AR050410A1 - MONOCICLIC HETEROCICLES AS KINASE INHIBITORS AND PHARMACEUTICAL COMPOSITION THAT CONTAINS - Google Patents

MONOCICLIC HETEROCICLES AS KINASE INHIBITORS AND PHARMACEUTICAL COMPOSITION THAT CONTAINS

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Publication number
AR050410A1
AR050410A1 ARP050101608A ARP050101608A AR050410A1 AR 050410 A1 AR050410 A1 AR 050410A1 AR P050101608 A ARP050101608 A AR P050101608A AR P050101608 A ARP050101608 A AR P050101608A AR 050410 A1 AR050410 A1 AR 050410A1
Authority
AR
Argentina
Prior art keywords
substituted
alkyl
aryl
cycloalkyl
heteroaryl
Prior art date
Application number
ARP050101608A
Other languages
Spanish (es)
Inventor
Robert Borzilleri
Lyndon A M Cornelius
Robert J Schmidt
Gretchen M Schroeder
Original Assignee
Bristol Myers Squibb Co
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 Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of AR050410A1 publication Critical patent/AR050410A1/en

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Abstract

Los compuestos que tienen la formula (1) o (2), y una composicion farmacéutica en la base al compuesto. Estos compuestos inhiben la actividad de la proteína tirosina-cinasa de los receptores del factor de crecimiento, siendo utiles como agentes anticancerosos. Reivindicacion 1: Un compuesto caracterizado porque tienen la formula (1) o (2), o un enantiomero, diastereoisomero, hidrato, solvato o sal farmacéuticamente aceptable de los mismos en donde: R1 es hidrogeno, alquilo, alquilo sustituido, cicloalquilo, cicloalquilo sustituido, arilalquilo, arilalquilo sustituido, arilo, arilo sustituido, alquenilo, alquenilo sustituido, alquinilo, alquinilo sustituido, heteroarilo, heteroarilo sustituido, heterociclo, heterociclo sustituido, heteroarilalquilo, heteroarilalquilo sustituido, heterocicloalquilo o heterocicloalquilo sustituido; cada R2 es independientemente hidrogeno, halogeno, ciano, NO2, OR5, NR6R7, alquilo, alquilo sustituido, cicloalquilo, cicloalquilo sustituido, arilo, arilo sustituido, heteroarilo, heteroarilo sustituido, heterociclo, heterociclo sustituido, arilalquilo, arilalquilo sustituido, heterocicloalquilo, o heterocicloalquilo sustituido; B es O, NR8, NR8CH2, S, SO, SO2 o CR9R10; V es NR11 o -(CR37R38)p- con la condicion de que cuando V sea nitrogeno, R1 sea un alquilo o cicloalquilo; W y X son cada uno independientemente carbono o nitrogeno; Y se selecciona de oxígeno, azufre y NR12; Z es -CR13R14-, o -(CR13R14)lNR15-; l es 0 a 2; n es 0 a 4 si W y X son ambos carbono, 0 a 3 si uno de X o W es nitrogeno, y 0 a 2 si X y W son ambos nitrogeno; p es 1 a 4; R3, R5, R6, R7, R8, R11 y R15 son independientemente seleccionados de hidrogeno, alquilo, alquilo sustituido, alquenilo, alquenilo sustituido, alquinilo, alquinilo sustituido, cicloalquilo, cicloalquilo sustituido, arilo, arilo sustituido, heteroarilo, heteroarilo sustituido, heterociclo, heterociclo sustituido; R4 se selecciona de arilo, arilo sustituido, heteroarilo, heteroarilo sustituido, heterocicloalquilo y heterocicloalquilo sustituido, con la condicion de que: a) si R4 es fenilo: i) R4 no está sustituido con hidroxilo y amido; y ii) R4 no está sustituido con -NRSO2R- en donde R es alquilo o arilo; b) si R4 es piridilo, R4 no está sustituido con hidroxilo y metoxi; y c) si R4 es pirimidinilo, éste no está sustituido con =O; R9 y R10 son independientemente seleccionados de hidrogeno, alquilo, alquilo sustituido, cicloalquilo, cicloalquilo sustituido, arilo, arilo sustituido, heteroarilo, heteroarilo sustituido, heterocicloalquilo, o heterocicloalquilo sustituido; R12 se selecciona de hidrogeno, alquilo, alquilo sustituido, alquenilo, alquenilo sustituido, alquinilo, alquinilo sustituido, CN, NO2 o SO2NH2; R13 y R14 son independientemente seleccionados de hidrogeno, halogeno, alquilo, alquilo sustituido, alquenilo, alquenilo sustituido, alquinilo, alquinilo sustituido, cicloalquilo, cicloalquilo sustituido, arilo, arilo sustituido, heteroarilo, heteroarilo sustituido, heterocicloalquilo, heterocicloalquilo o sustituido o tomados conjuntamente forman un anillo carbocíclico o heterocíclico de 3 a 8 átomos; A se selecciona del grupo de formulas (3), en donde: D es S u O; m es 0 a 6; R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26 y R27 son independientemente seleccionados de hidrogeno, halogeno, NR30R31, OR32, CO2R33, CONR34R35, SO2R36, alquilo, alquilo sustituido, cicloalquilo, cicloalquilo sustituido, alquenilo, alquenilo sustituido, alquinilo, alquinilo sustituido, -CN, arilo, arilo sustituido, heteroarilo, heteroarilo sustituido, heterocicloalquilo, o heterocicloalquilo sustituido; R28 y R29 son independientemente seleccionados de hidrogeno, alquilo, alquilo sustituido, cicloalquilo, cicloalquilo sustituido, arilo, arilo sustituido, o tomados conjuntamente forman un anillo carbocíclico o heterocíclico de 3 a 8 átomos; R30, R31, R32, R33, R34, R35 y R36 son independientemente seleccionados de hidrogeno, alquilo, alquilo sustituido, alquenilo, alquenilo sustituido, alquinilo, alquinilo sustituido, cicloalquilo, cicloalquilo sustituido, alcoxicarbonilo, arilo, arilo sustituido, heteroarilo, heteroarilo sustituido, heterociclo, heterociclo sustituido, heterocicloalquilo, o heterocicloalquilo sustituido; y R37 y R38 son cada uno independientemente hidrogeno, halogeno o alquilo.The compounds having the formula (1) or (2), and a pharmaceutical composition based on the compound. These compounds inhibit the activity of the tyrosine kinase protein of growth factor receptors, being useful as anticancer agents. Claim 1: A compound characterized in that they have the formula (1) or (2), or an enantiomer, diastereoisomer, hydrate, solvate or pharmaceutically acceptable salt thereof wherein: R1 is hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl , arylalkyl, substituted arylalkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, heteroarylalkyl, substituted heteroarylalkyl, heterocycloalkyl or substituted heterocycloalkyl; each R2 is independently hydrogen, halogen, cyano, NO2, OR5, NR6R7, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, arylalkyl, substituted arylalkyl, heterocycloalkyl, or heterocycloalkyl replaced; B is O, NR8, NR8CH2, S, SO, SO2 or CR9R10; V is NR11 or - (CR37R38) p- with the proviso that when V is nitrogen, R1 is an alkyl or cycloalkyl; W and X are each independently carbon or nitrogen; And it is selected from oxygen, sulfur and NR12; Z is -CR13R14-, or - (CR13R14) lNR15-; l is 0 to 2; n is 0 to 4 if W and X are both carbon, 0 to 3 if one of X or W is nitrogen, and 0 to 2 if X and W are both nitrogen; p is 1 to 4; R3, R5, R6, R7, R8, R11 and R15 are independently selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle , substituted heterocycle; R4 is selected from aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl and substituted heterocycloalkyl, with the proviso that: a) if R4 is phenyl: i) R4 is not substituted with hydroxyl and amido; and ii) R4 is not substituted with -NRSO2R- where R is alkyl or aryl; b) if R4 is pyridyl, R4 is not substituted with hydroxyl and methoxy; and c) if R4 is pyrimidinyl, this is not substituted with = O; R9 and R10 are independently selected from hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, or substituted heterocycloalkyl; R12 is selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, CN, NO2 or SO2NH2; R13 and R14 are independently selected from hydrogen, halogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, heterocycloalkyl or substituted or taken together form a carbocyclic or heterocyclic ring of 3 to 8 atoms; A is selected from the group of formulas (3), where: D is S or O; m is 0 to 6; R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26 and R27 are independently selected from hydrogen, halogen, NR30R31, OR32, CO2R33, CONR34R35, SO2R36, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl , alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, -CN, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, or substituted heterocycloalkyl; R28 and R29 are independently selected from hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, or taken together form a carbocyclic or heterocyclic ring of 3 to 8 atoms; R30, R31, R32, R33, R34, R35 and R36 are independently selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, alkoxycarbonyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl , heterocycle, substituted heterocycle, heterocycloalkyl, or substituted heterocycloalkyl; and R37 and R38 are each independently hydrogen, halogen or alkyl.

