公开(公告)号：ECSP13012838A

公开(公告)日：2013-09-30

申请号：ECSP13012838

申请日：2013-08-16

Applicant: HOFFMANN LA ROCHE

Inventor： WICHMANN JURGEN ,  RODRIGUEZ SARMIENTO ROSA MARIA

IPC: C07D317/66 ,  A61K31/36 ,  A61P25/18 ,  C07D405/12 ,  C07D407/12 ,  C07D413/12

Abstract: La presente invención se refiere a nuevos moduladores duales de los receptores de la 5-HT2A y de la D3, de la fórmula (I) (I)en la que n, Y, R1, R2, R3 y R4 tienen los significados aquí definidos, así como las sales y ésteres farmacéuticamente aceptables de los mismos. La presente invención se refiere además a la obtención de los compuestos de la fórmula (I), a composiciones farmacéuticas que los contienen y a su utilización como medicamentos.

公开(公告)号：MX2012000814A

公开(公告)日：2012-03-14

申请号：MX2012000814

申请日：2010-07-14

Applicant: HOFFMANN LA ROCHE

Inventor： WICHMANN JURGEN ,  JAESCHKE GEORG ,  VIEIRA ERIC ,  LINDEMANN LOTHAR

IPC: C07D401/04 ,  A61K31/4439 ,  A61P25/00 ,  C07D401/14 ,  C07D403/04

Abstract: La presente invención, se refiere a derivados de imidazol de la fórmula general (ver fórmula (I)) en donde R1, significa halógeno, alquilo inferior á alcoxi inferior; R2, significa alquilo inferior, hidroxialquilo inferior, o alcoxialquilo inferior; R3, significa hidrógeno, alquilo inferior, hidroxialquilo inferior o alcoxialquilo; Q, significa ó -N= ó -CH=; R4, es un grupo de la formula IIa ó IIb (ver fórmula (IIa y IIb)) en donde, X, Y y Z, son, de una forma independiente, -CH= ó -N=; y en donde, solamente una de entre las X ó Y, puede ser un átomo de nitrógeno; R5 y R6 son, de una forma independiente, hidrógeno, alquilo inferior, hidroxialquilo inferior, alcoxialquilo inferior, -(CH2)m-(CO)O-alquilo inferior, -(CH2)m-S(O)2-alquilo inferior, (CH2)m-C(O)-NR'R'', y en donde, m = 0 - 3 y R' y R' son, de una forma independiente, hidrógeno ó alquilo inferior, así como a las sales farmacéuticamente aceptables de éstos. Se ha encontrado ahora, de una forma sorprendente, el hecho de que, los compuestos de la fórmula general I, son antagonistas de los receptores metabotrópicos de glutamato. Éstos pueden utilizarse en el tratamiento o la prevención de trastornos mediatizados por el receptor mGluR5.

公开(公告)号：CA2274201C

公开(公告)日：2010-02-09

申请号：CA2274201

申请日：1999-06-09

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  CESURA ANDREA ,  JENCK FRANCOIS ,  KOLCZEWSKI SABINE ,  ROVER STEPHAN ,  WICHMANN JURGEN

IPC: C07D401/04 ,  C07D471/10 ,  A61K20060101 ,  A61K31/00 ,  A61K31/395 ,  A61K31/40 ,  A61K31/435 ,  A61K31/438 ,  A61K31/44 ,  A61K31/445 ,  A61P3/04 ,  A61P3/12 ,  A61P9/00 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/08 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P25/36 ,  A61P43/00 ,  C07D20060101 ,  C07D207/00 ,  C07D209/00 ,  C07D211/00 ,  C07D221/00 ,  C07D271/00 ,  C07D277/00 ,  C07D401/00 ,  C07D401/14 ,  C07D405/04 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  C07D471/20 ,  C07D487/12 ,  C07D498/10 ,  C07D513/10

