公开(公告)号：JPH10279563A

公开(公告)日：1998-10-20

申请号：JP7942398

申请日：1998-03-26

Applicant: HOECHST AG

Inventor： HEITSCH HOLGER DR ,  WAGNER ADALBERT DR ,  WIRTH KLAUS DR ,  SCHOLKENS BERNWARD

IPC: C07D215/24 ,  A61K31/395 ,  A61K31/47 ,  A61K31/495 ,  A61P1/16 ,  A61P43/00 ,  C07D215/26 ,  C07D241/36 ,  C07D401/12 ,  C07D405/12

Abstract: PROBLEM TO BE SOLVED: To obtain a novel compound that has high affinity to bradykinin receptor and improved pharmacodynamic effect and is useful for treatment and prevention of hepatocirrhosis and Alzheimer's disease. SOLUTION: This novel compound is represented by formula I D is formula II [X is N, C-R (R is H, a halogen, a lower alkyl; X is N), C-R (R is H, a lower alkyl, an alkenyl; X is N), C-R (R is same as R )]; B is formula III (R and R are each H, a halogen, cyano; R is nitro, amino); R and R are each H, a halogen, a 1-3C alkyl}, typically 8-[6-chloro-2-cyano-3-(N- ethylaminocarbonylglycyloxy)-2-methylquinoline. The objective compound is prepared by reaction of a compound of formula IV with a compound of formula V in an inert solvent in the presence of a metal hydride or an alkali metal carbonate at 0-60 deg.C.

公开(公告)号：JPH10130163A

公开(公告)日：1998-05-19

申请号：JP27830197

申请日：1997-10-13

Applicant: HOECHST AG

Inventor： HEITSCH HOLGER DR ,  HENKE STEPHAN DR ,  BREIPOHL GERHARD DR ,  KNOLLE JOCHEN DR ,  WIRTH KLAUS DR ,  WIEMER GABRIELE

IPC: A61K38/00 ,  A61K38/04 ,  A61K38/22 ,  A61K45/00 ,  A61P25/28 ,  A61P43/00 ,  C07K7/06 ,  C07K7/18

Abstract: PROBLEM TO BE SOLVED: To obtain an agent useful for the treatment and prevention of Alzheimer's disease by using a bradykinin antagonistic agent (or its physiologically permissible salt) as an active component,. SOLUTION: A bradykinin antagonistic agent (or its physiologically permissible salt) consisting of e.g. a peptide of the formula H-D-Arg-Arg-Pro-Hyp-Gly- Thi-Ser-D-Tic-Oic-Arg-OH (HOE 140) [the abbreviations of the amino acids correspond to conventional 3-letter codes of peptide chemistry described in Europ.J.Biochem.138,9(1984) and the others are Oic: cis, endo-octahydroindole-2- carbonyl; Thi: 2-thienylalanyl; Tic: 1,2,3,4-tetrahydroisoquinolin-3-ylcarbonyl] is used as an agent for the treatment and prevention of Alzheimer's disease. It can be administered by oral, parenteral, nasal, transrectal or respiratory administration in the form suitable for the administration method.

公开(公告)号：JPH107656A

公开(公告)日：1998-01-13

申请号：JP6474897

申请日：1997-03-18

Applicant: HOECHST AG

Inventor： WAGNER ADALBERT DR ,  HEITSCH HOLGER DR ,  NOELKEN GERHARD DR ,  WIRTH KLAUS DR ,  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: PROBLEM TO BE SOLVED: To obtain fluoroalkyl- and fluoroalkoxy-substituted heterocyclic bradykinin antagonists that have bradykinin antagonism and extremely long duration of efficacy. SOLUTION: The fluoroalkyl- and fluoroalkoxy-substituted heterocyclic bradykinin antagonists are heterocyclic fluoroalkyl or fluoroalkoxy derivatives of formula I [X1 -X3 are each N or a CR (R is H, a halogen, a 1-5C alkyl, etc.); R and R are each H or a halogen; R and R are each H, a halogen, 1-5C alkyl or 2-5C alkenyl; R is H, a 1-5C alkyl, 3-5C alkenyl, etc.; R is a 1-5C alkyl Hs of which are all or partly replaced with a F or Cl atom, etc.; B is an aminocarboxylic group; D is a 2-5 alkenediyl, 1-5C alkanediyl, etc.; E is O or S; o is a number of 1-3], or their biologically tolerable salts, for example, 8-[3-(N-(4-trans-trifluoromethylcinnamoylglycyl)-N-methylamino)-2,6- dichlorobenzyloxy]-2-methylquinoline. The compounds of formula I can be synthesized using a compound of formula II as a synthetic material.

