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AR119209A1 - DERIVADOS DE PIRROLO[1,2-c]IMIDAZOL COMO INHIBIDORES DE EGFR - Google Patents

DERIVADOS DE PIRROLO[1,2-c]IMIDAZOL COMO INHIBIDORES DE EGFR

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Publication number
AR119209A1
AR119209A1 ARP200101748A ARP200101748A AR119209A1 AR 119209 A1 AR119209 A1 AR 119209A1 AR P200101748 A ARP200101748 A AR P200101748A AR P200101748 A ARP200101748 A AR P200101748A AR 119209 A1 AR119209 A1 AR 119209A1
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Argentina
Prior art keywords
fluoro
pyrrolo
thiazol
imidazol
acetamide
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ARP200101748A
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English (en)
Inventor
Cosimo Dolente
Annick Goergler
David Stephen Hewings
Georg Jaeschke
Bernd Kuhn
Yvonne Alice Nagel
Christa Ulrike Obst-Sander
Antonio Ricci
Daniel Rueher
Sandra Steiner
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Hoffmann La Roche
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Publication of AR119209A1 publication Critical patent/AR119209A1/es

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Abstract

Compuestos derivados de pirrolo[1,2-c]imidazol como inhibidores allostéricos de EGFR, composición farmacéutica que los comprende y su uso en el tratamiento del cáncer de pulmón no microcítico. Reivindicación 1: Un compuesto seleccionado entre 2,2,2-trifluoroacetato de 2-(4,7-dicloro-6-(4-(piperazin-1-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(4-etilpiperazin-1-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(2-morfolinopirimidin-5-il)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(1-ciclopropilpiperidin-4-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-[4,7-dicloro-6-(6-morfolin-4-ilpiridin-3-il)indazol-2-il]-2-[rac-(6R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il]-N-(1,3-tiazol-2-il)acetamida; clorhidrato de 2-[4,7-dicloro-6-(4-piperidin-4-ilfenil)indazol-2-il]-2-[rac-(6R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il]-N-(1,3-tiazol-2-il)acetamida; 2-[4,7-dicloro-6-[4-(1-etilpiperidin-4-il)fenil]indazol-2-il]-2-[rac-(6R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il]-N-(1,3-tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(rac-(3R,4R)-1-etil-3-fluoropiperidin-4-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(1-(2-fluoroetil)piperidin-4-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-[4,7-dicloro-6-[4-[2-(dimetilamino)etoxi]fenil]indazol-2-il]-2-[rac-(6R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il]-N-(1,3-tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(2-(dimetilamino)etil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(3-ciano-4-morfolinofenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((3R,4R)-1-etil-3-fluoropiperidin-4-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((3S,4S)-1-etil-3-fluoropiperidin-4-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-[4,7-dicloro-6-[4-[rac-(3S,4S)-1-etil-3-fluoro-4-piperidil]fenil]indazol-2-il]-2-[(6R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il]-N-tiazol-2-il-acetamida; 2-[4,7-dicloro-6-[4-[rac-(3R,4R)-1-etil-3-fluoro-4-piperidil]fenil]indazol-2-il]-2-[(6R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il]-N-tiazol-2-il-acetamida; rac-2-(4,7-dicloro-6-(4-(4-hidroxipiperidin-1-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(2-(dimetilamino)etoxi)-3-etilfenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-((2-(dimetilamino)etil)(metil)amino)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(2-(pirrolidin-1-il)etoxi)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((3aR,6aS)-2-etiloctahidrociclopenta[c]pirrol-5-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(1-(2-fluoropropil)piperidin-4-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(1-(2-metoxietil)piperidin-4-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(3-(4-(hidroximetil)piperidin-1-il)propil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-((dimetilamino)metil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-((dimetilamino)metil)-3-fluorofenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(3-((4-(hidroximetil)piperidin-1-il)metil)biciclo[1.1.1]pentan-1-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(2-(4-(hidroximetil)piperidin-1-il)etil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(2-(3-(hidroximetil)pirrolidin-1-il)etil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-((4-(hidroximetil)piperidin-1-il)metil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((3S,4S)-3-fluoro-1-(2-hidroxietil)piperidin-4-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((3R,4R)-3-fluoro-1-(2-hidroxietil)piperidin-4-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((3S,4S)-3-fluoro-1-(3-hidroxiciclobutil)piperidin-4-il)fenil)-2Hindazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((3R,4R)-3-fluoro-1-(3-hidroxiciclobutil)piperidin-4-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((3S,4S)-3-fluoro-1-(2-metoxietil)piperidin-4-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((3R,4R)-3-fluoro-1-(2-metoxietil)piperidin-4-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(3-(4-hidroxipiperidin-1-il)propil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-((4-hidroxipiperidin-1-il)metil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(3-((4-(hidroximetil)piperidin-1-il)metil)azetidin-1-il)fenil)-2Hindazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(2-(4-(1-hidroxietil)piperidin-1-il)etil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(4-(2-hidroxietil)piperazin-1-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-((6-hidroxi-2-azaespiro[3.3]heptan-2-il)metil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(6-(4-((2-oxa-6-azaespiro[3.3]heptan-6-il)metil)fenil)-4,7-dicloro-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(2-(4-hidroxipiperidin-1-il)etil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((4-fluoro-4-(hidroximetil)piperidin-1-il)metil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(4-(3-hidroxiciclobutil)piperazin-1-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(2-(hidroximetil)morfolino)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(2-(4-(hidroximetil)piperidin-1-il)etoxi)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