AR073679A1 - CANCER PREVENTION AND TREATMENT WITH THE NON-EXPRESSION OF LKB1 SUPPRESSION OR MUTATION, PHARMACEUTICAL COMPOSITION. APPLICATIONS - Google Patents

CANCER PREVENTION AND TREATMENT WITH THE NON-EXPRESSION OF LKB1 SUPPRESSION OR MUTATION, PHARMACEUTICAL COMPOSITION. APPLICATIONS

Info

Publication number
AR073679A1
AR073679A1 ARP090103690A ARP090103690A AR073679A1 AR 073679 A1 AR073679 A1 AR 073679A1 AR P090103690 A ARP090103690 A AR P090103690A AR P090103690 A ARP090103690 A AR P090103690A AR 073679 A1 AR073679 A1 AR 073679A1
Authority
AR
Argentina
Prior art keywords
cancer
optionally substituted
mutation
suppression
expression
Prior art date
Application number
ARP090103690A
Other languages
Spanish (es)
Inventor
Yoshikazu Ohta
Sarah H Bacus
Scott A Shell
Original Assignee
Takeda Pharmaceutical
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Takeda Pharmaceutical filed Critical Takeda Pharmaceutical
Publication of AR073679A1 publication Critical patent/AR073679A1/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/12Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
    • C07D487/16Peri-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/14Ortho-condensed systems

