AR069207A1 - Ureas ciclicas como inhibidores de la 11 beta - hidroxi-esteroide deshidrogenasa 1 - Google Patents
Ureas ciclicas como inhibidores de la 11 beta - hidroxi-esteroide deshidrogenasa 1Info
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- AR069207A1 AR069207A1 ARP080104852A ARP080104852A AR069207A1 AR 069207 A1 AR069207 A1 AR 069207A1 AR P080104852 A ARP080104852 A AR P080104852A AR P080104852 A ARP080104852 A AR P080104852A AR 069207 A1 AR069207 A1 AR 069207A1
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- alkyl
- alkoxy
- cycloalkyl
- 2nhc
- alkylamino
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Abstract
Se refiere a composiciones farmacéuticas de los mismos, que son utiles para el tratamiento terapéutico de enfermedades asociadas con la modulacion o inhibicion de 11beta-HSD1 en mamíferos, también se refiere a composiciones farmacéuticas de los nuevos compuestos y métodos para su uso en la reduccion o control de la produccion de cortisol en una célula o la inhibicion de la conversion de cortisona en cortisol en una célula. Reivindicacion 1: Un compuesto de formula (1) en la que: R1 está (a) ausente o (b) se selecciona entre alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alcoxi C1-3-alcoxi C1-3 o alcoxi C1-3-alquilo C1-3 y está opcionalmente sustituido con hasta cuatro grupos seleccionados independientemente entre fluor, ciano, oxo, R4, R4O-, (R4)2N-, R4O2C-, R4S, R4S(=O)-, R4S(=O)2-, R4C(=O)NR4-, (R4)2NC(=O)-, (R4)2NC(=O)O-, (R4)2NC(=O)NR4-, R4OC(=O)NR4-, (R4)2NC(=NCN)NR4-, (R4O)2P(=O)O-, (R4O)2P(=O)NR4-; R4OS(=O)2NR4-, (R4)2NS(=O)2O-, (R4)2NS(=O)2NR4-, R4S(=O)2NR4-, R4S(=O)2NHC(=O)-, R4S(=O)2NHC(=O)O-, R4S(=O)2NHC(=O)NR4-, R4OS(=O)2NHC(=O)-, R4OS(=O)2NHC(=O)O-, R4OS(=O)2NHC(=O)NR4, (R4)2NS(=O)2NHC(=O), (R4)2NS(=O)2NHC(=O)O-, (R4)2NS(=O)2NHC(=O)NR4-, R4C(=O)NHS(=O)2-, R4C(=O)NHS(=O)2O-, R4C(=O)NHS(=O)2NR4-, R4OC(=O)NHS(=O)2-, R4OC(=O)NHS(=O)2O-, R4OC(=O)NHS(=O)2NR4-, (R4)2NC(=O)NHS(=O)2-, (R4)2NC(=O)NHS(=O)2O-, (R4)2NC(=O)NHS(=O)2NR4-, arilo, cicloalquilo, heterociclilo, heteroarilo, arilamino y heteroarilamino; A1 es (a) un enlace) o (b) alquileno C1-3, CH2CH2O, donde el oxigeno está unido a Cy1, o CH2C(=O), donde el carbono del carbonilo está unido a Cy1; Cy1 es arilo, heteroarilo, cicloalquilo monociclico o heterociclilo monocíclico y está opcionalmente sustituido con 1 a 4 grupos seleccionados independientemente entre fluor, cloro, bromo, yodo, ciano, nitro, amino, hidroxi, carboxi, alquilo C1-6, hidroxialquilo C1-6, cicloalquilo C3-6, hidroxicicloalquilo C3-6, cicloalquilalquilo C4-7, alquenilo C2-6, haloalquenilo C2-6, hidroxialquenilo C2-6, alquinilo C2-6, cicloalquil C3-6-alquinilo C2-4, haloalquilo C1-6, halocicloalquilo C3-6, halocicloalquilalquilo C4-7, alcoxi C1-6, cicloalcoxi C3-6, cicloalquilalcoxi C4-7, haloalcoxi C1-6, halocicloalcoxi C3-6, halocicloalquilalcoxi C4-7, alquiltio C1-6, cicloalquiltio C3-6, cicloalquilalquiltio C4-7, haloalquiltio C1-6, halocicloalquiltio C3-6, halocicloalquilalquiltio C4-7, alcanosulfinilo C1-6, cicloalcanosulfinilo C3-6, cicloalquilalcanosulfinilo C4-7, haloalcanosulfinilo