AR041739A1 - Compuestos derivados -3,4-dihidro-1h-pirimido[4,5-d]pirimidin-2-ona y con actividad antiproliferativa. - Google Patents
Compuestos derivados -3,4-dihidro-1h-pirimido[4,5-d]pirimidin-2-ona y con actividad antiproliferativa.Info
- Publication number
- AR041739A1 AR041739A1 ARP030104000A ARP030104000A AR041739A1 AR 041739 A1 AR041739 A1 AR 041739A1 AR P030104000 A ARP030104000 A AR P030104000A AR P030104000 A ARP030104000 A AR P030104000A AR 041739 A1 AR041739 A1 AR 041739A1
- Authority
- AR
- Argentina
- Prior art keywords
- substituted
- lower alkyl
- conr13r14
- cor13
- so2nr13r14
- Prior art date
Links
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic 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
- C07D487/04—Ortho-condensed systems
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- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Se describen compuestos pirimido de la fórmula (1) que son inhibidores selectivos de la familia Src de tirosina cinasas. Estos compuestos y sus sales farmacéuticamente aceptables son agentes antiproliferativos útiles en el tratamiento o control de tumores sólidos, en particular, tumores de mama, colon, hígado y páncreas. Además se describen composiciones farmacéuticas que contienen estos compuestos, y el uso para el tratamiento de cáncer. Reivindicación 1: Un compuesto de fórmula (1) o una sal farmacéuticamente aceptable de éste en donde R1 se selecciona entre el grupo H, alquilo C1-10, alquilo C1-10 sustituido con hasta tres grupos seleccionados entre arilo, cicloalquilo, heteroarilo, heterociclo, -NR10R11, -OR12, -SR12, halógeno, -COR13, -CO2R13, -CONR13R14, -SO2NR13R14, -SOR13, -SO2R13, -CN, y -NO2, en donde los grupos arilo, cicloalquilo, heteroarilo y heterociclo pueden estar, cada uno, sustituidos en forma independiente con hasta tres grupos seleccionados entre NR10R11, -OR12, -SR12, halógeno, -COR13, -CO2R13,-CONR13R14, SO2NR13R14, SOR13, SO2R13, -CN, y -NO2, arilo, arilo sustituido con hasta tres grupos seleccionados entre alquilo inferior, NR10R11, -OR12, -SR12, halógeno, -COR13, -CO2R13, -CONR13R14, -SO2NR13R14, -SOR13, -SO2R13, -CN, y NO2; heteroarilo, heteroarilo sustituido con hasta tres grupos seleccionados entre alquilo inferior, NR10R11, -OR12, -SR12, halógeno, -COR13, -CO2R13, -CONR13R14, -SO2NR13R14, -SOR13, -SO2R13, -CN, y NO2; heterociclo, heterociclo sustituido con hasta tres grupos seleccionados entre alquilo inferior, -NR10R11, -OR12, -SR12, halógeno, -COR13, -CO2R13, -CONR13R14, -SO2NR13R14, -SOR13, -SO2R13, -CN, y -NO2; cicloalquilo C3-10, cicloalquilo C3-10 sustituido con hasta tres grupos seleccionados entre alquilo inferior, NR10R11, -OR12, -SR12, halógeno, -COR13, -CO2R13, -CONR13R14, -SO2NR13R14, -SOR13, -SO2R13, -CN, y NO2; alquenilo C2-10, alquenilo C2-10 sustituido con hasta tres grupos seleccionados entre NR10R11, -OR12, -SR12, halógeno, -COR13, -CO2R13, -CONR13R14, -SO2NR13R14, -SOR13, -SO2R13, -CN, y NO2, y alquinilo C2-10, sustituido con hasta tres grupos seleccionados entre NR10R11, -OR12, -SR12, halógeno, -COR13, -CO2R13, -CONR13R14, -SO2NR13R14, -SOR13, -SO2R13, -CN, y NO2; R2, R3 y R4 se seleccionan de manera independiente entre el grupo que consiste en H, NR10R11, -OR12, -SR12, alquilo C1-10, alquilo C1-10 sustituido con hasta tres grupos seleccionados entre cicloalquilo, heteroarilo, heterociclo, NR10R11, -OR12, -SR12, halógeno, COR13, -CO2R13, -CONR13R14, -SO2NR13R14, -SOR13, -SO2R13, -CN, y