AR054416A1 - Pirrolo [2,3-b]piridin-4-il-aminas y pirrolo [2,3-b]pirimidin-4-il-aminas como inhibidores de las quinasas janus. composiciones farmaceuticas. - Google Patents
Pirrolo [2,3-b]piridin-4-il-aminas y pirrolo [2,3-b]pirimidin-4-il-aminas como inhibidores de las quinasas janus. composiciones farmaceuticas.Info
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- ora
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- 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
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- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
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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
Abstract
Reivindicacion 1:Un compuesto de la formula (1) o una prodroga o sal farmacéuticamente aceptable del mismo, donde: R1, R2 y R3 son cada uno, independientemente, H, halogeno, alquilo C1-4, alquenilo C2-4, alquinilo C2-4, haloalquilo C1-4, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rd, NRcC(O)Ora, S(O)Rb, S(O) NRcRd, S(O)2Rb o S(O)2NRcRd; R4 es H, alquilo C1-4, alquenilo C2-4, alquenilo C2-4, alquinilo C2-4, S(O)2R9, SOR9, cicloalquilo o heterocicloalquilo, donde dichos alquilo C1-4, alquenilo C2-4, alquinilo C2-4, cicloalquilo, heterocicloalquilo están, cada uno opcionalmente sustituidos con 1, 2 o 3 sustituyentes seleccionados a partir de halogeno, alquilo C1-4 alquenilo C2-4, alquinilo C2-4, haloalquilo C1-4, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, CN, NO2, Ora, SRa, C(O)Rb, C(O)NRcRd, C(O)Ora, OC(O)Rb. OC(O)NRcRd, NRcC(O)Rd, NRcC(O)Ora, S(O)Rb, S(O)NRcRd, S(O)2Rb y S(O)2NRcRd; R5 es cicloalquilo de 3 a 8 miembros, heterocicloalquilo de 3 a 8 miembros, -L-(cicloalquilo de 3 a 8 miembros), -L-(heterocicloalquilo de 3 a 8 miembros), cada uno sustituido con un R6y O, 1 o 2 R7; L es alquileno C1-4, alquenilenilo C4, alquinilenilo C2-4, O, S, NR14, CO, COO, OCO, NR14C(O)=, CONR14, SO, SO2, SONR14, SO2NR14 o NR14CONR14; R6 es -W1-W2-W3-W4-W5- W6-R13; W1 está ausente o es alquilenilo C1-4, alquenilenilo C2-4, alquinilenilo C2-4, arilo, heteroarilo, cicloalquilo o heterocicloalquilo, cada uno opcionalmente sustituido con 1, 2 o 3 sustituyentes seleccionados a partir de halogeno, CH, NO2, ON, =NH, =NOH, =NO-(alquilo C1-4), haloalquilo C1-4, alcoxi C1-4, haloalcoxi C1-4, amino, alquilamino C1-4 o dialquilamino C2-8; W2 está ausente o es alquilenilo C1-4, alquenilenilo C2-4, alquinilenilo C2-4, O, S, NR12, CO, COO, OCO, C(S), C(S)NR12, -C(=N-CH)-, NR12C(O)O, CONE12, SO, SO2SONR12, SO2NR12 o NR12CONR12, donde dichos alquilenilo C1-4, alquenilenilo C2-4, alquinilenilo C2-4, están cada uno opcionalmente sustituidos con 1, 2 o 3 sustituyentes seleccionados a partir de halogeno, OH, alcoxi C1-4, haloalcoxi C1-4, amino, alquilamino C1-4 o dialquilamino C2-8; W3 está ausente o es alquilenilo C1-4, alquenilenilo C2-4, alquinilenilo C2-4, arilo, cicloalquilo, heteroarilo o heterocicloalquilo, donde cada uno de dichos alquilenilo C1-4, alquenilenilo C2-4, alquinilenilo C2-4, arilo, cicloalquilo, heteroarilo o heterocicloalquilo está opcionalmente sustituido con 1, 2 o 3 sustituyentes seleccionados a partir de halogeno, CH, NO2, OH, =NH, =NOH, =NO-(alquilo C1-4), haloalquilo C1-4, alcoxi C1-4, haloalcoxi C1-4, amino, alquilamino C1-4 o dialquilamino C2-8; W4 está ausente o es alquinilenilo C1-4, alquenilenilo C2-4, alquinilenilo C2-4, O, S, NR12, CO, COO, OCO, -C(=N-CN)-, NR12C(O)O, CONR12, SO, SO2, SONR12, SO2NR12 