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：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：ES2205086T3

公开(公告)日：2004-05-01

申请号：ES97107623

申请日：1997-05-09

Applicant: HOECHST AG

Inventor： WAGNER ADALBERT DR ,  HEITSCH HOLGER DR ,  NOLKEN GERHARD DR ,  WIRTH KLAUS DR ,  SCHOLKENS 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: 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：AT247644T

公开(公告)日：2003-09-15

申请号：AT92115500

申请日：1992-09-10

Applicant: HOECHST AG

Inventor： HEITSCH HOLGER DR ,  WAGNER ADALBERT DR ,  KLEEMANN HEINZ-WERNER DR ,  GERHARDS HERMANN DR ,  SCHOELKENS BERNWARD PROF DR

IPC: A61K31/33 ,  A61K31/415 ,  A61K31/4184 ,  A61K31/435 ,  A61K31/4375 ,  A61K31/44 ,  A61K31/495 ,  A61K31/505 ,  A61P9/10 ,  A61P9/12 ,  C07D235/06 ,  C07D235/08 ,  C07D235/22 ,  C07D235/24 ,  C07D403/10 ,  C07D409/06 ,  C07D471/04 ,  C07D487/04 ,  C07D519/00

Abstract: Compounds of the formula (I) in which the symbols have the following meaning: X represents a monocyclic radical having 3, 4 or 5 ring atoms, R , R , R , R , R , R and R is, for example, an alkyl radical q is zero or 1 L is, for example, the methylene group A is the radical, for example, of a heterocycle are highly effective as antagonists of angiotensin II receptors. They can be used as pharmaceuticals or diagnostics.

公开(公告)号：AT230732T

公开(公告)日：2003-01-15

申请号：AT93103301

申请日：1993-03-02

Applicant: HOECHST AG

Inventor： HEITSCH HOLGER DR ,  HENNING RAINER DR ,  WAGNER ADALBERT DR ,  GERHARDS HERMANN DR ,  BECKER REINHARD DR ,  SCHOELKENS BERNWARD PROF DR

IPC: A61K31/415 ,  A61K31/4164 ,  A61K31/64 ,  A61P9/10 ,  A61P9/12 ,  C07D233/84 ,  C07D233/86 ,  C07D233/90

Abstract: Compounds of the formula (I) in which R is, for example, ethyl, R is, for example, methyl, n is, for example, zero, R is, for example, COOH and R is, for example, SO2NHCONHCH3 are highly active antagonists of angiotensin II receptors.

公开(公告)号：BR9801132A

公开(公告)日：2000-03-21

申请号：BR9801132

申请日：1998-03-26

Applicant: HOECHST AG

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

IPC: C07D215/24 ,  A61K31/395 ,  A61K31/47 ,  A61K31/495 ,  A61P1/16 ,  A61P43/00 ,  C07D215/26 ,  C07D241/36 ,  C07D401/12 ,  C07D405/12 ,  A61K31/425 ,  C07D277/64

Abstract: 8-Benzyloxy-(iso)quinoline derivatives (including poly-aza analogues) of formula (I) and their salts are new: D = aza-heterocyclic residue of formula (i) or (ii); X1 = N or CR6; X2 = N or CR7; X3 = N or CR8; B = benzyl variably substituted on the ring by R3-R5; R1, R2 = H, halo or 1-3C alkyl; R3, R4 = H, halo, CN, 1-3C alkyl (optionally substituted by halo), 1-3C alkoxy (optionally substituted by halo), 1-3C alkylthio (optionally substituted by halo), OH, tetrazolyl, CONHR9 or CO2R9; R5 = NO2, NH2, -NR9AYER10 or SO2NR9R10; R6, R8, R'" = H, halo, 1-4C alkyl, 1-4C alkoxy, NH2, NH-(1-4C alkyl), OH, Ar, Ar-(1-4C)-alkanediyl or CO2R9; R7, R', R" = H or 1-4C alkyl; R9 = H, 1-4C alkyl, 2-5C alkenyl or Ar-(1-3C)-alkanediyl; A = divalent residue of an aminocarboxylic acid such as methionine, alanine, phenylalanine, tyrosine, O-methyltyrosine, beta -(2-thienyl)-alanine, glycine, cyclohexylalanine, leucine, isoleucine, valine, norleucine, phenylglycine, serine, cysteine, aminopropionic acid or aminobutyric acid; Y = C=O, C=S or SO2; E = 2-5C alkene-diyl, 1-7C alkanediyl, 3-10C cycloalkanediyl or -(CH2)m-To-(CH2)n (all optionally substituted by one or more groups such as OR12, NO2, CN, CO2R9, NR13R14, SO3R12, SO2NR13R14 or CONR13R14); T = O, S or NR15; m, n = 0-6; o = 0 or 1; p = 1-3; R10 = H or 1-5C alkyl, Ar', Ar'-(1-3C)-alkanediyl or 5-10C heteroaryl (all optionally substituted by one or more groups such as halo, NO2, 1-5C alkylthio, NR13R14, NR13COR16, CO2R9, SO3R12, SO2NR13R14, OR12 or 1-6C alkyl, or Ar', 2-5C alkenyl or OA5 (themselves optionally partially or completely substituted by halo)); R11 = 1-5C alkyl or 1-5C alkoxy (both optionally partially or completely substituted by F or Cl); R12, R13 = H, 1-5C alkyl, 2-5C alkenyl, Ar, Ar-(1-5C)-alkanediyl, 3-10C cycloalkyl, (3-10C)-cycloalkyl-(1-2C)-alkanediyl, CO2-(1-5C alkyl) or CONH-(1-5C alkyl); R14 = H, CO2-(1-3C alkyl) or CO2-(1-3C)-alkanediyl-Ar'; R15 = H, CO2-(1-3C alkyl) or 1-3C alkyl; R16 = 1-3C alkyl, Ar or 5-10C heteroaryl (all optionally substituted by one or more groups such as halo, CN, NO2, NR13R14 or CO2R9); Ar, Ar' = aryl with 6-12C or 6-10C respectively; provided that if D = (ii), then R3 and R4 are not both halo, 1-3C and/or 1-3C alkoxy or H in combination with halo, 1-3C alkyl or 1-3C alkoxy, excluded from this proviso being compounds in which: (a) R5 = -N(R9)-A-Y-E-R10 and R10 = (R11)p-substituted phenyl, provided that if R10 = (R11)p-substituted phenyl then R3 and R4 are not same or different H and halo; and (b) R5 = -SO2NR9R10, provided that R3 and R4 are not both halo.

