AR083855A1 - Inhibidores de nampt y rock - Google Patents
Inhibidores de nampt y rockInfo
- Publication number
- AR083855A1 AR083855A1 ARP110104229A ARP110104229A AR083855A1 AR 083855 A1 AR083855 A1 AR 083855A1 AR P110104229 A ARP110104229 A AR P110104229A AR P110104229 A ARP110104229 A AR P110104229A AR 083855 A1 AR083855 A1 AR 083855A1
- Authority
- AR
- Argentina
- Prior art keywords
- nhc
- independently selected
- alkynyl
- alkenyl
- alkyl
- Prior art date
Links
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
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- 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
- A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
- A61K31/4035—Isoindoles, e.g. phthalimide
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
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- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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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
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Abstract
Compuestos que inhiben la actividad de la NAMPT, composiciones que contienen los compuestos y métodos para tratar enfermedades en las cuales se expresa la NAMPT. Compuestos que inhiben la actividad de la ROCK, composiciones que contienen los compuestos y métodos para tratar enfermedades en las cuales se expresa la ROCK.Reivindicación 1: Un compuesto caracterizado porque es de fórmula (1), y sus sales farmacéuticamente aceptables, donde X1, X2, y X3 son CH; o X1 y X3 son CH; y X2 es N; o X1 y X3 son CH; y X2 es CR1; o X2 y X3 son CH; y X1 es CR1; o X1 es CH; y X2 y X3 son CR1; o X2 es CH; y X1 y X3 son N; o X2 y X3 son CH; y X1 es N; o X1 es CH; X2 es N; y X3 es CR1; o X1 es CR1; X2 es N; y X3 es CH; o X1 es N; X2 es CR1; y X3 es CH; o X1 es N; X2 es CR1; y X3 es N; R1 es R3, OR3, SR3, S(O)R3, SO2R3, C(O)R3, C(O)OR3, OC(O)R3, NHR3, N(R3)2, C(O)NH2, C(O)NHR3, C(O)N(R3)2, NHC(O)R3, NR3C(O)R3, NHC(O)OR3, NR3C(O)OR3, SO2NH2, SO2NHR3, SO2N(R3)2, NHSO2R3, NR3SO2R3, NHSO2NHR3, NHSO2N(R3)2, NR3SO2NHR3, NR3SO2N(R3)2, C(O)NHSO2R3, NHSO2NHR3, F, Cl, Br, I, CN, NH2, NO2, N3, OH, C(O)H, CF3, C(O)OH, o C(O)NH2; R2 es alquilo, alquenilo, alquinilo, fenilo, heterociclilo, cicloalquilo, o cicloalquenilo; donde cada R2 alquilo, alquenilo, y alquinilo se sustituye opcionalmente con uno, dos, tres o cuatro sustituyentes seleccionados en forma independiente entre R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br o I; donde cada R2 fenilo se sustituye opcionalmente en la posición para con un sustituyente seleccionado en forma independiente entre R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, CHNOR5, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, OH, CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, Br o I; donde cada R2 fenilo está además opcionalmente sustituido con un F; donde cada R2 heterociclilo, cicloalquilo, y cicloalquenilo se sustituye opcionalmente con uno, dos, tres o cuatro sustituyentes seleccionados en forma independiente entre R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, OH, CN, N3, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br o I; R3, en cada caso, es un sustituyente seleccionado en forma independiente entre alquilo, alquenilo, alquinilo, arilo, o heterociclilo; donde cada R3 alquilo, alquenilo, y alquinilo se sustituye opcionalmente con uno, dos, tres o cuatro sustituyentes seleccionados en forma independiente entre R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br o I; R4, en cada caso, es un sustituyente seleccionado en forma independiente entre alquilo, alquenilo, alquinilo, arilo, cicloalquilo, o heterociclilo; donde cada R4 alquilo, alquenilo, y alquinilo se sustituye opcionalmente con uno, dos, tres o cuatro sustituyentes seleccionados en forma independiente entre