Abstract

Método para prevenir o tratar cáncer mediante la no expresion de LKB1 (supresion o mutacion) al administrar un inhibidor de la tirosina quinasa EGFR/ErbB2, o la sal o el profármaco de los mismos a un mamífero. Una composicion farmacéutica que contiene al menos los inhibidores de la tirosina quinasa EGFR/ErbB2 para tratar o prevenir el cáncer con la no expresion de LKB1 (supresion o mutacion) el uso de los inhibidores de la tirosina quinasa EGFR/ErbB2 para preparar la composicion farmacéutica para tratar o prevenir el cáncer con la no expresion de LKB1 (supresion o mutacion). Reivindicacion 1: Un método para tratar o prevenir el cáncer con la no expresion de LK1 (supresion o mutacion) en un mamífero con necesidad de ello, caracterizado porque el método comprende administrar al mamífero una cantidad efectiva de al menos uno del compuesto (1), una sal del mismo o un profármaco del mismo, donde el compuesto (1) es representado por la formula (1) donde W es C(R1) o N, A es un grupo arilo opcionalmente sustituido o un grupo heteroarilo opcionalmente sustituido, X1 es -NR3-Y1-, -O-, -S-, -SO-, -SO2- o -CHR3-, donde R3 es un átomo de hidrogeno o un grupo hidrocarburo alifático sustituido en forma opcional o R3 está enlazada de manera opcional a un átomo de carbono o un heteroátomo en el grupo arilo o el grupo heteroarilo representado por A para formar una estructura cíclica sustituida de manera opcional y Y1 es un enlace simple o un alquileno C1-4 sustituido en forma opcional o un -O-(alquileno C1-4) sustituido en forma opcional, R1 es un átomo de hidrogeno o un grupo sustituido en forma opcional enlazado por medio de un átomo de carbono, un átomo de nitrogeno o un átomo de oxígeno y R2 es un átomo de hidrogeno o un grupo sustituido en forma opcional enlazado por medio de un átomo de carbono o un átomo de azufre o R1 y R2 o R2 y R3 están enlazados opcionalmente para formar una estructura cíclica sustituida de manera opcional, siempre que estén excluidos compuestos representados por las formulas (2). Reivindicacion 2: El método para tratar o prevenir el cáncer con la no expresion de LKB1 (supresion o mutacion) en un mamífero con necesidad de ello de acuerdo con le reivindicacion 1, caracterizado porque el cáncer con le no expresion de LKB1 (supresion o mutacion) en un mamífero con necesidad de ello es al menos uno seleccionado del grupo que consiste de cáncer de pulmon, cáncer de colon, cáncer de páncreas, melanoma, cáncer gastrointestinal, cáncer de rinon, cáncer rectal, cáncer del intestino delgado, cáncer de esofago, cáncer de prostata, cáncer de mama y cáncer de ovarios. Reivindicacion 4: El método para tratar o prevenir eh cáncer con la no expresion de LKB1 (supresion o mutacion) en un mamífero con necesidad de ello de acuerdo con la reivindicacion 1, caracterizado porque al menos uno del compuesto (1), una sal del mismo o un profármaco del mismo es al menos uno del compuesto (3), una sal del mismo o un profármaco del mismo donde el compuesto (3) es representado por la formula (3), donde R1a es un átomo de hidrogeno o un grupo sustituido en forma opcional enlazado por medio de un átomo de carbono, un átomo de nitrogeno o un átomo de oxígeno, R2a es un grupo opcionalmente sustituido enlazado por medio de un átomo de carbono o un átomo de azufre o R1a y R2a o R2a y R3a están enlazados opcionalmente para formar una estructura cíclica sustituida de manera opcional, R3a es un átomo de hidrogeno o un grupo hidrocarburo alifático sustituido en forma opcional o R3a está enlazado de manera opcional a un átomo de carbono del grupo fenilo adyacente para formar una estructura cíclica sustituida de manera opcional, Ba es un anillo benceno sustituido en forma opcional y Ca es un grupo arilo C6-18 sustituido de manera opcional o una sal del mismo. Reivindicacion 5: Un método para tratar o prevenir el cáncer con la no expresi6n de LKB1 (supresion o mutacion) en un mamífero con necesidad de ello, caracterizado porque el método comprende administrar al mamífero una cantidad efectiva de N-{2-[4-({3-cloro-4-[3-(trifluorometil) fenoxi]fenil)amino-5H-pirrolo [3, 2-d]-pirimidin-5-il]etil}-3-hidroxi-3-metilbutanamida, una sal de la misma o un profármaco de la misma. Reivindicacion 8: Una composicion farmacéutica para tratar o prevenir el cáncer con la no expresion de LKB1 (supresion o mutacion) en un mamífero con necesidad de ello caracterizado porque comprende N-{2-[4-({3-cloro-4-[3-(trifluorometil) fenoxi]fenil)amino-5H-pirrolo [3,2-d]-pirimidin-5-il]etil}-3-hidroxi-3-metilbutanamida, una sal de la misma o un profármaco de la misma en una cantidad terapéuticamente efectiva.Method to prevent or treat cancer by non-expression of LKB1 (suppression or mutation) by administering an EGFR / ErbB2 tyrosine kinase inhibitor, or the salt or prodrug thereof to a mammal. A pharmaceutical composition containing at least EGFR / ErbB2 tyrosine kinase inhibitors to treat or prevent cancer with non-expression of LKB1 (suppression or mutation) the use of EGFR / ErbB2 tyrosine kinase inhibitors to prepare the pharmaceutical composition to treat or prevent cancer with non-expression of LKB1 (suppression or mutation). Claim 1: A method for treating or preventing cancer with non-expression of LK1 (suppression or mutation) in a mammal in need thereof, characterized in that the method comprises administering to the mammal an effective amount of at least one of the compound (1) , a salt thereof or a prodrug thereof, wherein the compound (1) is represented by the formula (1) where W is C (R1) or N, A is an optionally substituted aryl group or an optionally substituted heteroaryl group, X1 is -NR3-Y1-, -O-, -S-, -SO-, -SO2- or -CHR3-, where R3 is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group or R3 is optionally linked to a carbon atom or a heteroatom in the aryl group or the heteroaryl group represented by A to form an optionally substituted cyclic structure and Y1 is a single bond or an optionally substituted C1-4 alkylene or a -O- ( C1-4 alkylene) optionally substituted, R1 is a hyd atom oxygen or an optionally substituted group linked by means of a carbon atom, a nitrogen atom or an oxygen atom and R2 is a hydrogen atom or an optionally substituted group linked by means of a carbon atom or a Sulfur atom or R1 and R2 or R2 and R3 are optionally linked to form an optionally substituted cyclic structure, provided that compounds represented by formulas (2) are excluded. Claim 2: The method of treating or preventing cancer with the non-expression of LKB1 (suppression or mutation) in a mammal in need thereof according to claim 1, characterized in that the cancer with non-expression of LKB1 (suppression or mutation) ) in a mammal in need of it is at least one selected from the group consisting of lung cancer, colon cancer, pancreatic cancer, melanoma, gastrointestinal cancer, kidney cancer, rectal cancer, small intestine cancer, esophageal cancer , prostate cancer, breast cancer and ovarian cancer. Claim 4: The method of treating or preventing cancer with the non-expression of LKB1 (suppression or mutation) in a mammal in need thereof according to claim 1, characterized in that at least one of the compound (1), a salt of the same or a prodrug thereof is at least one of the compound (3), a salt thereof or a prodrug thereof where the compound (3) is represented by the formula (3), where R1a is a hydrogen atom or a group optionally substituted by means of a carbon atom, a nitrogen atom or an oxygen atom, R2a is an optionally substituted group linked by means of a carbon atom or a sulfur atom or R1a and R2a or R2a and R3a are optionally linked to form an optionally substituted cyclic structure, R3a is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group or R3a is optionally linked to a carbon atom of the adjacent phenyl group In order to form an optionally substituted cyclic structure, Ba is an optionally substituted benzene ring and Ca is an optionally substituted C6-18 aryl group or a salt thereof. Claim 5: A method for treating or preventing cancer with non-expression of LKB1 (suppression or mutation) in a mammal in need thereof, characterized in that the method comprises administering to the mammal an effective amount of N- {2- [4- ({3-Chloro-4- [3- (trifluoromethyl) phenoxy] phenyl) amino-5H-pyrrolo [3,2-d] -pyrimidin-5-yl] ethyl} -3-hydroxy-3-methylbutanamide, a salt of the same or a prodrug thereof. Claim 8: A pharmaceutical composition for treating or preventing cancer with non-expression of LKB1 (suppression or mutation) in a mammal in need thereof characterized in that it comprises N- {2- [4 - ({3-chloro-4- [ 3- (trifluoromethyl) phenoxy] phenyl) amino-5H-pyrrolo [3,2-d] -pyrimidin-5-yl] ethyl} -3-hydroxy-3-methylbutanamide, a salt thereof or a prodrug thereof in a therapeutically effective amount.

