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AR099466A1 - Prolinas / piperidinas sustituidas como antagonistas del receptor de orexina - Google Patents

Prolinas / piperidinas sustituidas como antagonistas del receptor de orexina

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Publication number
AR099466A1
AR099466A1 ARP150100403A ARP150100403A AR099466A1 AR 099466 A1 AR099466 A1 AR 099466A1 AR P150100403 A ARP150100403 A AR P150100403A AR P150100403 A ARP150100403 A AR P150100403A AR 099466 A1 AR099466 A1 AR 099466A1
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AR
Argentina
Prior art keywords
group
optionally substituted
methyl
independently selected
disorder
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Application number
ARP150100403A
Other languages
English (en)
Inventor
Nguyen William
Song Xinyi
Jason Herr Robert
Barnes Keith
D Young Steven
Jiang Qin
M Kamenecka Theodore
He Yuanjun
Jiang Rong
Original Assignee
Eolas Therapeutics Inc
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Filing date
Publication date
Application filed by Eolas Therapeutics Inc filed Critical Eolas Therapeutics Inc
Publication of AR099466A1 publication Critical patent/AR099466A1/es

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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
    • C07D471/08—Bridged systems
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    • 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
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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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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Abstract

La presente hace referencia a compuestos que modulan la bioactividad de un receptor de orexina como por ejemplo OX₁ o OX₂, o ambos; a composiciones farmacéuticas y combinaciones que comprenden un compuesto de la presente; a métodos de tratamiento de afecciones en pacientes para las cuales se indica médicamente la modulación de un receptor de orexina; y a métodos de preparación de compuestos de la presente. Por ejemplo, los compuestos moduladores del receptor de orexina de la presente pueden usarse en el tratamiento de un trastorno de la alimentación, obesidad, alcoholismo o un trastorno relacionado con el alcohol, abuso de sustancias o adicción a las mismas incluyendo adicción a cocaína, opiáceos, anfetaminas o nicotina, un trastorno del sueño, una disfunción cognitiva en un trastorno psiquiátrico o neurológico, depresión, ansiedad, trastorno de estrés postraumático, trastorno afectivo estacional, un trastorno de la alimentación, trastorno de pánico, esquizofrenia, enfermedad de Alzheimer, enfermedad de Parkinson, corea de Huntington, dolor de cabeza, migraña, dolor, enfermedades gastrointestinales, epilepsia, inflamaciones, enfermedades relacionadas con el sistema inmune, enfermedades relacionadas con el sistema endocrino, cáncer, hipertensión, trastornos del comportamiento, trastornos anímicos, depresión con manía, demencia, trastornos sexuales, trastornos psicosexuales, o enfermedad renal. Reivindicación 1: Un compuesto caracterizado porque es de fórmula (1) donde R¹⁰ es H o metilo; Het² se selecciona entre el grupo que consiste en pirrolilo, pirazolilo, imidazolilo, oxazolilo, isoxazolilo, tiazolilo, isotiazolilo, oxadiazolilo, tiadiazolilo, triazolilo, tetrazolilo, piridilo, pirimidinilo, piridazinilo y pirazinilo; donde Het² está opcionalmente sustituido con uno, dos o tres sustituyentes seleccionados en forma independiente entre el grupo que consiste en halo, C₁₋₄alquilo, C₁₋₄alcoxi, -CN, -CF₃, y C₃₋₆cicloalquilo, donde dicho cicloalquilo está opcionalmente sustituido con halo, metilo, o ciano; o dos sustituyentes adyacentes tomados junto con los átomos a los que están unidos forman un fenilo fusionado o heteroarilo monocíclico; X, Y, y Z se definen como en (a), (b), o (c), donde: (a) X es N, Y es CH, y Z es S; (b) X es N, Y es CHCH, y Z es CH; y (c) X es CH, Y es CHCH, y Z es CH; donde los grupos CH están opcionalmente sustituidos con B y (R¹¹)ₜ como se muestra; cada R¹¹ se selecciona en forma independiente entre el grupo que consiste en metilo, ciano, cloro, fluoro, y metoxi; t es 0, 1, ó 2; y B se selecciona entre el grupo que consiste en fenilo, pirrolilo, pirazolilo, imidazolilo, oxazolilo, isoxazolilo, tiazolilo, isotiazolilo, oxadiazolilo, tiadiazolilo, triazolilo, tetrazolilo, piridilo, pirimidinilo, piridazinilo y pirazinilo, cada uno de ellos opcionalmente sustituido con uno o dos sustituyentes