公开(公告)号：DK0606065T3

公开(公告)日：2000-03-13

申请号：DK94100048

申请日：1994-01-04

Applicant: HOECHST AG

Inventor： WAGNER ADALBERT DR ,  BHATNAGAR NEERJA DR ,  BUENDIA JEAN DR ,  GRIFFOUL CHRISTINE DR

IPC: B01J23/44 ,  A61K31/235 ,  A61K31/41 ,  C07B37/04 ,  C07B61/00 ,  C07C41/48 ,  C07C45/61 ,  C07C45/71 ,  C07C47/546 ,  C07C67/30 ,  C07C67/343 ,  C07C69/76 ,  C07C69/767 ,  C07C253/30 ,  C07C255/37 ,  C07C255/40 ,  C07C255/56 ,  C07C303/40 ,  C07C311/09 ,  C07C311/48 ,  C07C311/51 ,  C07C311/52 ,  C07C311/53 ,  C07C311/54 ,  C07C311/57 ,  C07C311/58 ,  C07D257/04

Abstract: The invention relates to a method for the preparation of a compound of the general formula (I) in which X represents an optionally protected formyl group and R denotes a group which is itself inert to the reaction conditions of the synthesis, for example -CN, characterised in that a compound of the general formula (II) where X is as defined above, is reacted with a substituted phenyl halogen compound of the formula (III) where Hal denotes e.g. bromine. The compounds are useful intermediates for pharmaceutical synthesis.

公开(公告)号：AT165351T

公开(公告)日：1998-05-15

申请号：AT91122406

申请日：1992-01-01

Applicant: HOECHST AG

Inventor： WAGNER ADALBERT DR ,  ENGLERT HEINRICH DR ,  KLEEMANN HEINZ-WERNER DR ,  GERHARDS HERMANN DR ,  SCHOELKENS BERNWARD PROF DR ,  BECKER REINHARD DR ,  LINZ WOLFGANG DR ,  CAILLE JEAN-CLAUDE ,  VEVERT JEAN-PAUL

IPC: A61K31/40 ,  A61K31/415 ,  A61K31/425 ,  A61K31/435 ,  A61K31/44 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/505 ,  A61K31/535 ,  A61K31/54 ,  A61K31/64 ,  A61P9/00 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  A61P13/02 ,  A61P15/00 ,  A61P43/00 ,  C07D207/34 ,  C07D207/36 ,  C07D233/54 ,  C07D233/66 ,  C07D233/68 ,  C07D233/70 ,  C07D233/84 ,  C07D233/90 ,  C07D249/02 ,  C07D255/02 ,  C07D257/02 ,  C07D257/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D453/02 ,  C07D521/00

Abstract: Azole derivative of the general formula (I) in which A, L, O, R , X, Y, Z and q have the meanings given, a process for their preparation, pharmaceutical preparations and the use of the compounds are described. Azole derivatives of the formula I where the symbols have, for example, the following meanings: R = (C2-C10)-alkyl Z = nitrogen X and Y = independently of one another CR L = -CH2- q = zero or 1 A = biphenyl radical which is substituted, for example, by R R = halogen or hydrogen R = SO2-NH-CO-OR and R = phenyl, are highly active antagonists of angiotensin II receptors.