公开(公告)号：JPH1045624A

公开(公告)日：1998-02-17

申请号：JP13116097

申请日：1997-05-21

Applicant: HOECHST AG

Inventor： HEITSCH HOLGER ,  WAGNER ADALBERT ,  WIRTH KLAUS ,  HROPOT MAX ,  BICKEL MARTIN

IPC: A61K45/00 ,  A61K31/00 ,  A61K31/33 ,  A61K31/335 ,  A61K31/395 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/50 ,  A61K31/505 ,  A61K31/535 ,  A61K31/54 ,  A61P43/00

Abstract: PROBLEM TO BE SOLVED: To carry out the treatment of chronic fibroplastic hepatopathy (hepatic cirrhosis or hepatic fibrosis), etc., by using a specific non-peptide bradykinin antagonistic agent. SOLUTION: This non-peptide bradykinin antagonistic agent is preferably a compound of formula I D is a group of formula II [X is N or C-R ; X is N or C-R ; X is N or C-R (R is H, a halogen, etc.; R is H or a 1-4C alkyl; R is H, a halogen, etc.)], etc.; E is a group of formula III [Q is O or NR (R is H or a 1-4C alkyl); A is a 1-3C alkanediyl; R and R are each H or a halogen; R is a group of formula IV (Y is a 2-6C alkenediyl; R and R are each H, a 1-5C alkyl, etc.)]; R and R are each H, a halogen, etc.} or its pharmaceutically permissible salt, e.g. N-[1-[4-(1,1-dimethylethyl) phenyl]methylpiperidine-4-yl]-8-methoxy-4-[[4-[[[1-(phenylmethyl)piper idine-4- yl]amino]carbonyl]phenyl]amino-3-quinoline carboxamide. The compound can be produced e.g. by a process including the deprotonization of a compound of formula V, etc.

公开(公告)号：GR3033048T3

公开(公告)日：2000-08-31

申请号：GR20000400735

申请日：2000-03-24

Applicant: HOECHST AG

Inventor： HEITSCH HOLGER ,  WAGNER ADALBERT ,  WIRTH KLAUS ,  HROPOT MAX ,  BICKEL MARTIN

IPC: A61K31/00 ,  A61K31/33 ,  A61K31/335 ,  A61K31/395 ,  A61K31/47 ,  A61K31/4709 ,  A61K45/00 ,  A61K31/495 ,  A61K31/50 ,  A61K31/505 ,  A61K31/535 ,  A61K31/54 ,  A61P43/00

Abstract: Use of non-peptide bradykinin antagonists and their salts is claimed to treat chronic fibrogenetic liver disease (liver cirrhosis and liver fibrosis), acute liver disease and to prevent complications. Preferably the non-peptide bradykinin antagonist is a compound of formula (I). D-D' = X3=X2-X1=N, X4-C(R3)=N, N=C(R3)-X4, X4-CO-X4, CR3)=C(R3)-O; E = 1-4C alkyl, 1-4C alkylthio, 1-4C alkoxy (all optionally substituted by F), H, halo etc.; X1-X3 = N or optionally substituted CH; X4 = O, N or NR7; R1, R2 = H, halo, 1-4C alkyl or 1-4C alkoxy; R3 = H, halo, 1-6C alkyl, 6-12C aryl, (1-3C alkyl)(6-12C aryl), 3-5C alkenyl, 1-4C alkoxy, CO2H etc.

公开(公告)号：CA2232499A1

公开(公告)日：1998-09-27

申请号：CA2232499

申请日：1998-03-18

Applicant: HOECHST AG

Inventor： HEITSCH HOLGER ,  SCH LKENS BERNWARD ,  WIRTH KLAUS ,  WAGNER ADALBERT

IPC: C07D215/24 ,  A61K31/395 ,  A61K31/47 ,  A61K31/495 ,  A61P1/16 ,  A61P43/00 ,  C07D215/26 ,  C07D241/36 ,  C07D401/12 ,  C07D405/12 ,  C07D471/04 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D401/14

Abstract: Benzyloxy-substituted, fused N heterocycles, process for their preparation, and their use as bradykinin receptor antagonists The invention relates to compounds of the formula (I) (see fig. I) in which B, D, R1 and R2 have the meaning indicated in the patent claims, processes for their preparation and their use as therapeutics for the treatment and prevention of liver cirrhosis or Alzheimer's disease.

