公开(公告)号：JP2004189755A

公开(公告)日：2004-07-08

申请号：JP2004087016

申请日：2004-03-24

Applicant: Hoechst Ag ,  ヘキスト・アクチェンゲゼルシャフト

Inventor： LANG HANS-JOCHEN ,  WEICHERT ANDREAS ,  KLEEMANN HEINZ-WERNER ,  SCHWARK JAN ROBERT ,  SCHOLZ WOLFGANG ,  ALBUS UDO

IPC: A61K31/165 ,  A61K31/155 ,  A61K31/166 ,  A61K31/44 ,  A61K31/47 ,  A61K31/472 ,  A61P1/04 ,  A61P1/16 ,  A61P3/10 ,  A61P7/02 ,  A61P9/00 ,  A61P9/02 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  A61P11/00 ,  A61P13/08 ,  A61P13/12 ,  A61P35/00 ,  A61P43/00 ,  C07C233/65 ,  C07C277/08 ,  C07C279/18 ,  C07C279/22 ,  C07D213/30 ,  C07D213/56 ,  C07D215/14 ,  C07D215/50 ,  C07D217/18 ,  C07D217/24

CPC classification number: C07C279/22 ,  Y10S514/821

Abstract: PROBLEM TO BE SOLVED: To provide a substituted benzoylguanidine compound useful for treating cardiovascular diseases, such as arrhythmia, and other diseases.
SOLUTION: The compound is a substituted benzoylguanidine represented by formula I [wherein, R(1) and R(2) are H, Hal, (cyclo)alkyl, N
3 , CN or OH, alkyloxy, phenyl, phenoxy or benzoyl; and R(3) is H] and its pharmacologically acceptable salts (except compounds of benzoylguanidine 4-chlorobenzoylguanidine, 3,4-dichlorobenzoylguanidine and 3- or 4-methylbenzoylguanidine).
COPYRIGHT: (C)2004,JPO&NCIPI

公开(公告)号：JPH0952823A

公开(公告)日：1997-02-25

申请号：JP19628396

申请日：1996-07-25

Applicant: HOECHST AG

Inventor： SCHWARK JAN-ROBERT ,  BRENDEL JOACHIM ,  KLEEMANN HEINZ-WERNER ,  LANG HANS JOCHEN ,  WEICHERT ANDREAS ,  ALBUS UDO ,  SCHOLZ WOLFGANG

IPC: C07C279/20 ,  A01N1/02 ,  A61K31/155 ,  A61K31/16 ,  A61K31/275 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/4418 ,  A61P3/08 ,  A61P3/10 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P11/00 ,  A61P13/02 ,  A61P15/00 ,  A61P35/00 ,  C07C277/08 ,  C07C279/22 ,  C07C323/62 ,  C07D213/65 ,  C07D213/70

Abstract: PROBLEM TO BE SOLVED: To obtain a substituted cinnamoyl guanidide useful as a therapeutic or diagnostic agent for cardiovascular diseases such as arrhythmia, myocardial infarction and stenocardia. SOLUTION: This substituted compound (salt) is expressed by formula I [R(1)-R(5) (X is CR(16), O, S, etc.; R(16) is H, a 1-4C alkyl, etc.; Y is a 1-8C alkylene, etc.; L is O, S, etc.; U is NR(24)R(25), N-contg. heterocycle, etc.; R(24) and R(25) are each H, a 1-4C alkyl, etc.; (a), (b) and (n) are each 0 or 1; R(6) and R(7) are each H, Cl, Br, I, CN, a 1-8C alkyl, etc.]. This compound is obtained by reaction of a compound of formula II (L is a nucleophilically substituent eliminable group) with guanidine. This compound of formula I is e.g. E-3-(4- dimethylaminophenyl)-2-methyl-propenoyl guanidide. This compound can be administered orally or parenterally, that is, intravenously, intrarectally or imhaledly, its dose being 0.1-10mg/kg.

