AR064155A1 - Compuestos de inhibidores de fosfoinositido-3 quinasa y metodos de uso - Google Patents
Compuestos de inhibidores de fosfoinositido-3 quinasa y metodos de usoInfo
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- AR064155A1 AR064155A1 ARP070105449A ARP070105449A AR064155A1 AR 064155 A1 AR064155 A1 AR 064155A1 AR P070105449 A ARP070105449 A AR P070105449A AR P070105449 A ARP070105449 A AR P070105449A AR 064155 A1 AR064155 A1 AR 064155A1
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- group
- alkyl
- optionally substituted
- nr10r11
- cr14r15
- Prior art date
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- 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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- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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- 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
Son utiles para modular la actividad de lipidoquinasas que incluyen PI3K, y para tratar trastornos tales como cáncer mediado por lipidoquinasas. Se describen métodos para usar compuestos de las formulas 1a-d para el diagnostico, la prevencion o el tratamiento in vitro, in situ e in vivo de dichos trastornos en células de mamíferos, o condiciones patologicas asociadas. Reivindicacion 1: Un compuesto seleccionado de las formulas 1c y 1d, y sus estereoisomeros, isomeros geométricos, tautomeros, solvatos, metabolitos y sales farmacéuticamente aceptables, en donde: X es O o S; R1 es un grupo de la formula: (R4)(R5)N-(CHR30)m-; R2 está seleccionado de H, F, CI, Br, I, arilo C6-20, heteroarilo C1-20, alquilo C1-6, alquenilo C2-8, y alquinilo C2-8; R3 es un grupo heteroarilo monocíclico seleccionado de piridilo, isoxazolilo, imidazolilo, pirazolilo, pirrolilo, tiazolilo, piridazinilo, pirimidinilo, pirazinilo, oxazolilo, furanilo, tienilo, triazolilo, tetrazolilo, donde el grupo heteroarilo monocíclico está opcionalmente sustituido con uno o varios grupos seleccionados de F, CI, Br, I, -CN, -NR10R11, -OR10, -C(O)R10, -NR10C(O)R11, -N(C(O)R11)2, -NR10C(O)NR10R11, -C(=O)OR10, -C(=O)NR10R11, alquilo C1-12 y alquil C1-12- OR10; R4 y R5 forman, junto con el átomo de N al que están unidos, un grupo seleccionado de piperazina, piperidina, pirrolidina, oxazolidinona, morfolina, tiomorfolina, diazepan y 2,5-diaza-biciclo[2,2,1]-heptano, cuyo grupo está opcionalmente sustituido con uno o varios grupos seleccionados, de modo independiente, de F, CI, Br, I, -CN, CF3, -NO2, oxo,-C(=Y)R10, -C(=Y)OR10, -C(=Y)NR10R11, -(CR14R15)nNR10R11, -(CR14R15)nNR12SO2R10, -(CR14R15)nOR10, -NR10R11, -NR12C(=Y)R10, -NR12C(=Y)OR11, - NR12C(=Y)NR10R11, -NR12SO2R10, =NR12, OR10, OC(=Y)R10, -OC(=Y)OR10, -OC(=Y)NR10R11, -OS(O)2(OR10), -OP(=Y)(OR10)(OR11), -OP(OR10)(OR11), SR10, -S(O)R10, -S(O)2-alquil C1-6-S(O)2R10, -S(O)2R10, -S(O)2NR10R11, -S(O)(OR10), -S(O)2(OR10), -SC(=Y)R10, SC(=Y)OR10, -SC(=Y)NR10R11, alquilo C1-12 opcionalmente sustituido, alquenilo C2-8 opcionalmente sustituido, alquinilo C2-8 opcionalmente sustituido, carbociclilo C3-12 opcionalmente