公开(公告)号：HRP970155A2

公开(公告)日：1998-04-30

申请号：HRP970155

申请日：1997-03-18

Applicant: HOECHST AG

Inventor： WAGNER ADALBERT ,  HEITSCH HOLGER ,  NOELKEN GERHARD ,  WIRT KLAUS ,  SCHOELKENS BERNWARD

IPC: C07D237/28 ,  A61K31/345 ,  A61K31/47 ,  A61K31/495 ,  A61K31/53 ,  A61P43/00 ,  C07D215/04 ,  C07D215/26 ,  C07D239/72 ,  C07D239/74 ,  C07D241/36 ,  C07D241/44 ,  C07D253/04 ,  C07D253/065 ,  C07D257/10

Abstract: Fluoroalkyl- and fluoroalkoxy-substituted benzyloxy-azaheterocyclic compounds of formula (I) and their salts are new: X1-X3 = N or CR ; R , R = H or halo; R , R = H, halo, 1-5C alkyl or 2-5C alkenyl; R = 2-5C alkenediyl, halo, OR , SR , NHR , -COOR or COOH; 1-6C alkyl, 6-12C aryl or 6-12C aryl-1-3C alkyl (all optionally substituted by e.g. OR , SR , NO2, CN, NHR or halo); R , R = H, 1-5C alkyl, 3-5C alkenyl or 6-12C aryl-1-3C alkyl; R = 1-5C alkyl or 1-5C alkoxy (both substituted by 1 or more F or Cl); B = amino acid; D = 2-5C alkanediyl, 1-5C alkanediyl or -(CH2)n-Yp-(CH2)m-; E = O or S; Y = O, S or NR ; n, m = 0-3; o = 1-3; and p = 0 or 1.

公开(公告)号：ID18447A

公开(公告)日：1998-04-09

申请号：ID971698

申请日：1997-05-21

Applicant: HOECHST AG

Inventor： HEITSCH HOLGER ,  WAGNER ADALBERT ,  WIRTH KLAUS ,  HROPOT MAX ,  BICKEL MARTIN

IPC: A61K31/00 ,  A61K45/00 ,  A61K31/33 ,  A61K31/335 ,  A61K31/395 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/50 ,  A61K31/505 ,  A61K31/535 ,  A61K31/54 ,  A61P43/00

Abstract: Use of non-peptide bradykinin antagonists and their salts is claimed to treat chronic fibrogenetic liver disease (liver cirrhosis and liver fibrosis), acute liver disease and to prevent complications. Preferably the non-peptide bradykinin antagonist is a compound of formula (I). D-D' = X3=X2-X1=N, X4-C(R3)=N, N=C(R3)-X4, X4-CO-X4, CR3)=C(R3)-O; E = 1-4C alkyl, 1-4C alkylthio, 1-4C alkoxy (all optionally substituted by F), H, halo etc.; X1-X3 = N or optionally substituted CH; X4 = O, N or NR7; R1, R2 = H, halo, 1-4C alkyl or 1-4C alkoxy; R3 = H, halo, 1-6C alkyl, 6-12C aryl, (1-3C alkyl)(6-12C aryl), 3-5C alkenyl, 1-4C alkoxy, CO2H etc.

