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：DE19546938A1

公开(公告)日：1997-06-19

申请号：DE19546938

申请日：1995-12-15

Applicant: HOECHST AG

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

IPC: A61K38/00 ,  C07K5/02 ,  C07K7/18 ,  A61K38/06 ,  A61K38/07

Abstract: 1-Carbamoyl-4-piperidinecarbonyl di- and tripeptides (I) and their salts are new: R = H, 2-6C alkyl, NR R or -N(R )=C(NHR )(NHR ); R = 1-10C alkyl, 2-10C alkenyl, 3-10C alkynyl or -(CH2)m-B-(CH2)n-R (all optionally monosubstituted by CO2R or by 1 or more halo), OR , 3-8C cycloalkyl, 4-10C cycloalkyl-1-4C alkyl, 5-10C cycloalkyl-2-4C alkenyl, 5-10C cycloalkyl-2-4C alkynyl or 6-10C aryl (optionally mono- or disubstituted by halo, 1-4C alkoxy, NO2 or CN); R = H, 1-8C alkyl, 3-8C cycloalkyl, phenyl, benzyl, 1-8C alkoxy-CO- or 1-4C alkyl-6-10C aryloxy-CO-; R = H, 1-6C alkyl, 3-8C cycloalkyl, 2-4C alkenyl or 2-4C alkynyl; R = H, 1-6C alkyl, 3-8C cycloalkyl, phenyl or benzyl; B = O, NR or S; n = 1-5; m = 0-5; o, p = 1-10; A1 = a bond, Phe, 2-, 3- or 4-Cl- or 2-, 3- or 4-F-phenylalanine, Tyr, Tyr(OMe), Thi, Gly, Cha, Leu, Ile, Val, Nle or Phg; A2 = a bond, Gly, Ser, Hser, Lys, Leu, Val, Nle, Ile or Cys; and A3, A4 = a bond or a heterocyclic group of e.g. formula (A) to (C).

公开(公告)号：DK0795547T3

公开(公告)日：2000-09-18

申请号：DK97103163

申请日：1997-02-27

Applicant: HOECHST AG

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

公开(公告)号：DE19610784A1

公开(公告)日：1997-09-25

申请号：DE19610784

申请日：1996-03-19

Applicant: HOECHST AG

Inventor： WAGNER ADALBERT DR ,  HEITSCH HOLGER DR ,  NOELKEN GERHARD DR ,  WIRTH KLAUS DR ,  SCHOELKENS BERNWARD 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 ,  C07D237/30 ,  C07D241/40 ,  C07D253/10 ,  C07D257/12 ,  C07C205/07

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：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：AT192738T

公开(公告)日：2000-05-15

申请号：AT97103163

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: 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.

公开(公告)号：AT252567T

公开(公告)日：2003-11-15

申请号：AT97107623

申请日：1997-05-09

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: 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：GR3033415T3

公开(公告)日：2000-09-29

申请号：GR20000401105

申请日：2000-05-16

Applicant: HOECHST AG

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