NO2, y en donde los grupos cicloalquilo, heteroarilo y heterociclo pueden estar, cada uno, sustituidos independientemente con hasta tres grupos seleccionados entre alquilo inferior, -NR10R11, -OR12, -SR12, halógeno, -COR13, -CO2R13, -CONR13R14, -SO2NR13R14, -SOR13, -SO2R13, -CN, y -NO2, heteroarilo, heteroarilo sustituido con hasta tres grupos seleccionados entre alquilo inferior, NR10R11, -OR12, -SR12, halógeno, -COR13, -CO2R13, -CONR13R14, -SO2NR13R14, -SOR13, -SO2R13, -CN, y NO2 heterociclo sustituido con hasta tres grupos seleccionados entre alquilo inferior, -NR10R11, -OR12, -SR12, halógeno, -COR13, -CO2R13, -CONR13R14, -SO2NR13R14, -SOR13, -SO2R13, -CN, y NO2; cicloalquilo C3-10, cicloalquilo C3-10 sustituido con hasta tres grupos seleccionados entre alquilo inferior, NR10R11, -OR12, -SR12, halógeno, -COR13, -CO2R13, -CONR13R14, -SO2NR13R14, -SOR13, -SO2R13, -CN, y NO2; alquenilo C2-10, alquenilo C2-10 sustituido con hasta tres grupos seleccionados entre NR10R11, -OR12, -SR12, halógeno, -COR13, -CO2R13, -CONR13R14, -SO2NR13R14, -SOR13, -SO2R13, -CN, y NO2, alquinilo C2-10 y alquinilo C2-10, sustituido con hasta tres grupos seleccionados entre NR10R11, -OR12, -SR12, halógeno, -COR13, -CO2R13, -CONR13R14, -SO2NR13R14, -SOR13, -SO2R13, -CN, y NO2; siempre que por lo menos uno de R2, R3 o R4 no sea H; R5, R6, R7 y R8 se seleccionan independientemente entre el grupo H, alquilo inferior, alquilo inferior sustituido con hidroxi o alcoxi, NR15R16, -OH, -OR17, -SR17, halógeno, -COR17, -CO2R17, -CONR17R18, -SO2NR17R18, -SOR17, -SO2R17, y -CN; R9 se selecciona entre el grupo H, como se muestra en el resto de fórmula (2) y COR17; R10 y R11 se seleccionan independientemente entre el grupo H; COR13, -CO2R13, -CONR13R14, -SO2R13, -SO2NR13R14, alquilo inferior, alquilo inferior sustituido con hidroxi, alcoxi o NR15R16, cicloalquilo, cicloalquilo sustituido con hidroxi, alcoxi, alquilo inferior, o NR15R16, heterociclo, y heterociclo sustituido con hidroxi, alcoxi, alquilo inferior, o NR15R16, o alternativamente, NR10R11 puede formar un anillo que tiene 3 a 7 átomos, en donde dicho anillo en forma opcional comprende uno o más heteroátomos adicionales, y está opcionalmente sustituido con el grupo que consiste en uno o más alquilo inferior, -OR12, COR13, -CO2R13, -CONR13R14, -SOR13, SO2R13, y -SO2NR13R14; R12 se selecciona entre el grupo H, alquilo inferior, COR13, -CONR13R14, alquilo C2-6 sustituido con hidroxi, alcoxi, o NR15R16, cicloalquilo, cicloalquilo sustituido con hidroxi, alcoxi, alquilo inferior, o NR15R16, heterociclo, y heterociclo sustituido con hidroxi, alcoxi, alquilo inferior, o NR15R16; R13 y R14 se seleccionan independientemente entre el grupo H, alquilo inferior, alquilo C2-6 sustituido con hidroxi, alcoxi, o NR15R16, cicloalquilo, cicloalquilo sustituido con hidroxi, alcoxi, alquilo inferior, o NR15R16, heterociclo, y heterociclo sustituido con hidroxi, alcoxi, alquilo inferior, o NR15R16, o, alternativamente, NR13R14 puede formar un anillo que tiene 3 a 7 átomos, en donde dicho anillo en forma opcional comprende uno o más heteroátomos adicionales, y está opcionalmente sustituido con el grupo que consiste en uno o más alquilo inferior, -OR17, -COR17, -CO2R17, -CONR17R18, -SO2R17, y -SO2NR17R18; R15 se selecciona entre el grupo H, alquilo inferior, COR17, y-CO2R17; y R16, R17 y R18 se seleccionan de manera independiente entre el grupo H, y alquilo inferior, o alternativamente, NR15R16 y NR17R18 puede formar, cada uno en forma independiente, un anillo que tiene 3 a 7 átomos, en donde dicho anillo en forma opcional comprende uno o más heteroátomos adicionales; R19 y R20 se seleccionan en forma independiente entre el grupo H, y alquilo inferior; y R21 se selecciona entre alquilo inferior, y alquilo C2-6 sustituido por hidroxi, alcoxi o NR15R16.