公开(公告)号：JPH1067762A

公开(公告)日：1998-03-10

申请号：JP13116197

申请日：1997-05-21

Applicant: HOECHST AG

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

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

Abstract: PROBLEM TO BE SOLVED: To produce a sulfur-containing compound which is a strong bradykinin antagonist and useful for treating and/or preventing allergies, inflammations, autoimmune diseases, shocks and pains. SOLUTION: This compound is represented by formula I one of X1 to X3 is C-O-R [R is a group represented by formula II (R and R are each H, a halogen, CN, etc.; R is H, a 1-5C alkyl, etc.; A is an aminocarboxyluc acid; R is H, etc.)]; others and X4 are N or CR (R is H, a halogen, etc.); R is same as R } and its physiologically permissible salt, e.g. 4-[3-(N-(3- methoxycinnamoylglycyl)-N-methylamino)-2,6-dichlorobenzyloxy]benzothia zole. The compound represented by formula I can be produced by passing a compound represented by formula III as a starting raw material through specific steps. Thereby, a pharmaceutical preparation for treating and/or preventing diseases caused by a mediator such as prostaglandins or leukotrienes.

公开(公告)号：JPH101472A

公开(公告)日：1998-01-06

申请号：JP5783497

申请日：1997-03-12

Applicant: HOECHST AG

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

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

Abstract: PROBLEM TO BE SOLVED: To obtain the subject compound useful as a bradykinin receptor antagonist, having high affinity for a bradykinin B2 receptor and improved water solubility. SOLUTION: This compound is shown by formula I (R to R are each a 1-5C alkyl, a 6-10C aryl, a halogen, H, CHO, etc.; R and R are each H, a halogen, a 1-3C alkoxy, nitro, etc.; (n) is 1 to 8; R is H, a 1-3C alkyl, etc.; R is H, an acyl, etc.) such as 8-[3-(2-aminoethoxy)-2,6-dichlorobenzyloxy]-2- methylquinoline. The compound of formula I is obtained, for example, by reacting a compound of formula II with a compound of formula III to give a compound of formula IV and then hydrolyzing the reaction product with hydrazine. The compound of formula I is useful for treating and preventing allergy, inflammation, autoimmune disease, shock, pain, etc.

公开(公告)号：ES2196207T3

公开(公告)日：2003-12-16

申请号：ES97103611

申请日：1997-03-05

Applicant: HOECHST AG

Inventor： WAGNER ADALBERT DR ,  HEITSCH HOLGER DR ,  NOLKNE GERHARD DR ,  WIRTH KLAUS DR ,  BERNARD PROF-DR

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：DK0796848T3

公开(公告)日：2003-09-22

申请号：DK97103611

申请日：1997-03-05

Applicant: HOECHST AG

Inventor： WAGNER ADALBERT DR ,  WIRTH KLAUS DR ,  HEITSCH HOLGER DR ,  NOELKNE GERHARD DR ,  BERNARD PROF-DR

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：DK0836853T3

公开(公告)日：2003-04-14

申请号：DK97117540

申请日：1997-10-10

Applicant: HOECHST AG

Inventor： BREIPOHL GERHARD DR ,  WIRTH KLAUS DR ,  HEITSCH HOLGER DR ,  HENKE STEPHAN DR ,  KNOLLE JOCHEN DR ,  WIEMER GABRIELE PROF DR

IPC: A61K38/00 ,  A61K38/04 ,  A61K38/22 ,  A61K45/00 ,  A61P25/28 ,  A61P43/00 ,  C07K7/06 ,  C07K7/18

Abstract: Use of bradykinin antagonists, or their salts, to treat or prevent Alzheimer's disease, is new

公开(公告)号：SI0795547T1

公开(公告)日：2000-10-31

申请号：SI9730063

申请日：1997-02-27

Applicant: HOECHST AG

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

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

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：ES2148858T3

公开(公告)日：2000-10-16

申请号：ES97103163

申请日：1997-02-27

Applicant: HOECHST AG

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

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

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.