AR070224A1 - Inhibidores de proteina quinasa y uso de los mismos - Google Patents

Inhibidores de proteina quinasa y uso de los mismos

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Publication number
AR070224A1
AR070224A1 ARP090100188A ARP090100188A AR070224A1 AR 070224 A1 AR070224 A1 AR 070224A1 AR P090100188 A ARP090100188 A AR P090100188A AR P090100188 A ARP090100188 A AR P090100188A AR 070224 A1 AR070224 A1 AR 070224A1
Authority
AR
Argentina
Prior art keywords
alkyl
cycloalkyl
independently
nr5c
nr5r6
Prior art date
Application number
ARP090100188A
Other languages
English (en)
Original Assignee
Merck Serono Sa
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 Merck Serono Sa filed Critical Merck Serono Sa
Publication of AR070224A1 publication Critical patent/AR070224A1/es

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/73—Unsubstituted amino or imino radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/76—Nitrogen atoms to which a second hetero atom is attached
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Abstract

Una composicion farmacéutica que los comprende y el uso de los mismos para la preparacion de un medicamento para el tratamiento de enfermedades hiperproliferativas o inflamatorias. Reivindicacion 1: Un compuesto de la formula (1) en la que: W1 es CR8 o N, y W2 es -C-C:::C-Ar; o W1 es -C-C:::C-Ar, y W2 es CR8 o N; Y es -S-, -O-, -NH-, o -NHCH2-; X es N o N+ -O-; -------- representa un enlace sencillo o un doble enlace; Ar es arilo, carbociclilo, heteroarilo o heterociclilo; donde el arilo y heteroarilo están opcional e independientemente sustituidos con hasta 4 grupos representados por R3, y donde el carbociclilo y heterociclilo están opcional e independientemente sustituidos con hasta 4 grupos representados por R4; R1 y R2 se seleccionan independientemente entre H, halogeno, ciano, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alcoxi C1-6, cicloalquilo C3-8, heterocicloalquilo de 5-10 miembros, -C(O)OR5, -C(O)R5, -OC(O)R5, -C(O)NR5R6, -NR5C(O)NR5R6, -NR5C(O)OR5, -NR5C(O)R5, -NR5C(S)NR5R6, -S(O)pNR5R6, -NR5R6, -S(O)pR5, -NR5S(O)pR5, donde cada uno de dichos alquilo, alquenilo, alquinilo, alcoxi, cicloalquilo y heterocicloalquilo está sustituido o sin sustituir; o R1 y R2 pueden tomarse junto con los átomos intermedios para formar un anillo cicloalquilo C5-6 que está sustituido o sin sustituir; y p es un numero entero de 0 a 2; cada R3 es independientemente: i) halogeno, -X1-OH, -X1-CN, -X1-OR10, X1-CO2R10, -X1-NR10C(O)N(R10)2, -X1-NR10C(S)N(R10)2, -X1-NR10CO2R10, -X1-COR10, -X1-N(R10)2, -X1-N+(R10)3, -X1- OCOR10, -X1-SO2N(R10)2, -X1-S(O)nR10, -X1-NR10S(O)nR10, -X1-NR10COR10, -X1- OC(O)N(R10)2, -X1-CON(R10)2 o -X1-NR10CO2R10; o ii) alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, haloalquenilo C2-6, alquinilo C2-6 o haloalquinilo C2-6; o iii) arilo, aralquilo, ariloxi, heteroarilo, heteroaralquilo o heteroariloxi, cada uno opcional e independientemente sustituido con hasta 3 grupos seleccionados entre halogeno, -CN, -OH, -NH2, -NH-alquilo C1-6, -N-(alquilo C1-6)2, alquilo C1-6, haloalquilo C1-6, alcoxi C1-6, haloalcoxi C1-6, alcoxicarbonilo C1-6, -CONH2, -CONH-alquilo C1-6, -CON-(aIquilo C1-6)2, -CO-alquilo C1-6 o -CO2H;o iv) carbociclilo o heterociclilo, cada uno opcional e independientemente sustituido con hasta 3 grupos seleccionados entre halogeno, -CN, -OH, -NH2, -NH-alquilo C1-6, -N-(alquilo C1-6)2, alquil C1-6, haloalquilo C1-6, alcoxi C1-6, haloalcoxi C1-6, alcoxicarbonilo C1-6, -CONH2, -CONH-alquilo C1-6, -CON-(alquilo C1-6)2, -CO-alquilo C1-6, -CO2H, arilo, heteroarilo, oxo y tioxo; cada X1 es independientemente un enlace covalente, un alquileno C1-6, alquenileno C1-6 o alquinileno C1-6; cada R4 es independientemente un grupo representado por R3, oxo o tioxo; n es un numero entero de 0 a 2; cada R5 y R6 se seleccionan independientemente entre H, alquilo C1-4, cicloalquilo C3-8 o fenilo; donde dichos alquilo, cicloalquilo y fenilo están opcional e independientemente sustituidos con halogeno, -CN, -OH, -NH2, -OCF3, -OMe o alquilo C1-3; R7 y R8 son independientemente H, halogeno, ciano, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, -OR5, cicloalquilo C3-8, heterocicloalquilo de 5-10 miembros, -C(O)OR5, -C(O)R5, -OC(O)R5, -C(O)NR5R6, -NR5C(O)NR5R6, -NR5C(O)OR5, -NR5C(O)R5, -NR5C(S)NR5R6, -S(O)pNR5R6, -NR5R6, -SR5, -NR5S(O)pR5, donde cada uno de dichos alquilo, alquenilo, alquinilo, cicloalquilo y heterocicloalquilo está sustituido o sin sustituir; y cada R10 es independientemente H, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-8, heterocicloalquilo de 5-10 miembros, arilo, aralquilo, heteroarilo o heteroaralquilo; donde dichos alquilo, alquenilo, alquinilo, alcoxi, cicloalquilo, heterocicloalquilo, arilo, aralquilo, heteroarilo y heteroaralquilo están opcional e independientemente sustituidos con halogeno, -CN, -OH, -NH2, - NH-alquilo C1-3, -N-(alquilo C1-3)2, -CONH2, -CONH-alquilo C1-3, -CON-(alquilo C1-3)2, -CO-alquilo C1-3, -CO2H, alquilo C1-3, haloalquilo C1-3, alcoxi C1-3, haloalquilo C1-3, haloalcoxi C1-3, alquiloxicarbonilo C1-3, cicloalquilo C3-7 o fenilo; o una sal farmacéuticamente aceptable del mismo.
ARP090100188A 2008-01-22 2009-01-22 Inhibidores de proteina quinasa y uso de los mismos AR070224A1 (es)