公开(公告)号：SK32097A3

公开(公告)日：1998-01-14

申请号：SK32097

申请日：1997-03-11

Applicant: HOECHST AG

Inventor： HEITSCH HOLGER ,  WAGNER ADALBERT ,  WIRTH KLAUS ,  SCHOLKENS BERNWARD ,  NOLKEN GERHARD

IPC: A61K31/47 ,  A61P43/00 ,  C07D215/26 ,  C07D215/48 ,  A61K31/09

Abstract: 8-(3-(Aminoalkoxy)-benzyloxy)-quinoline compounds of formula (I) and their salts are new. R1-R3 = H, halo, CHO, COOH, 1-5C alkyl, 6-10C aryl, 1-3C alkyl-(6-10C) aryl, 3-8C cycloalkyl or 1-3C alkoxycarbonyl; R4, R5 = H, halo, NO2, CN, 1-3C alkoxy or 1-3C alkylthio; R6 = H, 1-3C alkyl, 3-5C alkylalkenyl (sic) or 1-3C alkyl-6-10C aryl; R7 = H, 1-6C alkanoyl, alkanoyl (substituted by 1-3C alkoxy, alkylcarbamoyl or aryl), 3-7C alkenoyl, 3-8C cycloalkylcarbonyl, 5-7C cycloalkenylcarbonyl, 1-3C alkoxycarbonyl, aryloxycarbonyl, 6-12C aroyl (optionally substituted by 1-3C alkoxy or halo), alkenoyl (substituted by aryl (optionally substituted by 1-3C alkoxy, 1-3C alkylenedioxy, NO2, CN, halo, 1-3C haloalkyl, hetero-3-8C cycloalkyl (sic), NH2, 1-4C alkylamino, 6-12C heteroaryl-alkanoylamino, aroylamino, 6-12C heteroarylcarbonylamino, 1-5C alkylsulphonylamino, 1-5C alkylureido, alkanoyl, 1-5C alkoxycarbonyl, 1-5C alkylcarbamoyl or arylcarbamoyl), 2-5C acylamino-arylcinnamoyl, 1-3C alkoxycarbonylamino-arylcinnamoyl, 1-4C alkylaminocarbonylaminocinnamoyl, aryl-1-5C alkoxycarbonyl, 1-5C alkylcarbamoyl, arylcarbamoyl, aroylcarbamoyl, alkylsulphonyl, arylsulphonyl, aryl-alkylsulphonyl or phthaloyl (for R6=R7(sic)); n = 1-8; alkyl has 1-6C, aryl has 6-12C, alkanoyl has 2-6C, and alkenoyl has 3-6C unless specified other wise.

公开(公告)号：CZ154697A3

公开(公告)日：1997-12-17

申请号：CZ154697

申请日：1997-05-20

Applicant: HOECHST AG

Inventor： HEITSCH HOLGER ,  WAGNER ADALBERT ,  WIRTH KLAUS ,  HROPOT MAX ,  BICKEL MARTIN

IPC: A61K45/00 ,  A61K31/00 ,  A61K31/33 ,  A61K31/335 ,  A61K31/395 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/50 ,  A61K31/505 ,  A61K31/535 ,  A61K31/54 ,  A61P43/00

Abstract: Use of non-peptide bradykinin antagonists and their salts is claimed to treat chronic fibrogenetic liver disease (liver cirrhosis and liver fibrosis), acute liver disease and to prevent complications. Preferably the non-peptide bradykinin antagonist is a compound of formula (I). D-D' = X3=X2-X1=N, X4-C(R3)=N, N=C(R3)-X4, X4-CO-X4, CR3)=C(R3)-O; E = 1-4C alkyl, 1-4C alkylthio, 1-4C alkoxy (all optionally substituted by F), H, halo etc.; X1-X3 = N or optionally substituted CH; X4 = O, N or NR7; R1, R2 = H, halo, 1-4C alkyl or 1-4C alkoxy; R3 = H, halo, 1-6C alkyl, 6-12C aryl, (1-3C alkyl)(6-12C aryl), 3-5C alkenyl, 1-4C alkoxy, CO2H etc.

公开(公告)号：MX9703725A

公开(公告)日：1997-11-29

申请号：MX9703725

申请日：1997-05-21

Applicant: HOECHST AG

Inventor： HEITSCH HOLGER ,  WAGNER ADALBERT ,  WIRTH KLAUS ,  HROPOT MAX ,  BICKEL MARTIN

IPC: A61K31/00 ,  A61K45/00 ,  A61K31/33 ,  A61K31/335 ,  A61K31/395 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/50 ,  A61K31/505 ,  A61K31/535 ,  A61K31/54 ,  A61P43/00 ,  C07D295/00