ARP090103690A 2008-09-26 2009-09-25 CANCER PREVENTION AND TREATMENT WITH THE NON-EXPRESSION OF LKB1 SUPPRESSION OR MUTATION, PHARMACEUTICAL COMPOSITION. APPLICATIONS AR073679A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US10060308P 2008-09-26 2008-09-26

Publications (1)

Publication Number Publication Date
AR073679A1 true AR073679A1 (en) 2010-11-24

Family

ID=41382081

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP090103690A AR073679A1 (en) 2008-09-26 2009-09-25 CANCER PREVENTION AND TREATMENT WITH THE NON-EXPRESSION OF LKB1 SUPPRESSION OR MUTATION, PHARMACEUTICAL COMPOSITION. APPLICATIONS

Country Status (3)

Country Link
AR (1) AR073679A1 (en)
TW (1) TW201016703A (en)
WO (1) WO2010036928A1 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014159638A1 (en) * 2013-03-14 2014-10-02 Genentech, Inc. Predicting response to egfr inhibitors
US9944649B2 (en) * 2014-05-01 2018-04-17 Novartis Ag Compounds and compositions as toll-like receptor 7 agonists
TWI740873B (en) 2015-12-24 2021-10-01 日商協和麒麟股份有限公司 α, β unsaturated amide compounds

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HRP970371A2 (en) * 1996-07-13 1998-08-31 Kathryn Jane Smith Heterocyclic compounds
PE20011178A1 (en) * 2000-04-07 2001-11-19 Takeda Chemical Industries Ltd HETEROCYCLIC COMPOUNDS AND THEIR PRODUCTION
RU2389731C2 (en) * 2004-06-02 2010-05-20 Такеда Фармасьютикал Компани Лимитед Condensed heterocyclic compound

Also Published As

Publication number Publication date
WO2010036928A1 (en) 2010-04-01
TW201016703A (en) 2010-05-01

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