AR058855A1 - Compuestos heterociclicos que se unen a proteinas bcl inhibiendo su funcion, composiciones farmaceuticas que los contienen y usos para el tratamiento del cancer - Google Patents

Compuestos heterociclicos que se unen a proteinas bcl inhibiendo su funcion, composiciones farmaceuticas que los contienen y usos para el tratamiento del cancer

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Publication number
AR058855A1
AR058855A1 ARP060105561A ARP060105561A AR058855A1 AR 058855 A1 AR058855 A1 AR 058855A1 AR P060105561 A ARP060105561 A AR P060105561A AR P060105561 A ARP060105561 A AR P060105561A AR 058855 A1 AR058855 A1 AR 058855A1
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AR
Argentina
Prior art keywords
independently
heteroaryl
heterocyclyl
aryl
formula
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ARP060105561A
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English (en)
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Infinity Pharmaceuticals Inc
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Publication of AR058855A1 publication Critical patent/AR058855A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/402—1-aryl substituted, e.g. piretanide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D207/12—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D207/14—Nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D233/30—Oxygen or sulfur atoms
    • C07D233/32—One oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/04—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/04—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D277/06—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms

Abstract

Reivindicacion 1: Un compuesto representado por la formula (1): o una sal farmacéuticamente aceptable del mismo; en la cual Y es -C(R10)2-, -(C=O)-, -(C=S)-, o -C(=NR10)-; X es -N(R10)- o un enlace; m es 0, 1, 2, 3, 4, 5 o 6; cada uno de A1 y A2 es independientemente H, alquilo, alquenilo, alquinilo, arilo, cicloalquilo, aralquilo, heterociclilo, heteroarilo, heteroaralquilo, -C(O)N(R10)2, -C(O)R10, -CO2R10, -S(O)2N(R10)2, -S(O)R10, -S(O)2OR10, -S(O)2R10; o tiene la formula -(C(R10)2)n-R15: en la cual, independientemente para cada ocurrencia n es 1, 2, 3, 4, 5 o 6; R15 es arilo, cicloalquilo, cicloalquenilo, heterociclilo, heteroarilo, -OR10, -SR10, -N(R10)2, -N(R10)CO2R10, -N(R10)C(O)N(R10)2, -CO2R10 o -C(O)N(R10)2; o es un anillo policíclico que contiene C8-14, del cual por lo menos uno, dos o tres átomos del anillo son independientemente S, O o N; o A1 y A2 tomados conjuntamente forman =O o =S; o A1 y A2 tomados conjuntamente con el carbono al cual están unidos forman un heterociclilo de 5 a 8 miembros, del cual uno o dos átomos del anillo son independientemente S, O o N; B es O, S, -(C=O)-, -(C=S)- o es un resto de formula (2); o tiene la formula (3): en la cual D es N o CR10; p es 0, 1, 2, 3, 4 o 5; cada uno de R7 y R8 es, independientemente para cada ocurrencia, H, alquilo, alquenilo, alquinilo, aralquilo, arilo, cicloalquilo, heterociclilo, cicloalquenilo o heteroarilo; o R7 y R8 tomados conjuntamente forman un anillo de 3-8 miembros; o R7 y R8 tomados conjuntamente forman un anillo de 4-8 miembros; R9 es H, heterociclilo, heteroarilo, -OR10, -SR10, -N(R10)2, -N(R10)CO2R10, -N(R10)C(O)N(R10)2, -CO2R10, -OCO2R10, -OC(O)N(R10)2, -C(O)N(R10)2, haluro, nitrilo, nitro o aciltio; R1 tiene la formula (4): en la cual q es 0, 1, 2, 3, 4 o 5; r es 0, 1, 2, 3, 4 o 5; Ar1 es un arilo monocíclico o bicíclico con 6-14 átomos en el anillo; o un heteroarilo monocíclico o bicíclico con 5-14 átomos en el anillo, del cual uno, dos o tresátomos del anillo son independientemente S, O o N; o Ar1 está representado por la formula (5): en la cual s es 0, 1, 2, 3 o 4; cada uno de X2 y X3 es, independientemente para cada ocurrencia, H, alquilo, alquenilo, alquinilo, arilo, cicloalquilo, heterociclilo, aralquilo, heteroarilo, heteroaralquilo, hidroxilo, aciloxi, nitrilo, nitro, haluro, OR11, -C(O)N(R10)(R11), -C(O)R11, -CO2R11, -S(O)2N(R10)(R11), SR11, -S(O)R11, -S(O)2OR11, -S(O)2R11, -C(=NR10)N(R10)(R11) o -C(=NR10)(R11); o tiene la formula - (C(R10)2)n-R15; Ar2 es un arilo monocíclico o bicíclico con 6-14 átomos en el anillo; o un heteroarilo monocíclico o bicíclico con 5-14 átomos en el anillo, del cual uno, dos o tres átomos del anillo son independientemente S, O o N; X1 es un enlace, -C(R10)2-, -S-, -(NR10)- o -O-; R2 es H, un alquilo o alquenilo ramificado o no ramificado, cicloalquilo, heterociclilo o bicicloalquilo; o tiene la formula -(C(R10)2)n-R15; R3 es H, heterociclilo, heteroarilo, -OR10, -SR10, -N(R10)2, -N(R10)CO2R10, -N(R10)C(O)N(R10)2, -CO2R10, -OCO2R10, -OC(O)N(R10)2, -C(O)N(R10)2, haluro, nitrilo, nitro o aciltio; cada uno de R4, R5 y R10, independientemente para cada ocurrencia, es H, alquilo, alquenilo, alquinilo, aralquilo, arilo, cicloalquilo, cicloalquenilo, bicicloalquilo, heterociclilo o heteroarilo; o tiene la formula -(C(R10)2)n-R15; o cualesquiera dos casos de R10 tomados conjuntamente forman un anillo de 3-8 miembros; o R4 y R5 tomados conjuntamente forman un anillo de 3-8 miembros; R6 es H o alquilo; R11 es, independientemente para cada ocurrencia, H, alquilo, alquenilo, alquinilo, aralquilo, arilo, cicloalquilo, cicloalquenilo, bicicloalquilo, heterociclilo, heteroarilo o -[C(R12)(R13)]t-R14; en donde t es 0, 1, 2, 3, 4 o 5; cada uno de R12 y R13 es independientemente para cada ocurrencia, H, alquilo, arilo, aralquilo, cicloalquilo, heterociclilo, heterociclilalquilo, heteroarilo o heteroaralquilo; yR14 es independientemente para cada ocurrencia, H, alquilo, arilo, heteroarilo, heterociclilalquilo, alcoxi, amino, amido, o carboxilo.
ARP060105561A 2005-12-16 2006-12-15 Compuestos heterociclicos que se unen a proteinas bcl inhibiendo su funcion, composiciones farmaceuticas que los contienen y usos para el tratamiento del cancer AR058855A1 (es)