(6-(4-(2,7-diazaespiro[3.5]nonan-2-il)fenil)-4,7-dicloro-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(2-(3-hidroxipirrolidin-1-il)etil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(4-(2-hidroxipropil)piperazin-1-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(6-(4-(1,4-diazabiciclo[3.2.1]octan-4-il)fenil)-4,7-dicloro-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(6-etil-2,6-diazaespiro[3.5]nonan-2-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(4-(3-hidroxipirrolidin-1-il)metil)piperidin-1-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(3-((4-(hidroximetil)piperidin-1-il)metil)ciclobutil)fenil)-2Hindazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(3-((4-hidroxipiperidin-1-il)metil)ciclobutil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(2-(4-hidroxipiperidin-1-il)etoxi)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((4-(2-hidroxietil)piperidin-1-il)metil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((2-(4-(hidroximetil)piperidin-1-il)etil)(metil)amino)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((2-(4-hidroxipiperidin-1-il)etil)(metil)amino)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((3aR,6aS)-5-etilhexahidropirrolo[3,4-c]pirrol-2(1H)-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(2-etil-2,6-diazaespiro[3.5]nonan-6-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(1-etilazetidin-3-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(1-(2-hidroxietil)azetidin-3-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((1-metilpiperidin-4-il)oxi)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-[4,7-dicloro-6-[4-[[1-(3-hidroxi-1-metil-propil)-4-piperidil]oxi]fenil]indazol-2-il]-2-[rac-(6R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il]-N-tiazol-2-il-acetamida; rac-2-(4,7-dicloro-6-(4-(1-(3-hidroxiciclobutil)piperidin-4-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(2-(6-hidroxi-2-azaespiro[3.3]heptan-2-il)etoxi)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((2-(3-(hidroximetil)azetidin-1-il)etil)(metil)amino)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((2-(3-hidroxiazetidin-1-il)etil)(metil)amino)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-((2-hidroxi-7-azaespiro[3.5]nonan-7-il)metil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(2-(2-hidroxi-7-azaespiro[3.5]nonan-7-il)etoxi)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-((7R,8aS)-7-hidroxihexahidropirrolo[1,2-a]pirazin-2(1H)-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(((4-hidroxiciclohexil)(metil)amino)metil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(((3-hidroxiciclohexil)(metil)amino)metil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-((4-metilpiperazin-1-il)metil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-((4-hidroxi-4-metilpiperidin-1-il)metil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-((3-metoxipirrolidin-1-il)metil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(((3aR,6aS)-tetrahidro-1H-furo[3,4-c]pirrol-5(3H)-il)metil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2- il)acetamida; rac-2-(4,7-dicloro-6-(4-(2-(3-(1-hidroxietil)azetidin-1-il)etil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(2-(2-metoxietil)amino)etil)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4,7-dicloro-6-(4-(4-etil-1,4-diazepan-1-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(1-(2-fluoroetil)piperidin-4-il)fenil)-2H-indazol-2-il)-2-(6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dicloro-6-(4-(1-etilpiperidin-4-il)fenil)-2H-indazol-2-il)-2-(6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4-cloro-7-metil-6-(4-morfolinofenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4-cloro-7-(difluorometil)-6-(4-morfolinofenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(4-cloro-6-(4-(1-etilpiperidin-4-il)fenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dimetil-6-(4-morfolinofenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(6-(4-((3S,4S)-1-etil-3-fluoropiperidin-4-il)fenil)-4,7-dimetil-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(6-(4-((3R,4R)-1-etil-3-fluoropiperidin-4-il)fenil)-4,7-dimetil-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(6-(4-(1-etilpiperidin-4-il)fenil)-4,7-dimetil-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(6-(4-(4-etilpiperazin-1-il)fenil)-4,7-dimetil-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(6-(4-(1-(dietilamino)metil)ciclopropil)fenil)-4,7-dimetil-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(6-(4-(2-(etil(metil)amino)etil)fenil)-4,7-dimetil-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4,7-dimetil-6-(6-morfolinopiridin-3-il)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(4-cloro-7-etil-6-(4-morfolinofenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(7-cloro-4-metil-6-(4-morfolinofenil)-2H-indazol-2-il)-2-(6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(7-cloro-6-(4-((3S,4S)-1-etil-3-fluoropiperidin-4-il)fenil)-4-metil-2H-indazol-2-il)-2-(6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(7-cloro-6-(4-((3R,4R)-1-etil-3-fluoropiperidin-4-il)fenil)-4-metil-2H-indazol-2-il)-2-(6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(7-cloro-4-metil-6-(4-morfolinofenil)-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-[7-cloro-4-metil-6-[4-[(3S,4S)-1-etil-3-fluoro-4-piperidil]fenil]indazol-2-il]-2-[(6R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il]-N-tiazol-2-il-acetamida; 2-[7-cloro-4-metil-6-[4-[(3R,4R)-1-etil-3-fluoro-4-piperidil]fenil]indazol-2-il]-2-[(6R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il]-N-tiazol-2-il-acetamida; 2-(7-cloro-6-(4-(1-(2-metoxietil)piperidin-4-il)fenil)-4-metil-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(7-cloro-6-(4-(1-(2-fluoropropil)piperidin-4-il)fenil)-4-metil-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; rac-2-(7-cloro-6-(4-(2-(4-(hidroximetil)piperidin-1-il)etoxi)fenil)-4-metil-2H-indazol-2-il)-2-((R)-6-fluoro-6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; 2-(7-bromo-4-cloro-6-(4-morfolinofenil)-2H-indazol-2-il)-2-(6,7-dihidro-5H-pirrolo[1,2-c]imidazol-1-il)-N-(tiazol-2-il)acetamida; o sales farmacéuticamente aceptables.
ARP200101748A 2019-06-21 2020-06-19 DERIVADOS DE PIRROLO[1,2-c]IMIDAZOL COMO INHIBIDORES DE EGFR AR119209A1 (es)

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