C1-6, halocicloalcanosulfinilo C3-6, halocicloalquilalcanosulfinilo C4-7, alcanosulfonilo C1-6, cicloalcanosulfonilo C3-6, cicloalquilalcanosulfonilo C4-7, haloalcanosulfonilo C1-6, halocicloalcanosulfonilo C3-6, halocicloalquilalcanosulfonilo C4-7, alquilamino C1-6, dialquilamino C1-6, alcoxi C1-6-alcoxi C1-6, haloalcoxi C1-6-alcoxi C1-6, alcoxicarbonilo C1-6, H2NCO, H2NSO2, alquilaminocarbonilo C1-6, dialquilaminocarbonilo C1-6, alcoxi C1-3-alquilaminocarbonilo C1-3, heterociclilcarbonilo, alquilaminosulfonilo C1-6, dialquilaminosulfonilo C1-6, heterociclosulfonilo, alquilcarbonilamino C1-6, alquilcarbonilamino C1-6-alquilo C1-6, alquilsulfonilamino C1-6, alquilsulfonilamino C1-6-alquilo C1-6, alcoxicarbonil C1-6-alcoxi C1-6, alcoxi C1-6-alquilo C1-6, haloalcoxi C1-6-alquilo C1-6, hidroxialcoxi C1-6, heteroarilo, oxo, aminoalquilo C1-6, alquilamino C1-6-alquilo C1-6, dialquilamino C1-6-alquilamino C1-6-alcoxi C2-6, alquilamino C1-6-alcoxi C2-6, dialquilamino C1-6-alcoxi C2-6, alquilcarbonilo C1-6, cicloalquilcarbonilo C3-6, cicloalquilaminocarbonilo C3-6, {cicloalquil C3-6}{alquil C1-6}aminocarbonilo, dicicloalquilaminocarbonilo C3-6, cicloalquilaminosulfonilo C3-6, {cicloalquil C3-6}{alquil C1-6}aminosulfonilo, dicicloalquilaminosulfonilo C3-6, cianoalquilo C1-6, aminocarbonilalquilo C1-6, alquilaminocarbonil C1-6-alquilo C1-6, dialquilaminocarbonil C1-6-alquilo C1-6, cicloalquilaminocarbonil C3-6-alquilo C1-6, {cicloalquil C3-6}{alquil C1-6}aminocarbonilalquilo C1-6 y dicicloalquilaminocarbonil C3-6-alquilo C1-6; A2 es (a) un enlace, O, S o NR4; o (b) alquileno C1-3 o alquilenooxi C1-2, cada uno de los cuales está opcionalmente sustituido con 1 a 4 grupos seleccionados independientemente entre metilo, etilo, trifluorometilo u oxo; Cy2 es (a) hidrogeno o (b) arilo, heteroarilo, cicloalquilo o heterociclilo y está opcionalmente sustituido, con 1 a 4 grupos seleccionados independientemente entre fluor, cloro, bromo, yodo, ciano, nitro, amino, hidroxi, carboxi, alquilo C1-6, hidroxialquilo C1-6, cicloalquilo C3-6, hidroxicicloalquilo C3-6, cicloalquilalquilo C4-7, alquenilo C2-6, haloalquenilo C2-6, hidroxialquenilo C2-6, alquinilo C2-6, cicloalquil C3-6-alquinilo C2-4, haloalquilo C1-6, halocicloalquilo C3-6, halocicloalquilalquilo C4-7, alcoxi C1-6, cicloalcoxi C3-6, cicloalquilalcoxi C4-7, haloalcoxi C1-6, halocicloalcoxi C3-6, halocicloalquilalcoxi C4-7, alquiltio C1-6, cicloalquiltio C3-6, cicloalquilalquiltio C4-7, haloalquiltio C1-6, halocicloalquiltio C3-6, halocicloalquilalquiltio C4-7, alcanosulfinilo C1-6, cicloalcanosulfinilo C3-6, cicloalquilalcanosulfinilo C4-7, haloalcanosulfinilo C1-6, halocicloalcanosulfinilo C3-6, halocicloalquilalcanosulfinilo C4-7, alcanosulfonilo C1-6, cicloalcanosulfonilo C3-6, cicloalquilalcanosulfonilo C4-7, haloalcanosulfonilo C3-6, halocicloalcanosulfonilo C3-6, halocicloalquilalcanosulfonilo C4-7, alquilamino C1-6, dialquilamino C1-6, alcoxi C1-6-alcoxi C1-6, haloalcoxi C1-6-alcoxi C1-6, alcoxicarbonilo C1-6, H2NCO, H2NSO2, alquilaminocarbonilo C1-6, dialquilaminocarbonilo C1-6, alcoxi C1-3-alquilaminocarbonilo