Abstract: The present invention relates to compounds of the general formula (see formula I) wherein R1 is C6-10-cycloalkyl, optionally substituted by lower alkyl or -C(O)O-lower alkyl; decahydro-naphthalen-1-yl; decahydro-naphthalen-2-yl; indan-1-yl or indan-2-yl, optionally substituted by lower alkyl; decahydro-azulen-2-yl; bicyclo[6.2.0]dec-9-yl; acenaphthen-1-yl; 2,3-dihydro-1H-phenalen-1-yl; 2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl or octahydro-inden-2-yl; R2 is hydrogen; lower alkyl; =O or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; ~ is cyclohexyl or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; X is -CH(OH)-; -C(O)-; -CHR3-; -CR3=; -O-; -S-; -CH(COOR4)- or -C(COOR4)=; Y is -CH2-; -CH=; -CH(COOR4)-, -C(COOR4)=; or -C(CN)-; R3 is hydrogen or lower alkoxy; R4 is lower alkyl, cycloalkyl, phenyl, or benzyl and either a or b is optionally an additional bond, and to pharmaceutically acceptable acid addition salts thereof. The compounds are agonists and/or antagonists of the orphanin FQ (QFQ) receptor and therefore useful in the treatment of diseases, related to this receptor.

公开(公告)号：MA26779A1

公开(公告)日：2004-12-20

申请号：MA26339

申请日：2001-09-25

Applicant: HOFFMANN LA ROCHE

Inventor： VIEIRA ERIC ,  WICHMANN JURGEN ,  MUTEL VINCENT

IPC: A61K31/40 ,  A61K31/4025 ,  A61K31/4439 ,  A61P3/08 ,  A61P9/10 ,  A61P25/00 ,  A61P25/06 ,  A61P25/14 ,  A61P25/18 ,  A61P25/24 ,  A61P25/28 ,  A61P25/34 ,  A61P25/36 ,  C07D207/06 ,  C07D207/08 ,  C07D207/09 ,  C07D207/48 ,  C07D401/04 ,  C07D405/04 ,  C07D409/04 ,  C07D417/04

公开(公告)号：PT963985E

公开(公告)日：2003-06-30

申请号：PT99110954

申请日：1999-06-07

Applicant: HOFFMANN LA ROCHE

Inventor： KOLCZEWSKI SABINE ,  ADAM GEO ,  JENCK FRANCOIS ,  ROEVER STEPHAN ,  WICHMANN JURGEN ,  CESURA ANDREA

IPC: A61K20060101 ,  A61K31/00 ,  A61K31/395 ,  A61K31/40 ,  A61K31/435 ,  A61K31/438 ,  A61K31/44 ,  A61K31/445 ,  A61P3/04 ,  A61P3/12 ,  A61P9/00 ,  A61P25/00 ,  A61P25/02 ,  C07D401/04 ,  A61P25/04 ,  A61P25/08 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P25/36 ,  A61P43/00 ,  C07D20060101 ,  C07D207/00 ,  C07D209/00 ,  C07D211/00 ,  C07D221/00 ,  C07D271/00 ,  C07D277/00 ,  C07D401/00 ,  C07D401/14 ,  C07D405/04 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  C07D471/10 ,  C07D471/20 ,  C07D487/12 ,  C07D498/10 ,  C07D513/10

Abstract: The present invention relates to compounds of the general formula wherein R is C6-10-cycloalkyl, optionally substituted by lower alkyl or -C(O)O-lower alkyl; decahydro-naphthalen-1-yl; decahydro-naphthalen-2-yl; indan-1-yl or indan-2-yl, optionally substituted by lower alkyl; decahydro-azulen-2-yl; bicycloÄ6.2.0Üdec-9-yl; acenaphthen-1-yl; 2,3-dihydro-1H-phenalen-1-yl; 2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl or octahydro-inden-2-yl; R is hydrogen; lower alkyl; =O or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; A &cir& is cyclohexyl or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; X is -CH(OH)-; -C(O)-; -CHR -; -CR =; -O-; -S-; -CH(COOR )- or - C(COOR )=; Y is -CH2-; -CH=; -CH(COOR )-, -C(COOR )=; or -C(CN)-; R is hydrogen or lower alkoxy; R is lower alkyl, cycloalkyl, phenyl, or benzyl and either a or b is optionally an additional bond, and to pharmaceutically acceptable acid addition salts thereof. The compounds are agonists and/or antagonists of the orphanin FQ (QFQ) receptor and therefore useful in the treatment of diseases, related to this receptor.