Abstract: La invencion se refiere a la aplicacion de antagonistas de bradiquinina no peptídicos para la preparacion de medicamentos para el tratamiento de enfermedades hepáticas cronicas y fibrogenéticas (cirrosis hepática y fibrosis hepática), de enfermedades hepáticas agudas, y para la prevencion de complicaciones, en especial para la profilaxis o el tratamiento de las hipertonías portales, de los fenomenos de descompensacion, tales como ascitis, formacion de edemas, síndrome hepatorrenal, gastropatías y colopatías hipertensoras, esplenomegalia, así como complicaciones hemorrágicas en el tracto gastrointestinal por hipertonía portal, circulacion colateral e hiperemia, y de una cardiopatía como consecuencia de una situacion circulatoria hiperdinámica cronica, y de sus consecuencias.

公开(公告)号：ZA974416B

公开(公告)日：1997-11-24

申请号：ZA974416

申请日：1997-05-21

Applicant: HOECHST AG

Inventor： WAGNER ADALBERT ,  HEITSCH HOLGER ,  NOELKEN GERHARD ,  WIRTH KLAUS ,  SCHOELKENS BERNWARD

IPC: C07D277/60 ,  A61K31/38 ,  A61K31/395 ,  A61K31/41 ,  A61K31/425 ,  A61K31/428 ,  A61K31/53 ,  A61P43/00 ,  C07D253/10 ,  C07D277/62 ,  C07D277/64 ,  C07D277/66 ,  C07D277/68 ,  C07D277/70 ,  C07D277/74 ,  C07D277/82 ,  C07D417/12 ,  C07D ,  A61K

Abstract: Sulphur-containing bradykinin antagonist compounds of formula (I) and their salts are claimed: one of X1-X3 = COR , and the other X1-X4 = N, CR ; R ,R = H, halo, 1-6C alkyl, OR , SR , NHR , 6-12C aryl, (6-12C aryl)(1-3C alkyl), C(O)OR , C(O)H, 2-5C alkenyl, NO2, SO3R , CN, C(O)NHR , where alkyl, aryl, alkenyl may be substituted by C(O)(O)o(1-5C alkyl), OR , SR , NO2, CN, NHR , halo; R = (II); R ,R = e.g. H; R -R = H, 1-5C alkyl, 3-5C alkenyl, etc.; A = amino acid e.g. methionine, alanine, phenylalanine, etc.; R = H, C(O)(O)o(1-5C alkyl), C(O)(O)o(11-3C alkyl)(6-10C aryl); R = e.g. C(O)DE; D = 2-5C alkendiyl, 1-8C alkandiyl, (CH2)nYo(CH2)m, etc., where any of the groups are optionally substituted by e.g. OR ; E = H, 6-10C aryl, 1-9C heteroaryl, etc.;Y = O, S, NR ; n,m = 0-6; o = 0 or 1.

公开(公告)号：NO972311L

公开(公告)日：1997-11-24

申请号：NO972311

申请日：1997-05-21

Applicant: HOECHST AG

Inventor： HEITSCH HOLGER ,  WAGNER ADALBERT ,  WIRTH KLAUS ,  HROPOT MAX ,  BICKEL MARTIN

IPC: A61K31/00 ,  A61K31/33 ,  A61K45/00 ,  A61K31/335 ,  A61K31/395 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/50 ,  A61K31/505 ,  A61K31/535 ,  A61K31/54 ,  A61P43/00

Abstract: Use of non-peptide bradykinin antagonists and their salts is claimed to treat chronic fibrogenetic liver disease (liver cirrhosis and liver fibrosis), acute liver disease and to prevent complications. Preferably the non-peptide bradykinin antagonist is a compound of formula (I). D-D' = X3=X2-X1=N, X4-C(R3)=N, N=C(R3)-X4, X4-CO-X4, CR3)=C(R3)-O; E = 1-4C alkyl, 1-4C alkylthio, 1-4C alkoxy (all optionally substituted by F), H, halo etc.; X1-X3 = N or optionally substituted CH; X4 = O, N or NR7; R1, R2 = H, halo, 1-4C alkyl or 1-4C alkoxy; R3 = H, halo, 1-6C alkyl, 6-12C aryl, (1-3C alkyl)(6-12C aryl), 3-5C alkenyl, 1-4C alkoxy, CO2H etc.