R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br o I; donde cada R4 arilo y heterociclilo se sustituye opcionalmente con uno, dos, tres o cuatro sustituyentes seleccionados en forma independiente entre R8 , OR8 , SR8, S(O)R8, SO2R8 , C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, OH, CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br o I; R5, en cada caso, es un sustituyente seleccionado en forma independiente entre alquilo, alquenilo, alquinilo, arilo, heterociclilo, cicloalquilo, o cicloalquenilo; donde cada R5 alquilo, alquenilo, y alquinilo se sustituye opcionalmente con uno, dos, tres o cuatro sustituyentes seleccionados en forma independiente entre R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br o I; R6, en cada caso, es un sustituyente seleccionado en forma independiente entre alquilo, alquenilo, alquinilo, arilo, heterociclilo, cicloalquilo, o cicloalquenilo; donde cada R6 alquilo, alquenilo, y alquinilo se sustituye opcionalmente con uno, dos, tres o cuatro sustituyentes seleccionados en forma independiente entre R10, OR10, SR10, S(O)R10, SO2R10, NHR10, N(R10)2, C(O)R10, C(O)NH2, C(O)NHR10, C(O)N(R10)2, NHC(O)R10, NR10C(O)R10, NHSO2R10, NHC(O)OR10, SO2NH2, SO2NHR10, SO2N(R10)2, NHC(O)NH2, NHC(O)NHR10, OH, (O), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br o I; R7, en cada caso, es un sustituyente seleccionado en forma independiente entre alquilo, alquenilo, alquinilo, arilo, heterociclilo, cicloalquilo, o cicloalquenilo; donde cada R7 alquilo, alquenilo, y alquinilo se sustituye opcionalmente con uno, dos, tres o cuatro sustituyentes seleccionados en forma independiente entre R11, OR11, SR11, S(O)R11, SO2R11, NHR11, N(R11)2, C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, NHC(O)R11, NR11C(O)R11, NHSO2R11, NHC(O)OR11, SO2NH2, SO2NHR11, SO2N(R11)2, NHC(O)NH2, NHC(O)NHR11, OH, (O), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br o I; R8 en cada caso, es un sustituyente seleccionado en forma independiente entre alquilo, alquenilo, alquinilo, arilo, heterociclilo, cicloalquilo, o cicloalquenilo; donde cada R8 alquilo, alquenilo, y alquinilo se sustituye opcionalmente con uno, dos, tres o cuatro sustituyentes seleccionados en forma independiente entre R12, OR12, SR12, S(O)R12, SO2R12, NHR12, N(R12)2, C(O)R12, C(O)NH2, C(O)NHR12, C(O)N(R12)2, NHC(O)R12, NR12C(O)R12 NHSO2R12, NHC(O)OR12, SO2NH2, SO2NHR12, SO2N(R12)2, NHC(O)NH2, NHC(O)NHR12, OH, (O), C(O)OH, N3, CN, NH2, CF3, CF2CF3, F, Cl, Br o I; R9, en cada caso, es un sustituyente seleccionado en forma independiente entre alquilo, alquenilo, alquinilo, arilo, heterociclilo, cicloalquilo, o cicloalquenilo; donde cada R9 alquilo, alquenilo, y alquinilo se sustituye opcionalmente con uno, dos, tres o cuatro sustituyentes seleccionados en forma independiente entre alcoxi, OH, cicloalquilo, arilo, o heterociclilo; R10, en cada caso, es un sustituyente seleccionado en forma independiente entre alquilo, alquenilo, alquinilo, arilo, heterociclilo, cicloalquilo, o cicloalquenilo; R11, en cada caso, es un sustituyente seleccionado en forma independiente entre alquilo, alquenilo, alquinilo, arilo, heterociclilo, cicloalquilo, o cicloalquenilo; R12, en cada caso, es un sustituyente seleccionado en forma independiente entre alquilo, alquenilo, alquinilo, arilo, heterociclilo, cicloalquilo, o cicloalquenilo; donde cada R12 alquilo, alquenilo, y alquinilo se sustituye opcionalmente con uno o más alcoxi; donde las unidades cíclicas representadas por R3, R5, R6, R7, R8, R9, R10, R11, y R12 se sustituyen opcionalmente con uno, dos, tres, cuatro, cinco o seis sustituyentes seleccionados en forma independiente entre