C1-3, heterociclilcarbonilo, alquilaminosulfonilo C1-6, dialquilaminosulfonilo C1-6, heterociclosulfonilo, alquilcarbonilamino C1-6, alquilcarbonil C1-6-aminoalquilo C1-6, alquilsulfonilamino C1-6, alquilsulfonilamino C1-6-alquilo C1-6, alcoxicarbonil C1-6-alcoxi C1-6, alcoxi C1-6-alquilo C1-6, haloalcoxi C1-6-alquilo C1-6, hidroxialcoxi C1-6, heteroarilo, oxo, aminoalquilo C1-6, alquilamino C1-6-alquilo C1-6, dialquilamino C1-6-alquilamino C1-6-alcoxi C2-6, alquilamino C1-6-alcoxi C2-6, dialquilamino C1-6-alcoxi C2-6, alquilcarbonilo C1-6, cicloalquilcarbonilo C3-6, cicloalquilaminocarbonilo C3-6, {cicloalquil C3-6}{alquil C1-6}aminocarbonilo, dicicloalquilaminocarbonilo C3-6, cicloalquilaminosulfonilo C3-6, {cicloalquil C3-6}{alquil C1-6}aminosulfonilo, dicicloalquilaminosulfonilo C3-6, cianoalquilo C1-6, aminocarbonilalquilo C1-6, alquilaminocarbonil C1-6-alquilo C1-6, dialquilaminocarbonil C1-6-alquilo C1-6, cicloalquilaminocarbonil C3-6-alquilo C1-6, {cicloalquil C3-6}{alquil C1-6}aminocarbonilalquilo C1-6 y dicicloalquilaminocarbonil C3-6-alquilo C1-6; n es 0, 1 o 2; E es (a) un enlace o (b) alquileno C1-3 o alquileniloxi C1-2, donde el O está unido a R2, cada uno de los cuales está opcionalmente sustituido con 1 a 4 grupos seleccionados independientemente entre metilo, etilo, trifluorometilo u oxo; R2 es alquilo C1-6, arilo, heteroarilo, cicloalquilo o heterociclilo, donde cada uno está opcionalmente sustituido con hasta 4 grupos seleccionados independientemente entre fluor, cloro, bromo, yodo, ciano, nitro, amino, hidroxi, carboxi, alquilo C1-6, hidroxialquilo C1-6, cicloalquilo C3-6, hidroxicicloalquilo C3-6, cicloalquilalquilo C4-7, alquenilo C2-6, haloalquenilo C2-6, hidroxialquenilo C2-6, alquinilo C2-6, cicloalquil C3-6-alquinilo C2-4, haloalquilo C1-6, halocicloalquilo C3-6, halocicloalquilalquilo C4-7, alcoxi C1-6, cicloalcoxi C3-6, cicloalquilalcoxi C4-7, haloalcoxi C1-6, halocicloalcoxi C3-6, halocicloalquilalcoxi C4-7, alquiltio C1-6, cicloalquiltio C3-6, cicloalquilalquiltio C4-7, haloalquiltio C1-6, halocicloalquiltio C3-6, halocicloalquilalquiltio C4-7, alcanosulfinilo C1-6, cicloalcanosulfinilo C3-6, cicloalquilalcanosulfinilo C4-7, haloalcanosulfinilo C1-6, halocicloalcanosulfinilo C3-6, halocicloalquilalcanosulfinilo C4-7, alcanosulfonilo C1-6, cicloalcanosulfonilo C3-6, cicloalquilalcanosulfonilo C4-7, haloalcanosulfonilo C1-6, halocicloalcanosulfonilo C3-6, halocicloalquilalcanosulfonilo C4-7, alquilamino C1-6, dialquilamino C1-6, alcoxi C1-6-alcoxi C1-6, haloalcoxi C1-6-alcoxi C1-6, alcoxicarbonilo C1-6, H2NCO, H2NSO2, alquilaminocarbonilo C1-6, dialquilaminocarbonilo C1-6, alcoxi C1-3-alquila C1-3-aminocarbonilo, heterociclilcarbonilo, alquilaminosulfonilo C1-6, dialquilaminosulfonilo C1-6, heterociclosulfonilo, alquilcarbonilamino C1-6, alquilcarbonil C1-6-aminoalquilo C1-6, alquilsulfonilamino C1-6, alquilsulfonilamino C1-6-alquilo C1-6, alcoxicarbonil C1-6-alcoxi C1-6, alcoxi C1-6-alquilo C1-6, haloalcoxi C1-6-alquilo C1-6, hidroxialcoxi C1-6, heteroarilo, oxo, aminoalquilo C1-6, alquilamino C1-6-alquilo