105110A1 (en) * | 2009-03-11 | 2010-09-16 | Ardea Biosciences, Inc. | Pharmaceutical combinations comprising rdea119/bay 869766 for the treatment of specific cancers |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996030347A1 (en) | 1995-03-30 | 1996-10-03 | Pfizer Inc. | Quinazoline derivatives |
-
2008
- 2008-06-30 DE DE102008031039A patent/DE102008031039A1/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996030347A1 (en) | 1995-03-30 | 1996-10-03 | Pfizer Inc. | Quinazoline derivatives |
Non-Patent Citations (2)
| Title |
|---|
| A MODEL OF GRADUAL ONSET BRAIN DEATH FOR TRANSPLANT-ASSOCIATED 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 |
| 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 |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010105110A1 (en) * | 2009-03-11 | 2010-09-16 | Ardea Biosciences, Inc. | Pharmaceutical combinations comprising rdea119/bay 869766 for the treatment of specific cancers |
| US8673876B2 (en) | 2009-03-11 | 2014-03-18 | Ardea Biosciences Inc. | Pharmaceutical combinations for treatment of specific cancers |
| US9220696B2 (en) | 2009-03-11 | 2015-12-29 | Ardea Biosciences, Inc. | Pharmaceutical combinations for treatment of specific cancers |
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| Date | Code | Title | Description |
|---|---|---|---|
| 8139 | Disposal/non-payment of the annual fee |