公开(公告)号：AR028817A1

公开(公告)日：2003-05-28

申请号：ARP000101297

申请日：2000-03-23

Applicant: HOFFMANN LA ROCHE

Inventor： MUTEL VINCENT ,  VIEIRA ERIC ,  WICHMANN JURGEN

IPC: A61K31/40 ,  A61K31/4025 ,  A61K31/4439 ,  A61P3/08 ,  A61P9/10 ,  A61P25/00 ,  A61P25/06 ,  A61P25/14 ,  A61P25/18 ,  A61P25/24 ,  A61P25/28 ,  A61P25/34 ,  A61P25/36 ,  C07D207/06 ,  C07D207/08 ,  C07D207/09 ,  C07D207/48 ,  C07D401/04 ,  C07D405/04 ,  C07D409/04 ,  C07D417/04

Abstract: Compuestos derivados de la 1 -arenosulfonil- 2 - arilo- pirrolidina de formula general 1 en donde R1 significa, hidrogeno, alquilo inferior o hidroxilo --alquilo inferior; R2 significa furilo, tienilo, piridilo o fenilo, el cual está opcionalmente sustituido por 1 a 3 sustituyentes seleccionado de alquilo inferior, alcoxilo inferior, halogeno, ciano, CF3 o -N (R4)2; R3 significa naftilo o fenilo, el cual está opcionalmente sustituido con 1 a 3 sustituyentes de alquilo inferior, alcoxilo inferior, halogeno, acetilo, ciano, hidroxilo - -alquilo inferior, -CH2 - morfolin- 4- ilo, alquilo inferior- oxi- alquilo inferior, alquilo inferior - N(R4)2 o CF3; R4 significa, independientemente entre sí, hidrogeno o alquilo inferior, con la excepcion de la (RS) - 2 - fenil - 1 - (toluen - 4 -sulfonil)- pirrolidina y (RS) - 1- (toluen- 4 - sulfonil)- 2 - ptolil- pirrolidina así como sus sales farmacéuticamente aceptables. Los compuestos descritos más arriba son antagonistas o agonistas del receptor metabotropico de glutamato, y por lo tanto son de utilidad en el tratamiento de los correspondientes trastornos del SNC.

公开(公告)号：ES2181336T3

公开(公告)日：2003-02-16

申请号：ES99110944

申请日：1999-06-07

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  DAUTZENBERG FRANK ,  KOLCZEWSKI SABINE ,  ROEVER STEPHAN ,  WICHMANN JURGEN

IPC: C07D401/14 ,  A01N43/42 ,  A61K31/00 ,  A61K31/395 ,  A61K31/435 ,  A61K31/438 ,  A61K31/44 ,  A61K31/445 ,  A61K31/505 ,  A61K31/535 ,  A61P3/04 ,  A61P3/12 ,  A61P9/12 ,  A61P25/04 ,  A61P25/08 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P43/00 ,  C07D20060101 ,  C07D209/00 ,  C07D221/00 ,  C07D471/10 ,  C07D471/20 ,  C07D487/20 ,  C07D498/10 ,  C07D513/10

Abstract: The present invention relates to compounds of the general formula wherein the substituents are described in the application and to pharmaceutically acceptable acid addition salts thereof. The compound of the invention are useful in the treatment of diseases related to the orphanin FQ (OFQ) receptor, which include psychiatric, neurological and physiological disorders, such as anxiety and stress disorders, depression, trauma, memory loss due to Alzheimer's disease or other dementias, deficits in cognition and leaning, epilepsy and convulsions, acute and/or chronic pain conditions, and symptoms of addictive drug withdrawal, control of water balance, Na excretion, arterial blood pressure disorders and metabolic disorders such as obesity.