R13, OR13, SR13, S(O)R13, SO2R13, C(O)R13, CO(O)R13, OC(O)R13, OC(O)OR13, NH2, NHR13, N(R13)2, NHC(O)R13, NR13C(O)R13, NHS(O)2R13, NR13S(O)2R13, NHC(O)OR13, NR13C(O)OR13, NHC(O)NH2, NHC(O)NHR13, NHC(O)N(R13)2, NR13C(O)NHR13, NR13C(O)N(R13)2, C(O)NH2, C(O)NHR13, C(O)N(R13)2, C(O)NHOH, C(O)NHOR13, C(O)NHSO2R13, C(O)NR13SO2R13, SO2NH2, SO2NHR13, SO2N(R13)2, C(O)H, C(O)OH, OH, CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, Cl, Br o I; R13, en cada caso, es un sustituyente seleccionado en forma independiente entre alquilo, alquenilo, alquinilo, arilo, tetrahidrofuranilo, piridazinilo, pirazinilo, pirimidinilo, piridinilo, tieno[3,2-c]piridinilo, furo[3,2-c]piridinilo, pirrolidin-2-onilo, 1,1-dioxidotetrahidrotien-3-ilo, 1,1-dioxidotetrahidro-2H-tiopiran-3-ilo, dioxanilo, tetrahidropiranilo, piperidinilo, pirimidinilo, oxazolilo, pirazolilo, tiazolilo, pirrolidinilo, pirrolilo, tienilo, furanilo, morfolinilo, isooxazolilo, cicloalquilo, o cicloalquenilo; donde cada R13 alquilo, alquenilo, y alquinilo se sustituye opcionalmente con uno, dos, tres o cuatro sustituyentes seleccionados en forma independiente entre R14, OR14, SR14, S(O)R14, SO2R14, C(O)R14, OC(O)R14, OC(O)OR14, NH2, NHR14, N(R14)2, NHC(O)R14, NR14C(O)R14, NHS(O)2R14, NR14S(O)2R14, NHC(O)OR14, NR14C(O)OR14, NHC(O)NH2, NHC(O)NHR14, NHC(O)N(R14)2, NR14C(O)NHR14, NR14C(O)N(R14)2, C(O)NH2, C(O)NHR14, C(O)N(R14)2, C(O)NHOH, C(O)NHOR14, C(O)NHSO2R14, C(O)NR14SO2R14, SO2NH2, SO2NHR14, SO2N(R14)2, C(O)H, C(O)OH, OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br o I; donde cada R13 a
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GB201021103D0 (en) * | 2010-12-13 | 2011-01-26 | Univ Leuven Kath | New compounds for the treatment of neurodegenerative diseases |
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- 2011-11-11 RU RU2013126657/04A patent/RU2013126657A/ru not_active Application Discontinuation
- 2011-11-11 US US13/294,303 patent/US9302989B2/en active Active
- 2011-11-11 KR KR1020137015348A patent/KR20140009251A/ko not_active Application Discontinuation
- 2011-11-11 EP EP11787996.5A patent/EP2640698A1/en not_active Withdrawn
-
2013
- 2013-04-21 IL IL225862A patent/IL225862A0/en unknown
- 2013-05-14 DO DO2013000106A patent/DOP2013000106A/es unknown
- 2013-05-14 CL CL2013001340A patent/CL2013001340A1/es unknown
- 2013-05-14 GT GT201300124A patent/GT201300124A/es unknown
- 2013-06-07 CR CR20130267A patent/CR20130267A/es unknown
- 2013-06-13 EC ECSP13012993 patent/ECSP13012993A/es unknown
- 2013-06-14 CO CO13143136A patent/CO6761389A2/es unknown
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2015
- 2015-10-12 US US14/880,834 patent/US10093624B2/en active Active
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2017
- 2017-01-06 AU AU2017200079A patent/AU2017200079A1/en not_active Abandoned
- 2017-03-22 JP JP2017055914A patent/JP2017132792A/ja active Pending
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EP2640698A1 (en) | 2013-09-25 |
SG10202010119TA (en) | 2020-11-27 |
JP2017132792A (ja) | 2017-08-03 |
WO2012067965A1 (en) | 2012-05-24 |
IL225862A0 (en) | 2013-06-27 |
KR20140009251A (ko) | 2014-01-22 |
AU2011329233A1 (en) | 2013-05-23 |
US9302989B2 (en) | 2016-04-05 |
JP6117104B2 (ja) | 2017-04-19 |
AU2017200079A1 (en) | 2017-02-02 |
SG10201602857UA (en) | 2016-05-30 |
SG190819A1 (en) | 2013-07-31 |
CO6761389A2 (es) | 2013-09-30 |
CL2013001340A1 (es) | 2013-09-06 |
BR112013012078A2 (pt) | 2019-09-24 |
CN103313968A (zh) | 2013-09-18 |
US10093624B2 (en) | 2018-10-09 |
US20120122842A1 (en) | 2012-05-17 |
US20160031880A1 (en) | 2016-02-04 |
GT201300124A (es) | 2014-12-12 |
PE20140913A1 (es) | 2014-08-22 |
MX2013005454A (es) | 2013-06-24 |
RU2013126657A (ru) | 2014-12-27 |
ECSP13012993A (es) | 2014-01-31 |
TW201238950A (en) | 2012-10-01 |
DOP2013000106A (es) | 2013-10-15 |
CA2816594A1 (en) | 2012-05-24 |
JP2013542265A (ja) | 2013-11-21 |
UY33726A (es) | 2012-06-29 |
CR20130267A (es) | 2013-10-04 |
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