公开(公告)号：JP2000053680A

公开(公告)日：2000-02-22

申请号：JP16397599

申请日：1999-06-10

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  DAUTZENBERG FRANK ,  KOLCZEWSKI SABINE ,  ROVER STEPHAN ,  WICHMANN JUERGEN

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: PROBLEM TO BE SOLVED: To obtain a new compound useful for treating diseases related to orphanin FQ receptor including anxiety, stress disorder, depression, trauma, etc. SOLUTION: This compound is shown by formula I (R1 is a 5-12C cycloalkyl substitutable with a lower alkyl or the like; R2 and R3 are each H, OH or the like; R4 is H or the like; R5 is H or the like), preferably (3'aS,6'aR)-5'- ethyl-2'-phenyl-1-[(R)-1,2,3,4-tetrahydro-naphthalen-1-yl]-hexahydro- spiro[piperidine-4,1'-pyrrolo[3,4-c]pyrrole], etc. The compound of formula I obtained, as one favorable production process, by reducing a compound of formula II e.g. (3'aR,6'aS)-5'-ethyl-1-[(R)-1,2,3,4-tetrahydro-naphthalen-1-yl]-2'- phenyl-hexahydro-spiro[piperidine-4,1'-pyrrolo[3,4-c]pyrrole]-4',6'-dione or the like).

公开(公告)号：WO0220488A3

公开(公告)日：2002-05-16

申请号：PCT/EP0110014

申请日：2001-08-30

Applicant: HOFFMANN LA ROCHE

Inventor： BREU VOLKER ,  DAUTZENBERG FRANK ,  GUERRY PHILIPPE ,  NETTEKOVEN MATTHIAS HEINRICH ,  PFLIEGER PHILIPPE

IPC: C07D239/94 ,  A61K31/365 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/506 ,  A61K31/517 ,  A61K31/5377 ,  A61K31/55 ,  A61K45/00 ,  A61P1/14 ,  A61P3/00 ,  A61P3/04 ,  A61P3/10 ,  A61P9/00 ,  A61P13/12 ,  A61P19/02 ,  A61P43/00 ,  C07D215/00 ,  C07D215/42 ,  C07D239/84 ,  C07D401/04 ,  C07D409/04 ,  A61K31/4706

CPC classification number: C07D401/04 ,  C07D215/42 ,  C07D239/84 ,  C07D409/04

Abstract: Compounds of formula (I) as well as pharmaceutically usable salts, solvates and esters thereof, wherein R , R , R , R , A and A have the significance given in claim 1, can be used in the form of pharmaceutical preparations for the treatment or prevention of arthritis, cardiovascular diseases, diabetes, renal failure, eating disorders and obesity.

Abstract translation: 式（I）化合物及其可药用的盐，溶剂合物和酯，其中R 1，R 2，R 3，R 4，A 1和A 2具有 权利要求1中给出的意义可以以用于治疗或预防关节炎，心血管疾病，糖尿病，肾衰竭，进食障碍和肥胖的药物制剂的形式使用。

公开(公告)号：DE60123458D1

公开(公告)日：2006-11-09

申请号：DE60123458

申请日：2001-11-06

Applicant: HOFFMANN LA ROCHE

Inventor： BREU VOLKER ,  DAUTZENBERG FRANK ,  MATTEI PATRIZIO ,  NEIDHART WERNER ,  PFLIEGER PHILIPPE

IPC: C07D239/42 ,  A61K31/337 ,  A61K31/505 ,  A61K31/506 ,  A61P3/04 ,  A61P3/10 ,  A61P19/02 ,  A61P43/00 ,  C07D401/04 ,  C07D401/06 ,  C07D403/04 ,  C07D403/06 ,  C07D405/06 ,  C07D409/06

Abstract: Pyrimidine derivatives have been found to be useful as neuropeptide Y receptor ligands and particularly as antagonists. These pyrimidine derivatives may be used in the form of pharmaceutical preparations for the treatment or prevention of arthritis, diabetes, eating disorders, and obesity.

公开(公告)号：AU2002227905B2

公开(公告)日：2006-10-05

申请号：AU2002227905

申请日：2001-11-06

Applicant: HOFFMANN LA ROCHE

Inventor： DAUTZENBERG FRANK ,  PFLIEGER PHILIPPE ,  MATTEI PATRIZIO ,  NEIDHART WERNER ,  BREU VOLKER

IPC: C07D239/42 ,  A61K31/337 ,  A61K31/505 ,  A61K31/506 ,  A61P3/04 ,  A61P3/10 ,  A61P19/02 ,  A61P43/00 ,  C07D401/04 ,  C07D401/06 ,  C07D403/04 ,  C07D403/06 ,  C07D405/06 ,  C07D409/06

Abstract: Pyrimidine derivatives have been found to be useful as neuropeptide Y receptor ligands and particularly as antagonists. These pyrimidine derivatives may be used in the form of pharmaceutical preparations for the treatment or prevention of arthritis, diabetes, eating disorders, and obesity.