ARP050101608A 2004-04-23 2005-04-22 MONOCICLIC HETEROCICLES AS KINASE INHIBITORS AND PHARMACEUTICAL COMPOSITION THAT CONTAINS AR050410A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US56484204P 2004-04-23 2004-04-23
US63917804P 2004-12-23 2004-12-23

Publications (1)

Publication Number Publication Date
AR050410A1 true AR050410A1 (en) 2006-10-25

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ARP050101608A AR050410A1 (en) 2004-04-23 2005-04-22 MONOCICLIC HETEROCICLES AS KINASE INHIBITORS AND PHARMACEUTICAL COMPOSITION THAT CONTAINS

Country Status (5)

Country Link
AR (1) AR050410A1 (en)
MY (1) MY143200A (en)
PE (1) PE20060339A1 (en)
RU (1) RU2350603C2 (en)
TW (1) TWI324926B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2692725A4 (en) * 2011-03-29 2014-09-17 Eisai R&D Man Co Ltd Method for producing phenoxypyridine derivative
TWI598336B (en) * 2011-04-13 2017-09-11 雅酶股份有限公司 Substituted benzene compounds

Also Published As

Publication number Publication date
TWI324926B (en) 2010-05-21
RU2350603C2 (en) 2009-03-27
MY143200A (en) 2011-03-31
TW200602023A (en) 2006-01-16
RU2006141096A (en) 2009-01-20
PE20060339A1 (en) 2006-04-21

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