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US (2) US7745464B2 (es)
EP (1) EP1973875B1 (es)
JP (1) JP5341521B2 (es)
KR (1) KR101373911B1 (es)
CN (1) CN101374807B (es)
AR (1) AR058855A1 (es)
AU (1) AU2006329879B2 (es)
BR (1) BRPI0619968A2 (es)
CA (1) CA2633958C (es)
EC (1) ECSP088607A (es)
ES (1) ES2494765T3 (es)
HK (1) HK1119704A1 (es)
IL (1) IL192023A (es)
JO (1) JO2918B1 (es)
MA (1) MA30144B1 (es)
MX (1) MX2008007687A (es)
MY (1) MY153232A (es)
NO (1) NO20083050L (es)
NZ (1) NZ569660A (es)
PE (1) PE20071033A1 (es)
RU (1) RU2424230C2 (es)
SA (1) SA06270462B1 (es)
SG (1) SG170727A1 (es)
TN (1) TNSN08258A1 (es)
TW (1) TWI403320B (es)
WO (1) WO2007075387A1 (es)
ZA (1) ZA200805822B (es)

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TWI403320B (zh) 2013-08-01
US7745464B2 (en) 2010-06-29
EP1973875A1 (en) 2008-10-01
KR101373911B1 (ko) 2014-03-12
ZA200805822B (en) 2009-03-25
US20070155705A1 (en) 2007-07-05
AU2006329879B2 (en) 2012-06-21
CA2633958C (en) 2014-04-01
WO2007075387A1 (en) 2007-07-05
NO20083050L (no) 2008-09-10
TW200811100A (en) 2008-03-01
SA06270462B1 (ar) 2011-10-03
TNSN08258A1 (en) 2009-10-30
ES2494765T3 (es) 2014-09-16
BRPI0619968A2 (pt) 2011-10-25
MY153232A (en) 2015-01-29
KR20080077017A (ko) 2008-08-20
HK1119704A1 (en) 2009-03-13
PE20071033A1 (es) 2007-11-26
CN101374807B (zh) 2013-10-09
JO2918B1 (en) 2015-09-15
ECSP088607A (es) 2008-08-29
AU2006329879A8 (en) 2008-08-07
AU2006329879A1 (en) 2007-07-05
US8304428B2 (en) 2012-11-06
EP1973875B1 (en) 2014-06-11
CN101374807A (zh) 2009-02-25
IL192023A0 (en) 2008-12-29
CA2633958A1 (en) 2007-07-05
JP2009519946A (ja) 2009-05-21
US20100190791A1 (en) 2010-07-29
JP5341521B2 (ja) 2013-11-13
MX2008007687A (es) 2008-09-26
RU2008128569A (ru) 2010-01-27
MA30144B1 (fr) 2009-01-02
NZ569660A (en) 2010-07-30
RU2424230C2 (ru) 2011-07-20
IL192023A (en) 2014-06-30
SG170727A1 (en) 2011-05-30

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