sustituido, heterociclilo C2-20 opcionalmente sustituido, arilo C6- 20 opcionalmente sustituido, y heteroarilo C1-20 opcionalmente sustituido; o uno de R4 y R5 es alquilo C1-6, -(alquil C1-6)q-heterociclilo C2-20, o -(alquil C1-6)q-OR10 y el otro es un grupo piperazina, piperidina, pirrolidina, sulfonilpirano, - (alk)q-heterociclilo C2-20 o un grupo -(alk)q-heteroarilo C1-20, en donde dicho grupo piperazina, piperidina, pirrolidina, sulfonilpirano, heterociclilo o heteroarilo no está sustituido o está sustituido con alquilo C1-6, -(alquil C1-6)q-OR10 o - S(O)2R10; R10, R11, R12 son, de modo independiente, H, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, carbociclilo C3-12, heterociclilo C2-20, arilo C6-20 o heteroarilo C1-20, o R10 y R11 junto con el nitrogeno al que están unidos, forman un anillo heterocíclico C3-20 que opcionalmente contiene uno o varios átomos de anillo adicionales seleccionados de N, O o S, en donde dicho anillo heterocíclico está opcionalmente sustituido con uno o varios grupos seleccionados, de modo independiente, de oxo, (CH2)nOR10, NR10R11, CF3, F, CI, Br, I, SO2R10, C(=O)R10, NR12C(=Y)R11, C(=Y)NR10R11, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, carbociclilo C3-12, heterociclilo C2-20, arilo C6-20 y heteroarilo C1-20; R14 y R15 están seleccionados, de modo independiente, de H, alquilo C1-12, o -(CH2)n-arilo, o R14 y R15 junto con los átomos a los que están unidos, forman un anillo carbocíclico C3-12 saturado o parcialmente insaturado, R30 es H o alquilo C1-6; mor es un grupo morfolina opcionalmente sustituido con uno o varios grupos seleccionados de F, CI, Br, I, -C(alquil C1-6)2NR10R11, -(CR14R15)tNR10R11, -C(R14R15)nNR12C(=Y)R10, --(CR14R15)nNR12SO2R10, CH(OR10)R10, -(CR14R15)nOR10, -(CR14R15)nS(O)2R10, -(CR14R15)S(O)2NR10R11, - C(=Y)R10, -C(=Y)OR10, -C(=Y)NR10R11, -C(=Y)NR12OR10, -C(=O)NR12S(O)2R10, -C(=O)NR12(CR14R15)mNR10R11, -NO2, -NHR12, -NR12C(=Y)R11, -NR12C(=Y)OR11, -NR12C(=Y)NR10R11, -NR12S(O)2R10, -NR12SO2NR10R11, -S(O)2R10, -S(O)2NR10R11, -SC(=Y)R10, -SC(=Y)OR10, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, carbociclilo C3-12, heterociclilo C2-20, arilo C6-20 o heteroarilo C1-20; donde dicho alquilo, alquenilo, alquinilo, carbociclilo, heterociclilo, arilo y heteroarilo están opcionalmente sustituidos con uno o varios grupos seleccionados, de modo independiente, de F, CI, Br, I, -CN, CF3, -NO2, oxo, -C(=Y)R10, -C(=Y)OR10, -C(=Y)NR10R11, -(CR14R15)nNR10R11, -(CR14R15)nNR12SO2R10, -(CR14R15)nOR10, -NR10R11, -NR12C(=Y)R10, -NR12C(=Y)OR11, - NR12C(=Y)NR10R11, -NR12SO2R10, =NR12, OR10, OC(=Y)R10, -OC(=Y)OR10, -OC(=Y)NR10R11, -OS(O)2(OR10), -OP(=Y)(OR10)(OR11), -OP(OR10)(OR11), SR10, -S(O)R10, -S(O)2R10, -S(O)2NR10R11, -S(O)(OR10), -S(O)2(OR10), -SC(=Y)R10, SC(=Y)OR10, -SC(=Y)NR10R11, alquilo C1-12 opcionalmente sustituido, alquenilo C2-8 opcionalmente sustituido, alquinilo C2-8 opcionalmente sustituido, carbociclilo C3-12 opcionalmente sustituido, heterociclilo C2-20 opcionalmente sustituido, arilo C6-20 opcionalmente sustituido, y heteroarilo