公开(公告)号：PT963987E

公开(公告)日：2003-01-31

申请号：PT99110944

申请日：1999-06-07

Applicant: HOFFMANN LA ROCHE

Inventor： KOLCZEWSKI SABINE ,  ADAM GEO ,  ROEVER STEPHAN ,  WICHMANN JURGEN ,  DAUTZENBERG FRANK

IPC: C07D401/14 ,  A01N43/42 ,  A61K31/00 ,  A61K31/395 ,  A61K31/435 ,  A61K31/438 ,  A61K31/44 ,  A61K31/445 ,  A61K31/505 ,  A61K31/535 ,  A61P3/04 ,  A61P3/12 ,  A61P9/12 ,  A61P25/04 ,  A61P25/08 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P43/00 ,  C07D20060101 ,  C07D209/00 ,  C07D221/00 ,  C07D471/10 ,  C07D471/20 ,  C07D487/20 ,  C07D498/10 ,  C07D513/10

Abstract: The present invention relates to compounds of the general formula wherein the substituents are described in the application and to pharmaceutically acceptable acid addition salts thereof. The compound of the invention are useful in the treatment of diseases related to the orphanin FQ (OFQ) receptor, which include psychiatric, neurological and physiological disorders, such as anxiety and stress disorders, depression, trauma, memory loss due to Alzheimer's disease or other dementias, deficits in cognition and leaning, epilepsy and convulsions, acute and/or chronic pain conditions, and symptoms of addictive drug withdrawal, control of water balance, Na excretion, arterial blood pressure disorders and metabolic disorders such as obesity.

公开(公告)号：PT700905E

公开(公告)日：2002-04-29

申请号：PT95112270

申请日：1995-08-04

Applicant: HOFFMANN LA ROCHE

Inventor： WICHMANN JURGEN

IPC: A61K31/415 ,  A61K31/416 ,  A61P1/00 ,  A61P3/04 ,  A61P9/00 ,  A61P15/08 ,  A61P25/00 ,  A61P25/04 ,  A61P25/18 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  A61P25/30 ,  C07D231/54 ,  C07D231/56

Abstract: Issued in Week 9616. First Major Country Equivalent to NO9503162A. minoalkyl-substd. tricyclic pyrazoles of formula (I) and their salts are new: R -R = H, OH, halo, lower alkyl, or lower alkoxy; R = H or lower alkyl; R = H, lower alkyl or lower alkoxy; X = (CR R )n or CH=CH; R , R = H or lower alkyl; n = 1 or 2.

公开(公告)号：PT970957E

公开(公告)日：2002-02-28

申请号：PT99110943

申请日：1999-06-07

Applicant: HOFFMANN LA ROCHE

Inventor： KOLCZEWSKI SABINE ,  WICHMANN JURGEN ,  CESURA ANDREA ,  JENCK FRANCOIS ,  ADAM GEO ,  ROEVER STEPHAN

IPC: C07D401/00 ,  A61K31/00 ,  A61K31/438 ,  A61P3/04 ,  A61P9/10 ,  A61P25/04 ,  A61P25/08 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  C07D471/10 ,  A61K31/445

Abstract: The invention relates to compounds of the general formula wherein R is C6-12-cycloalkyl, optionally substituted by lower alkyl or C(O)O lower alkyl, indan-1-yl or indan-2-yl, optionally substituted by lower alkyl; acenaphthen-1-yl; bicycloÄ3.3.1Ünon-9-yl, octahydro-inden-2-yl; 2,3-dihydro-1H-phenalen-1-yl; 2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl, decahydro-azulen-2-yl; bicycloÄ6.2.0Üdec-9-yl; decahydro-naphthalen-1-yl, decahydro-naphthalen-2-yl; tetrahydro-naphthalen-1-yl, tetrahydro-naphthalen-2-yl or 2-oxo-1,2-diphenyl-ethyl; R is =O or hydrogen, R is hydrogen, isoindolyl-1,3-dione, lower alkoxy, lower alkyl, amino, benzyloxy, -CH2OR or -CH2N(R )2; R is hydrogen or -CH2OR ; R is hydrogen or lower alkyl; A &cir& is cyclohexyl or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; to racemic mixtures and their corresponding enantiomers and or pharmaceutically acceptable acid addition salts thereof. The compounds of the present invention are agonists and/or antagonists of the orphamin FQ (OFQ) receptor and therefore useful in the treatment of diseases, related to this receptor.