公开(公告)号：JPH06345715A

公开(公告)日：1994-12-20

申请号：JP12161694

申请日：1994-06-03

Applicant: HOECHST AG

Inventor： SCHWARK JAN-ROBERT ,  KLEEMANN HEINZ-WERNER ,  LANG HANS-JOCHEN ,  WEICHERT ANDREAS ,  SCHOLZ WOLFGANG ,  ALBUS UDO

IPC: A61K31/165 ,  A61K31/155 ,  A61K31/166 ,  A61K31/395 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4418 ,  A61P9/00 ,  A61P9/06 ,  A61P9/10 ,  A61P43/00 ,  C07C277/08 ,  C07C279/22 ,  C07C311/15 ,  C07C317/32 ,  C07C317/44 ,  C07C317/48 ,  C07C323/62 ,  C07D207/337 ,  C07D213/30 ,  C07D213/53 ,  C07D213/54 ,  C07D213/58 ,  C07D213/65 ,  C07D215/14 ,  C07D217/16 ,  C07D231/12 ,  C07D233/06 ,  C07D233/61 ,  C07D233/64 ,  C07D241/26 ,  C07D241/28

公开(公告)号：JPH07109251A

公开(公告)日：1995-04-25

申请号：JP20158594

申请日：1994-08-26

Applicant: HOECHST AG

Inventor： WEICHERT ANDREAS ,  LANG HANS-JOCHEN ,  KLEEMANN HEINZ-WERNER ,  SCHWARK JAN-ROBERT ,  SCHOLZ WOLFGANG ,  ALBUS UDO

IPC: A61K31/155 ,  A61K31/4164 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P13/02 ,  A61P15/00 ,  A61P25/00 ,  A61P43/00 ,  C07C233/78 ,  C07C235/50 ,  C07C237/34 ,  C07C279/22 ,  C07C323/60 ,  C07D233/54 ,  C07D233/60 ,  C07D233/61

公开(公告)号：WO9746226A3

公开(公告)日：1998-03-05

申请号：PCT/EP9702548

申请日：1997-05-20

Applicant: HOECHST AG ,  LANG HANS JOCHEN ,  JANSEN HANS WILLI ,  SCHWARK JAN ROBERT ,  KLEEMANN HEINZ WERNER ,  JUNG OLIVER ,  SCHAEFER HANS LUDWIG ,  LINZ WOLFGANG ,  KRAMER WERNER ,  SCHOELKENS BERNWARD ,  FALK EUGEN

Inventor： LANG HANS JOCHEN ,  JANSEN HANS-WILLI ,  SCHWARK JAN-ROBERT ,  KLEEMANN HEINZ-WERNER ,  JUNG OLIVER ,  SCHAEFER HANS-LUDWIG ,  LINZ WOLFGANG ,  KRAMER WERNER ,  SCHOELKENS BERNWARD ,  FALK EUGEN

IPC: A61K31/155 ,  A61K31/00 ,  A61K31/166 ,  A61K31/22 ,  A61K31/255 ,  A61K31/365 ,  A61K31/41 ,  A61K31/455 ,  A61K45/00 ,  A61K45/06 ,  A61P3/00 ,  A61P3/06 ,  A61P9/00 ,  A61P9/10 ,  A61P43/00

CPC classification number: A61K31/166 ,  A61K31/00 ,  A61K31/155 ,  A61K31/22 ,  A61K31/365 ,  A61K31/165 ,  A61K2300/00

Abstract: The active substances identified as inhibitors of the cellular Na+/H+ exchanger (NHE) are used to prepare a medicament for normalizing serum lipids. They are used in the preparation of a medicament which reduces lipid levels in the blood and can be administered for treating diseases caused by lipid levels which are too high, and for alleviating the endothelial dysfunctional syndrome and for treating diseases caused thereby.