C1-20 opcionalmente sustituido; Y es O, S o NR12; cada q es, de modo independiente, 0 o 1; m es 0 o 1; y r es 0 o 1; con la condicion de que: (i) cuando en la formula (1c) mor es morfolino no sustituido, X es S, R1 es un grupo (4-metilsulfonilpiperazin-1-iI)metilo y R2 es H, entonces R3 no sea un grupo seleccionado de imidazolilo que no está sustituido o que está sustituido con un grupo CH3, pirimidinilo que no está sustituido y piridinil que no está sustituido o que está sustituido con un grupo F; (ii) cuando en la formula (1c) mor es morfolino no sustituido, X es S, R1 es un grupo (4-metilpiperazin-1-il)metilo y R2 es H, entonces R3 no sea un grupo seleccionado de pirazolilo que no está sustituido y piridinilo que está sustituido con un grupo OH; y (iii) cuando en la formula (1d) mor es morfolino no sustituido, X es S, R1 es un grupo (4-metilsulfonilpiperazin-1-il)metilo y R2 es H, entonces R3 no sea un grupo seleccionado de piridinilo que no está sustituido y pirimidinilo que no está sustituido o que está sustituido con un grupo -OCH3 o -N(CH3)2.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US87344806P | 2006-12-07 | 2006-12-07 | |
US97725707P | 2007-10-03 | 2007-10-03 |
Publications (1)
Publication Number | Publication Date |
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AR064155A1 true AR064155A1 (es) | 2009-03-18 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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ARP070105449A AR064155A1 (es) | 2006-12-07 | 2007-12-05 | Compuestos de inhibidores de fosfoinositido-3 quinasa y metodos de uso |
Country Status (22)
Country | Link |
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US (3) | US7888352B2 (es) |
EP (2) | EP2114949A1 (es) |
JP (1) | JP5284977B2 (es) |
KR (1) | KR101460816B1 (es) |
AR (1) | AR064155A1 (es) |
AU (1) | AU2007329352B2 (es) |
BR (1) | BRPI0717923A2 (es) |
CA (1) | CA2671782C (es) |
CL (1) | CL2007003520A1 (es) |
CO (1) | CO6190615A2 (es) |
CR (1) | CR10915A (es) |
EC (1) | ECSP099496A (es) |
ES (1) | ES2544082T3 (es) |
MA (1) | MA31146B1 (es) |
MX (1) | MX2009005950A (es) |
MY (1) | MY180595A (es) |
NO (1) | NO20092566L (es) |
NZ (1) | NZ578162A (es) |
PE (1) | PE20081679A1 (es) |
RU (1) | RU2468027C2 (es) |
TW (1) | TWI499420B (es) |
WO (1) | WO2008070740A1 (es) |
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RU2439074C2 (ru) | 2006-04-26 | 2012-01-10 | Ф. Хоффманн-Ля Рош Аг | ПРОИЗВОДНОЕ ТИЕНО[3,2-d]ПИРИМИДИНА В КАЧЕСТВЕ ИНГИБИТОРА ФОСФАТИДИЛИНОЗИТОЛ-3-КИНАЗЫ (РI3К) |
MX2008013583A (es) * | 2006-04-26 | 2008-10-31 | Genentech Inc | Compuestos del inhibidor de fosfoinositido 3-cinasa y composiciones farmaceuticas que los contienen. |
GB0608820D0 (en) | 2006-05-04 | 2006-06-14 | Piramed Ltd | Pharmaceutical compounds |
KR101507182B1 (ko) | 2006-12-07 | 2015-03-30 | 제넨테크, 인크. | 포스포이노시타이드 3-키나제 억제제 화합물 및 그의 사용 방법 |
ES2544082T3 (es) | 2006-12-07 | 2015-08-27 | F. Hoffmann-La Roche Ag | Compuestos inhibidores de fosfoinosítido 3-quinasa y métodos de uso |
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