公开(公告)号：NZ336186A

公开(公告)日：2000-10-27

申请号：NZ33618699

申请日：1999-06-09

Applicant: HOFFMANN-LA ROCHE

Inventor： ADAM GEO ,  DAUTZENBERG FRANK ,  KOLCZEWSKI SABINE ,  ROVER 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 application relates to compounds of the general formula wherein R1 is C5-12 -cycloalkyl, optionally substituted by 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; bicyclo[3.3.1]non-9-yl; 2,3-dihydro-1H-phenalen-1-yl; 2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl; octahydro-inden-2-yl; 1,2,3,4-tetrahydro-naphthalen-1-yl; 1,2,3,4-tetrahydro-naphthalen-2-yl; naphthalen-lower alkyl-1-yl; naphthalen-lower alkyl-2-yl; acenaphthen-1-yl; and 5-isopropyl-2-methyl-bicyclo[3.1.0]hex-3-yl; R2, R3 are hydrogen; hydroxy; lower alkyl; =O; or phenyl, optionally substituted by lower allyl, halogen or alkoxy; R4 is hydrogen; lower alkyl; --(CH2)n CH(OH)CF3 ; --(CH2)n C3-6 -cycloalkyl; phenyl; benzyl; tetrahydrofuran-3-yl; --(CH2)n OCH2 C6 H5 ; --(CH2)n morpholinyl; 3-methyl-oxetan-3-yl-methyl; --(CH2)n CH2 OH; --S(O)2 -lower alkyl; --C(O)-lower alkyl; --C(O)CF3 ; --C(O)(CH2)n OCH3 ; --(CH2)n C(O)N(lower alkyl)2 ; --S(O)2 heteroaryl; --C(O)heteroaryl; --S(O)2 -phenyl; --S(O)2 --N(lower alkyl)2 ; --C(O)--C3-6 -cycloalkyl; --C(O)O-phenyl; or --C(O)O-lower alkyl: R5 is hydrogen; halogen; lower alkyl; trifluoromethyl or lower alkoxy; n is 0-3; and to pharmaceutically acceptable acid addition salts thereof. The compounds of formula I and their salts are useful as in the treatment of psychiatric, neurological and physiological disorders.

公开(公告)号：ID23283A

公开(公告)日：2000-04-05

申请号：ID990577

申请日：1999-06-14

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  DAUTZENBERG FRANK ,  KOLCZEWSKI SABINE ,  ROVER 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：TR9901304A2

公开(公告)日：2000-01-21

申请号：TR9901304

申请日：1999-06-10

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  DAUTZENBERG FRANK ,  KOLCZEWSKI SABINE ,  ROVER 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 ,  C07D

CPC classification number: C07D471/20

公开(公告)号：TR199901304A2

公开(公告)日：2000-01-21

申请号：TR9901304

申请日：1999-06-10

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  DAUTZENBERG FRANK ,  KOLCZEWSKI SABINE ,  ROVER 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 ,  C07D

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：CA2274204C

公开(公告)日：2009-09-15

申请号：CA2274204

申请日：1999-06-09

Applicant: HOFFMANN LA ROCHE

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

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

Abstract: The present invention relates to compounds of the general formula (see formula I) 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 learning, epilepsy and convulsions, acu te and/or chronic pain conditions, and symptoms of addictive drug withdrawal, control of water balance, Na+ excretion, arterial blood pressure disorders a nd metabolic disorders such as obesity.

公开(公告)号：ES2271100T3

公开(公告)日：2007-04-16

申请号：ES01989438

申请日：2001-11-06

Applicant: HOFFMANN LA ROCHE

Inventor： BREU VOLKER ,  DAUTZENBERG FRANK ,  MATTEI PATRIZIO ,  NEIDHART WERNER ,  PFLIEGER PHILIPPE

IPC: C07D239/42 ,  A61K31/337 ,  A61K31/505 ,  A61K31/506 ,  A61P3/04 ,  A61P3/10 ,  A61P19/02 ,  A61P43/00 ,  C07D401/04 ,  C07D401/06 ,  C07D403/04 ,  C07D403/06 ,  C07D405/06 ,  C07D409/06

Abstract: Compuestos de formula I en donde R1 y R2 son cada uno independientemente alquilo, cicloalquilo o aralquilo o uno de Rl y R2 es hidrógeno y el otro es alquilo, aminoalquilo o ciclopropilo o Rl y R2 junto con el átomo de N al que están unidos forman un anillo heterocíclico de 4- a 10- miembros opcionalmente sustituido con de uno a tres sustituyentes independientemente seleccionados de alquilo, hidroxilo, alcoxilo, alcoxialquilo, hidroxialquilo o CONR5R6; R3 es alquilo, cicloalquilo, alcoxialquilo, hidroxialquilo, haloalquilo, alcoxilo, alcoxialcoxilo, hidroxi-alcoxialquilo, hidroxialcoxilo, aralquilo o amino; R4 es arilo o heteroarilo, en donde R4 no es nitro- furilo o nitro-tienilo; R5 y R6 son cada uno independientemente hidrógeno o alquilo; A1 es CH o N; A2 es CH o N; en donde uno de A1 y A2 es N y el otro es CH; y ésteres y sales utilizables farmacéuticamente de los mismos.