Abstract translation: 被鉴定为细胞Na + / H +交换剂（NHE）的抑制剂的活性物质用于制备用于使血清脂质正常化的药物。 它们用于制备降低血液中脂质水平并且可以用于治疗由过高的脂质水平引起的疾病以及用于缓解内皮功能障碍综合征和用于治疗由此引起的疾病的药物的药物。

公开(公告)号：JP2002105043A

公开(公告)日：2002-04-10

申请号：JP2001224010

申请日：2001-07-25

Applicant: HOECHST AG

Inventor： KLEEMANN HEINZ-WERNER ,  LANG HANS-JOCHEN ,  WEICHERT ANDREAS ,  CRAUSE PETER ,  SCHOLZ WOLFGANG ,  ALBUS UDO

IPC: A61K31/155 ,  A61K31/185 ,  A61P9/00 ,  A61P9/10 ,  C07C277/08 ,  C07C279/20 ,  C07C279/22 ,  C07C311/37 ,  C07C311/59 ,  C07C315/04 ,  C07C317/32 ,  C07C317/44 ,  C07C323/65 ,  C07C323/67 ,  C07D207/327 ,  C07D215/54 ,  C07D231/12 ,  C07D233/60 ,  C07D233/61 ,  C07D295/10 ,  C07D295/155 ,  C07D521/00

Abstract: PROBLEM TO BE SOLVED: To provide an intermediate compound for producing a diacyl- substituted guanidine useful as a Na+/H+ exchange inhibitor. SOLUTION: This intermediate compound is a compound of the formula III [wherein, X(2) is a group as shown in the formula (a)]. As an example of the compound of the formula III, 4-isopropyl-3-methylsulfonylbenzoylguanidine and 4-fluoro-3-trifluoromethylbenzoylguanidine are cited. As the method for producing them, a method of reacting an acid chloride of a corresponding benzoic acid with guanidine hydrochloride in the presence of a base is exemplified. The diacylguanidine used as a medicine is obtained by reacting the compound of the formula III with a prescribed benzoic acid derivative.

公开(公告)号：JPH08225514A

公开(公告)日：1996-09-03

申请号：JP30416395

申请日：1995-11-22

Applicant: HOECHST AG

Inventor： SCHWARK JAN-ROBERT ,  KLEEMANN HEINZ-WERNER ,  LANG HANS-JOCHEN ,  WEICHERT ANDREAS ,  SCHOLZ WOLFGANG ,  ALBUS UDO

IPC: A61K31/165 ,  A61K31/095 ,  A61K31/155 ,  A61K31/18 ,  A61K31/33 ,  A61K31/40 ,  A61K31/41 ,  A61K31/435 ,  A61K31/535 ,  A61K31/54 ,  A61P1/16 ,  A61P3/08 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  A61P11/00 ,  A61P13/02 ,  A61P15/00 ,  A61P35/00 ,  A61P43/00 ,  C07C277/08 ,  C07C279/12 ,  C07C279/22 ,  C07C317/44 ,  C07C321/28 ,  C07C323/62 ,  C07D207/00 ,  C07D211/00 ,  C07D213/00 ,  C07D215/00 ,  C07D217/12 ,  C07D233/00 ,  C07D239/00 ,  C07D241/00 ,  C07D261/00 ,  C07D263/00 ,  C07D265/00

公开(公告)号：CA2546602C

公开(公告)日：2008-10-28

申请号：CA2546602

申请日：1994-08-23

Applicant: HOECHST AG

Inventor： CRAUSE PETER ,  KLEEMANN HEINZ-WERNER ,  WEICHERT ANDREAS ,  LANG HANS-HOCHEN ,  SCHOLZ WOLFGANG ,  SCHWARK JAN-ROBERT ,  ALBUS UDO