Rʸ; en donde Rʸ se selecciona en forma independiente entre el grupo que consiste en metilo, etilo, propilo, isopropilo, butilo, isobutilo, metoxi, etoxi, isopropoxi, -F, -Cl, -Br, -CN, y CF₃; o una sal farmacéuticamente aceptable del mismo; siempre que el compuesto no sea de fórmula (2); o un compuesto de fórmula (3) donde R¹⁰ es H o metilo; Het² se selecciona entre el grupo que consiste en pirrolilo, pirazolilo, imidazolilo, oxazolilo, isoxazolilo, tiazolilo, isotiazolilo, oxadiazolilo, tiadiazolilo, triazolilo, tetrazolilo, piridilo, pirimidinilo, piridazinilo y pirazinilo; donde Het² está opcionalmente sustituido con uno, dos o tres sustituyentes seleccionados en forma independiente entre el grupo que consiste en halo, C₁₋₄alquilo, C₁₋₄alcoxi, -CN, -CF₃, y C₃₋₆cicloalquilo, donde dicho cicloalquilo está opcionalmente sustituido con halo, metilo, o ciano; o dos sustituyentes adyacentes tomados junto con los átomos a los que están unidos forman un fenilo fusionado o heteroarilo monocíclico; X, Y, y Z se definen como en (a), (b), o (c), donde: (a) X es N, Y es CH, y Z es S; (b) X es N, Y es CHCH, y Z es CH; y (c) X es CH, Y es CHCH, y Z es CH; donde los grupos CH están opcionalmente sustituidos con B y (R¹¹)ₜ como se muestra; cada R¹¹ se selecciona en forma independiente entre el grupo que consiste en metilo, ciano, cloro, fluoro, y metoxi; t es 0, 1, ó 2; y B se selecciona entre el grupo que consiste en fenilo, pirrolilo, pirazolilo, imidazolilo, oxazolilo, isoxazolilo, tiazolilo, isotiazolilo, oxadiazolilo, tiadiazolilo, triazolilo, tetrazolilo, piridilo, pirimidinilo, piridazinilo y pirazinilo, cada uno de ellos opcionalmente sustituido con uno o dos sustituyentes Rʸ; en donde Rʸ se selecciona en forma independiente entre el grupo que consiste en metilo, etilo, propilo, isopropilo, butilo, isobutilo, metoxi, etoxi, isopropoxi, -F, -Cl, -Br, -CN, y CF₃; o una sal farmacéuticamente aceptable del mismo; o un compuesto de fórmula (4) donde Het² se selecciona entre el grupo que consiste en pirrolilo, pirazolilo, imidazolilo, oxazolilo, isoxazolilo, tiazolilo, isotiazolilo, oxadiazolilo, tiadiazolilo, triazolilo, tetrazolilo, piridilo, pirimidinilo, piridazinilo y pirazinilo; donde Het² está opcionalmente sustituido con uno, dos o tres sustituyentes seleccionados en forma independiente entre el grupo que consiste en halo, C₁₋₄alquilo, C₁₋₄alcoxi, -CN, -CF₃, y C₃₋₆cicloalquilo, donde dicho cicloalquilo está opcionalmente sustituido con halo, metilo, o ciano; o dos sustituyentes adyacentes tomados junto con los átomos a los que están unidos forman un fenilo fusionado o heteroarilo monocíclico; X, Y, y Z se definen como en (a), (b), o (c), donde: (a) X es N, Y es CH, y Z es S; (b) X es N, Y es CHCH, y Z es CH; y (c) X es CH, Y es CHCH, y Z es CH; donde los grupos CH están opcionalmente sustituidos con B y (R¹¹)ₜ como se muestra; cada R¹¹ se selecciona en forma independiente entre el grupo que consiste en metilo, ciano, cloro, fluoro, y metoxi; t es 0, 1, ó 2; y B se selecciona entre el grupo que consiste en fenilo, pirrolilo, pirazolilo, imidazolilo, oxazolilo, isoxazolilo, tiazolilo, isotiazolilo, oxadiazolilo, tiadiazolilo, triazolilo, tetrazolilo, piridilo, pirimidinilo, piridazinilo y pirazinilo, cada uno de ellos opcionalmente sustituido con uno o dos sustituyentes Rʸ; en donde Rʸ se selecciona en forma independiente entre el grupo que consiste en metilo, etilo, propilo, isopropilo, butilo, isobutilo, metoxi, etoxi, isopropoxi, -F, -Cl, -Br, -CN, y CF₃; o una sal farmacéuticamente aceptable del mismo.
ARP150100403A 2012-02-07 2015-02-11 Prolinas / piperidinas sustituidas como antagonistas del receptor de orexina AR099466A1 (es)

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US201261596062P 2012-02-07 2012-02-07
US14/179,432 US9499517B2 (en) 2012-02-07 2014-02-12 Substituted prolines / piperidines as orexin receptor antagonists

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AR099466A1 true AR099466A1 (es) 2016-07-27

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EP (1) EP2811997B1 (es)
JP (1) JP6346862B2 (es)
KR (1) KR20140124398A (es)
CN (1) CN104220065A (es)
AR (1) AR099466A1 (es)
AU (1) AU2013217323A1 (es)
BR (1) BR112014019426A8 (es)
CA (1) CA2863413A1 (es)
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BR112014019426A8 (pt) 2017-07-11
HK1204955A1 (zh) 2015-12-11
US9896452B2 (en) 2018-02-20
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US20140364432A1 (en) 2014-12-11
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