Applications Claiming Priority (1)

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US1187208P 2008-01-22 2008-01-22

Publications (1)

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AR070224A1 true AR070224A1 (es) 2010-03-25

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Country Status (14)

Country Link
US (1) US20110282056A1 (es)
EP (1) EP2231282A1 (es)
JP (1) JP2011510004A (es)
KR (1) KR20100102651A (es)
CN (1) CN101918079A (es)
AR (1) AR070224A1 (es)
AU (1) AU2009206775A1 (es)
BR (1) BRPI0907236A2 (es)
CA (1) CA2709806A1 (es)
EA (1) EA020885B1 (es)
IL (1) IL206690A0 (es)
MX (1) MX2010007584A (es)
WO (1) WO2009094123A1 (es)
ZA (1) ZA201003420B (es)

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JP2012509342A (ja) 2008-11-20 2012-04-19 オーエスアイ・フアーマスーテイカルズ・インコーポレーテツド 置換ピロロ［２，３−ｂ］−ピリジンおよび−ピラジン
WO2011143646A1 (en) 2010-05-14 2011-11-17 OSI Pharmaceuticals, LLC Fused bicyclic kinase inhibitors
AR081039A1 (es) 2010-05-14 2012-05-30 Osi Pharmaceuticals Llc Inhibidores biciclicos fusionados de quinasa
US8835472B2 (en) * 2010-09-02 2014-09-16 Boehringer Ingelheim International Gmbh Compounds, pharmaceutical compositions and uses thereof
US8877754B2 (en) * 2010-09-06 2014-11-04 Boehringer Ingelheim International Gmbh Compounds, pharmaceutical compositions and uses thereof
DE102011111400A1 (de) * 2011-08-23 2013-02-28 Merck Patent Gmbh Bicyclische heteroaromatische Verbindungen
WO2014121883A1 (en) 2013-02-07 2014-08-14 Merck Patent Gmbh Substituted acetylene derivatives and their use as positive allosteric modulators of mglur4
WO2014194242A2 (en) * 2013-05-31 2014-12-04 Nimbus Iris, Inc. Flt3 inhibitors and uses thereof
WO2014194245A2 (en) * 2013-05-31 2014-12-04 Nimbus Iris, Inc. Cdk8 inhibitors and uses thereof
US10195188B2 (en) 2016-06-13 2019-02-05 Chemocentryx, Inc. Method of treating pancreatic cancer
EP3468548B1 (en) * 2016-06-13 2021-08-04 ChemoCentryx, Inc. Methods of treating pancreatic cancer
JP2019527725A (ja) * 2016-08-15 2019-10-03 パデュー リサーチ ファウンデイション ４位置換アミノイソキノリン誘導体
US10449186B2 (en) * 2017-06-21 2019-10-22 University Of Kentucky Research Foundation Phenylethynyl-substituted benzenes and heterocycles for the treatment of cancer
KR20190043437A (ko) 2017-10-18 2019-04-26 씨제이헬스케어 주식회사 단백질 키나제 억제제로서의 헤테로고리 화합물

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DE4218978A1 (de) * 1992-06-10 1993-12-16 Merck Patent Gmbh 2,3-Dihydro-furo(2,3-b)pyridine
US7338957B2 (en) * 2003-08-28 2008-03-04 Irm Llc Compounds and compositions as protein kinase inhibitors
TWI339206B (en) * 2003-09-04 2011-03-21 Vertex Pharma Compositions useful as inhibitors of protein kinases
US7776869B2 (en) * 2004-10-18 2010-08-17 Amgen Inc. Heteroaryl-substituted alkyne compounds and method of use
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Also Published As

Publication number Publication date
IL206690A0 (en) 2010-12-30
EA020885B1 (ru) 2015-02-27
BRPI0907236A2 (pt) 2017-06-06
MX2010007584A (es) 2010-08-03
KR20100102651A (ko) 2010-09-24
WO2009094123A1 (en) 2009-07-30
US20110282056A1 (en) 2011-11-17
ZA201003420B (en) 2011-08-31
CA2709806A1 (en) 2009-07-30
AU2009206775A1 (en) 2009-07-30
CN101918079A (zh) 2010-12-15
JP2011510004A (ja) 2011-03-31
EA201000848A1 (ru) 2010-12-30
EP2231282A1 (en) 2010-09-29

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