C1-6, dialquilamino C1-6-alquilamino C1-6-alcoxi C2-6, alquilamino C1-6-alcoxi C2-6, dialquilamino C1-6-alcoxi C2-6, alquilcarbonilo C1-6, cicloalquilcarbonilo C3-6, cicloalquilaminocarbonilo C3-6, {cicloalquil C3-6}{alquil C1-6}aminocarbonilo, dicicloalquilaminocarbonilo C3-6, cicloalquilaminosulfonilo C3-6, {cicloalquil C3-6}{alquil C1-6}aminosulfonilo, dicicloalquilaminosulfonilo C3-6, cianoalquilo C1-6, aminocarbonilalquilo C1-6, alquilaminocarbonil C1-6-alquilo C1-6, dialquilaminocarbonil C1-6-alquilo C1-6, cicloalquilaminocarbonil C3-6-alquilo C1-6, {cicloalquil C3-6}{alquil C1-6}aminocarbonilalquilo C1-6 y dicicloalquilaminocarbonil C3-6-alquilo C1-6; R3 se selecciona entre alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquil C3-5-alquilo C1-4, alcoxi C1-3-alcoxi C1-3 o alcoxi C1-3-alquilo C1-3 y está opcionalmente sustituido con hasta cuatro grupos seleccionados independientemente entre fluor, ciano, oxo, R4, R4O-, (R4)2N-, R4O2C-, R4S, R4S(=O)-, R4S(=O)2-, R4C(=O)NR4-, (R4)2NC(=O)-, (R4)2NC(=O)O-, (R4)2NC(=O)NR4-, R4OC(=O)NR4-, (R4)2NC(=NCN)NR4-, (R4O)2P(=O)O-, (R4O)2P(=O)NR4-; R4OS(=O)2NR4-, (R4)2NS(=O)2O-, (R4)2NS(=O)2NR4-, R4S(=O)2NR4-, R4S(=O)2NHC(=O)-, R4S(=O)2NHC(=O)O-, R4S(=O)2NHC(=O)NR4-, R4OS(=O)2NHC(=O)-, R4OS(=O)2NHC(=O)O-, R4OS(=O)2NHC(=O)NR4, (R4)2NS(=O)2NHC(=O)-, (R4)2NS(=O)2NHC(=O)O-,
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AR078887A1 (es) | 2009-11-06 | 2011-12-07 | Boehringer Ingelheim Int | Derivados arilo y heteroarilcarbonilo de hexahidroindenopiridina y octahidrobenzoquinolina y composiciones farmaceuticas que los contienen. |
EP2582698B1 (en) | 2010-06-16 | 2016-09-14 | Vitae Pharmaceuticals, Inc. | Substituted 5-,6- and 7-membered heterocycles, medicaments containing such compounds, and their use |
EP2585444B1 (en) | 2010-06-25 | 2014-10-22 | Boehringer Ingelheim International GmbH | Azaspirohexanones as inhibitors of 11-beta-hsd1 for the treatment of metabolic disorders |
EA201300522A1 (ru) | 2010-11-02 | 2013-11-29 | Бёрингер Ингельхайм Интернациональ Гмбх | Фармацевтические комбинации для лечения метаболических нарушений |
-
2008
- 2008-11-06 AR ARP080104852A patent/AR069207A1/es unknown
- 2008-11-07 WO PCT/US2008/012618 patent/WO2009061498A1/en active Application Filing
- 2008-11-07 JP JP2010533113A patent/JP5695906B2/ja not_active Expired - Fee Related
- 2008-11-07 TW TW097143034A patent/TW200934495A/zh unknown
- 2008-11-07 EP EP08846298.1A patent/EP2220052B1/en not_active Not-in-force
- 2008-11-07 CL CL2008003339A patent/CL2008003339A1/es unknown
- 2008-11-07 US US12/745,663 patent/US9079861B2/en not_active Expired - Fee Related
- 2008-11-07 CA CA2704222A patent/CA2704222A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
JP5695906B2 (ja) | 2015-04-08 |
US20100324045A1 (en) | 2010-12-23 |
US9079861B2 (en) | 2015-07-14 |
JP2011503068A (ja) | 2011-01-27 |
CL2008003339A1 (es) | 2009-10-16 |
EP2220052B1 (en) | 2015-03-25 |
EP2220052A1 (en) | 2010-08-25 |
CA2704222A1 (en) | 2009-05-14 |
WO2009061498A1 (en) | 2009-05-14 |
TW200934495A (en) | 2009-08-16 |
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