o NR12CONR12, donde dichos alquinilenilo C1-4, alquinilenilo C2-4, alquenilenilo C2-4, alquinilenilo C2- 4 están, cada uno opcionalmente sustituido con 1, 2 o 3 sustituyentes seleccionados a partir de halogeno CN, NO2, OH, =NH, =NOH, =NO-(alquilo C1-4), haloalquilo C1-4 alcoxi C1-4, haloalcoxi C1-4, amino, alquilamino C1-4 o dialquilamino C2-8; W5 está ausente o es C1-4 alquilenilo, C2-4alquenilenilo, C2-4alquinilenilo, arilo, cicloalquilo, heteroarilo o heterocicloalquilo, donde dicho C1-4alquilenilo, C2-4 alquenilenilo, C2-4alquinilenilo, arilo, cicloalquilo, heteroarilo o heterocicloalquilo está opcionalmente sustituido con 1, 2 o 3 sustituyentes halogeno, CN, NO2, OH, =NH, =NOH, =NO-(C1-4 alquilo), C1-4haloalquilo, C1-4 alcoxi, C1-4, haloalcoxi, amino, C1-4 alquilamino o C2-8dialquilamino; W6 está ausente o es alquilo C1-4, alquenilo C2-4, alquinilo C2-4, O, S, NR12, CO, COO, OCO, -C(=N-CN)-, NR12C(O)O, CONR12, SO, SO2, SONR12, SO2NR12 o NR12CONR12, donde dichos alquilo C1-4, alquenilo C2-4, alquinilo C2-4 están, cada uno, opcionalmente sustituidos con 1, 2 o 3 sustituyentes seleccionados a partir de CN, NO2, OH, =NH, =NOH, =NO-(alquilo C1-4), haloalquilo C1-4, alcoxi C1-4, haloalcoxi C1-4, amino, alquilamino C1-4 o dialquilamino C2-8; Rx es halogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, haloalquilo C1-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, arilalquilo, cicloalquilalquilo, heteroarilalquilo, heterocicloalquilalquilo, CN, NO2, ORa'', SRa'', C(O)Rb'', C(O)NRc''Rd'', C(O)ORa'', OC(O)Rb'', OC(O)NRc''Rd'', NRc''Rd'', NRc''C(O)Rd'', NRc''C(O)ORa'', S(O)Rb'', S(O) NRc''Rd'', S(O)2Rb'', S(O)2NRc''Rd'', -(alquil C1-6)-CN, -(alquil C1-6)-NO2, -(alquil C1-6)-ORa'', -(alquil C1-6)-SRa'', -(alquil C1-6)-C(O)Rb'', -(alquil C1-6)-C(O)Rb'', -(alquil C1-6)-C(O)NRc''Rd'', - (alquil C1-6)-C(O)ORa'', -(alquil C1-6)-OC(O)Rb'', -(alquil C1-6)-OC(O)NRc''Rd'', -(alquil C1-6)-NRc''Rd'', (alquil C1-6)-NRc''C(O)Rd'', (alquil C1-6)-NRc''C(O)ORA'', -(alquil C1-6)-S(O)Rb'', -(alquil C1-6)-S(O)NRc''Rd'', -(alquil C1-6)- S(O)2Rb''o - (alquil C16)-S(O)2NRc''Rd''; R9 es alquilo C1-4, arilo, heteroarilo, cicloalquilo o heterocicloalquilo, cada uno opcionalmente sustituido con 1, 2 o 3 sustituyentes seleccionados a partir de halogeno, alquilo C1-4, alquenilo C2-4, alquinilo C2-4, haloalquilo C1-4, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, CN, NO2, ORa', C8O9NRc'Rd', C(O)ORa', OC(O)Rb', OC(O)NRc'Rd', NRc'Rd', NRc'C(O)Rd', NRc'C(O) ORa', S(O)Rb', S(O)NRcRd', S(O)2Rb' y S(O)2NRc'Rd'; R10 es halogeno, CN, NO2, OH, =NH, =NOH, =NO-(alquilo C1-4), haloalquilo C1-4, alcoxi C1-4, haloalcoxi C1-4amino, alquilamino C1-4 o dialquilamino C2-8 o alquilo C1-6 donde dicho alquilo C1-6 está opcionalmente sustituido con 1, 2 o 3 sustituyentes seleccionados a partir de halogeno, CN NO2, OH, amino, (alquil C1-4)amino, (dialquil C2-8)amino, haloalquilo C1-6, acilo C1-6, aciloxi C1-6, acilamino C1-6 -(alquil C1-6)-CN y -(alquil C1-6)-NO2; R12 y R14 son cada uno independientemente H o alquilo C1-6opcionalmente sustituido con 1, 2 o 3 sustituyentes seleccionados a partir de OH, CN NO2, amino, (alquil C1-4)amino, (dialquil C2-8)amino, haloalquilo C1-6, aciloxi C1-6, acilamino C1-6, -(alquil C1-6)-CN y -(alquil C1-6)-NO2; R13 es halogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, haloalquilo