IPC: A61K31/155 ,  C07C279/02 ,  A61K31/16 ,  A61K31/185 ,  A61K31/4164 ,  A61K31/47 ,  A61P9/00 ,  A61P9/10 ,  C07C277/08 ,  C07C279/20 ,  C07C279/22 ,  C07C311/37 ,  C07C311/59 ,  C07C315/04 ,  C07C317/32 ,  C07C317/44 ,  C07C323/65 ,  C07C323/67 ,  C07D207/327 ,  C07D215/54 ,  C07D231/12 ,  C07D233/60 ,  C07D233/61 ,  C07D295/10 ,  C07D295/155 ,  C07D521/00

Abstract: Monoacyl - substituted guanidines of the formula III (see formula III) are described where X(2) is (see formula I) as are the pharmaceutically tolerated salts thereof. They are outstandingly suitable for use as antiarrhythmic pharmaceuticals possessing a cardioprotective component for the prophylaxis and treatment of infarction and for the treatment of angina pectoris, in connection with which they also inhibit or strongly reduce, in a preventive manner, the pathophysiological processes associated with the genesis of ischemically induced damage, in particular associated with the elicitation of ischemically induced cardiac arrhythmias. On account of their protective effects against pathological hypoxic and ischemic situations, the compounds of the formula I according to the invention can, as a consequence of inhibiting the cellular Na+/H+ exchange mechanism, be used as pharmaceuticals for treating all acute or chronic damage eliciated by ischemia, or diseases induced primarily or secondarily thereby.

公开(公告)号：CA2152137C

公开(公告)日：2007-11-13

申请号：CA2152137

申请日：1995-06-19

Applicant: HOECHST AG

Inventor： SCHWARK JAN-ROBERT ,  KLEEMANN HEINZ-WERNER ,  LANG HANS-JOCHEN ,  WEICHERT ANDREAS ,  SCHOLZ WOLFGANG ,  ALBUS UDO

IPC: A61K31/165 ,  C07C279/22 ,  A01N1/02 ,  A61K31/16 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  A61P31/04 ,  A61P35/00 ,  A61P37/08 ,  C07C277/08

Abstract: Phenyl-substituted alkenylcarboguanidides carrying perfluoroalkyl groups, of the formula I (see Formula I) in which the substituents have the meanings stated in the description, and their pharmaceutically suitable salts, are described. They are obtained by reacting a compound II (see Formula II) with guanidine, in which R(1) to R(5) and R(A), R(B), R(C) and R(D) have the stated meaning, and L is a leaving group which easily undergoes nucleophilic substitution. Compounds I are excellent cardiovascular therapeutic agents.

公开(公告)号：CA2206758C

公开(公告)日：2007-08-14

申请号：CA2206758

申请日：1997-06-04

Applicant: HOECHST AG

Inventor： BRENDEL JOACHIM ,  WEICHERT ANDREAS ,  KLEEMANN HEINZ-WERNER ,  SCHWARK JAN-ROBERT ,  ALBUS UDO ,  LANG HANS JOCHEN ,  SCHOLZ WOLFGANG

IPC: A61K31/165 ,  C07C279/22 ,  A01N1/02 ,  A01N47/44 ,  A61K31/155 ,  A61K31/215 ,  A61K31/275 ,  A61K31/33 ,  A61P3/00 ,  A61P3/06 ,  A61P7/04 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P35/00 ,  C07C319/20 ,  C07C323/44 ,  C07C323/62 ,  C07D207/30 ,  C07D213/60 ,  C07D215/48 ,  C07D217/22 ,  C07D307/34 ,  C07D333/04

Abstract: Ortho-substituted benzoylguanidines of the formula I in which R(1) to R(5) have the meanings given in the claims, are suitable as antiarrhythmic pharmaceuticals having a cardioprotective component for infarct prophylaxis and for infarct treatment and also for the treatment of angina pectoris. They also inhibit in a preventive manner the pathophysiological processes in the formation of ischemically induced damage, in particular in the illicitation of ischemically induced cardiac arrhythmias.