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42367002P | 2002-11-04 | 2002-11-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR041739A1 true AR041739A1 (es) | 2005-05-26 |
Family
ID=32312700
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP030103999A AR041738A1 (es) | 2002-11-04 | 2003-10-31 | Compuestos derivados -3,4-dihidro-1h-pirimido[4,5-d]pirimidin-2-ona opticamente activos y su uso como agentes antitumorales. |
| ARP030104000A AR041739A1 (es) | 2002-11-04 | 2003-10-31 | Compuestos derivados -3,4-dihidro-1h-pirimido[4,5-d]pirimidin-2-ona y con actividad antiproliferativa. |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP030103999A AR041738A1 (es) | 2002-11-04 | 2003-10-31 | Compuestos derivados -3,4-dihidro-1h-pirimido[4,5-d]pirimidin-2-ona opticamente activos y su uso como agentes antitumorales. |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US7129351B2 (es) |
| EP (2) | EP1560832B1 (es) |
| JP (2) | JP2006513999A (es) |
| KR (4) | KR100774231B1 (es) |
| CN (2) | CN1711266A (es) |
| AR (2) | AR041738A1 (es) |
| AT (2) | ATE384725T1 (es) |
| AU (1) | AU2003276190A1 (es) |
| BR (2) | BR0316001A (es) |
| CA (2) | CA2502182A1 (es) |
| DE (2) | DE60319260T2 (es) |
| ES (2) | ES2298622T3 (es) |
| MX (2) | MXPA05004756A (es) |
| PL (2) | PL376924A1 (es) |
| RU (2) | RU2326882C2 (es) |
| WO (2) | WO2004041822A1 (es) |
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| CN1138778C (zh) | 1998-05-26 | 2004-02-18 | 沃尼尔·朗伯公司 | 用作细胞增殖抑制剂的二环嘧啶及二环3,4-二氢嘧啶化合物及用途 |
| AU769989B2 (en) | 1998-10-23 | 2004-02-12 | F. Hoffmann-La Roche Ag | Bicyclic nitrogen heterocycles |
| IL149100A0 (en) | 1999-10-21 | 2002-11-10 | Hoffmann La Roche | Heteroalkylamino-substituted bicyclic nitrogen heterocycles as inhibitors of p38 protein kinase |
| DE60032623T2 (de) | 1999-10-21 | 2007-10-11 | F. Hoffmann-La Roche Ag | Alkylamino-substituierte bicyclische heterocyclen als p38 protein-kinase-inhibitoren |
| MY141144A (en) | 2000-03-02 | 2010-03-15 | Smithkline Beecham Corp | 1, 5-disubstituted-3,4-dihydro-1h-pyrimido 4,5-dipyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases |
| AU9378401A (en) | 2000-08-31 | 2002-03-13 | Hoffmann La Roche | 7-oxo pyridopyrimidines as inhibitors of a cellular proliferation |
| GEP20063909B (en) | 2002-01-22 | 2006-08-25 | Warner Lambert Co | 2-(PYRIDIN-2-YLAMINO)-PYRIDO[2,3d] PYRIMIDIN-7-ONES |
| PA8577501A1 (es) * | 2002-07-25 | 2004-02-07 | Warner Lambert Co | Inhibidores de quinasas |
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2003
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- 2003-10-27 WO PCT/EP2003/011896 patent/WO2004041822A1/en active IP Right Grant
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- 2003-10-27 KR KR1020077016286A patent/KR100774230B1/ko not_active IP Right Cessation
- 2003-10-27 PL PL376916A patent/PL376916A1/pl not_active Application Discontinuation
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