C1-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, arilalquilo, cicloalquilalquilo, heteroarilalquilo, heterocicloalquilalquilo, CN, NO2, ORa'', SRa'', C(O)RB'', C(O)NRc''Rd'', C(O)ORa'', OC(O)Rb'', OC(O)NRc''Rd'', NRc''Rd'', NRc''C(O)Rd'', NRc''C(O)ORa'', S(O)Rb'', S(O) NRc''Rd'', S(O)2Rb'', S(O)2NRc''Rd'', -(alquil C1-6)-CN, -(alquil C1-6)-ORa'', -(alquil C1-6)-SRa'', -(alquil C1-6)-C(O)Rb'', -(alquil C1-6)-C(O) NRc''Rd'', -(alquil C1-6)-C(O)ORa'', -(alquil C1-6)-OC(O)Rb'', -(alquil C1-6)-OC(O)NRc''Rd'', -(alquil C1-6)-NRc''Rd'', -(alquil C1-6)-NRc''C(O)Rd'', -(alquil C1-6)-NRc''C(O)ORa'',-(alquil C1-06)-S(O)R'', -(alquil C1-6)-S(O)NRc''Rd'', -(alquil C1-6)-S(O)2Rb'' o - (alquil C1-6)-S(O)2NRc''Rd'', donde cada uno de dichos alquilo C1-6, alquenilo C2-6, alquinilo C2-6, haloalquilo C1-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, arilalquilo, cicloalquilalquilo, heteoarilalquilo o heterocicloalquilalquilo está opcionalmente sustituido con 1, 2, 3 4 o 5 sustituyentes independientemente seleccionados a partir de: alquilo C1-6, alquenilo C2-6, alquinilo C2-6, haloalquilo C1-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, arilalquilo, cicloalquilalquilo, heteroarilalquilo, heterocicloalquilalquilo, halogeno, CN, NO2, ORa'', SRa'', C(O)Rb'', C(O) NRc''Rd'', C(O)ORa'', OC(O)Rb'', OC(O)NRc''Rd'', NRc''Rd'', NRc''Rd'', NRc''C(O)ORa'', S(O)Rb'', S(O)NRc''Rd'', S(O)2Rb'', S(O)2Rc''Rd'', -(alquil C1-6)-CN, -(alquil C1-6)-NO2, -(alquil C1-6)-ORa'', -(alquil C1-6)-SRa'', -(alquil C1-6)-C(O)Rb'', -(alquil C1-6)-C(O)NRc''Rd'', -(alquil C1-6)-C(O) ORa'', -(alquil C1-6)-OC(O)Rb'', -(alquil C1-6)-OC(O)NRc''Rd'', -(alquil C1-6)-NRc''Rd'', - (alquil C1-6)-NRc''C(O)Rd'', -(alquil C1-6)-NRc''C(O) ORa'', -(alquil C1-6)-S(O)Rb'', -alquil C1-6)-S(O)NRc''Rd'', -(alquil C1-6)-S(O)2Rb'' y -(alquil C1-6)- S(O)2NRc''Rd''; Ra, Ra' y Ra'' son cada uno independientemente, H, alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo o heterocicloalquilo; Rb, Rb'y Rb''son cada uno, independientemente, H, alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo o heterocicloalquilo; Rb, Rb' y Rb'' son cada uno, independientemente, H, alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo o heterocicloalquilo; Rc y Rd son cada uno, independientemente, H, alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, arilalquilo o cicloalquilalquilo; o Rc y Rd junto con el átomo de N atom con el cual están unidos forman un grupo heterocicloalquilo de 4-5-6 o 7 miembros; Rc' y Rd' son cada uno, independientemente, H, alquilo C1-6, haloalquilo C16, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, arilalquilo o cicloalquilalquilo; o Rc' y Rd' junto con el átomo de N atom con el cual están unidos forman un grupo heterocicloalquilo de 4-, 5-, 6-, o 7 miembros; y Rc'' y Rd'' son cada uno, independientemente, h, alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, arilalquilo o cicloalquilalquilo; o Rc'' y Rd'' junto con el átomo de N atom con el cual están unidos forman un grupo heterocicloalquilo de 4-, 5-, 6- o 7 miembros.
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US63847404P | 2004-12-22 | 2004-12-22 | |
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Families Citing this family (120)
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WO2005105814A1 (en) * | 2004-04-28 | 2005-11-10 | Incyte Corporation | Tetracyclic inhibitors of janus kinases |
TW200615268A (en) | 2004-08-02 | 2006-05-16 | Osi Pharm Inc | Aryl-amino substituted pyrrolopyrimidine multi-kinase inhibiting compounds |
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