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：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：JPH1129545A

公开(公告)日：1999-02-02

申请号：JP20275697

申请日：1997-07-29

Applicant: HOECHST AG

Inventor： GUPTE RAVINDRA DATTATRAYA ,  WEICHERT ANDREAS ,  SCHWARK JAN-ROBERT ,  GHATE ANIL VASANTRAO ,  VADLAMUDI RAO VENKATA SATYA VE ,  RAMAKRISHNA NIROGI VENKATA SAT ,  JAIN ARUN KUMAR ,  LAL BANSI

IPC: A61K31/155 ,  A01N1/00 ,  A61K31/00 ,  A61K31/165 ,  A61P3/06 ,  A61P9/00 ,  A61P9/06 ,  A61P9/10 ,  A61P9/12 ,  A61P25/00 ,  A61P43/00 ,  C07C279/22 ,  C07C327/50 ,  C07C327/54

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound used for medicines for treating or preventing arrhythmia, cardiac infarction, angina pectoris, ischemic state of heart, ischemic state of peripheral or central nervous system, ischemic state of peripheral organs and four limbs, shock state, etc. SOLUTION: This compound is represented by formula I [R1 to R6 , are each or together H, an (O-)1-10C alkyl, F, a (substituted)aryl or the like; X is O, S or NH; R7 to R10 are each or together a (cyclo)alkyl, an (alkyl)aryl or R8 and R9 together form a part of 5-, 6- or 7 membered heterocycle], e.g. 4 methyl-1-indanylidineacetylguanidine-methanesulfonic acid. The compound of formula I is obtained by reacting a compound of formula II [Y is a leaving group selected from O-1-4C alkyl, a halogen and imidazolyl] with a guanidine of formula III and, as necessary, converting the resultant compound to its salt.

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：JPH107644A

公开(公告)日：1998-01-13

申请号：JP4747997

申请日：1997-03-03

Applicant: HOECHST AG

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

IPC: A61K31/165 ,  A01N1/02 ,  A61K31/155 ,  A61P3/10 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  A61P13/08 ,  A61P25/00 ,  A61P35/00 ,  A61P43/00 ,  C07C279/10 ,  C07C279/20 ,  C07C279/22

Abstract: PROBLEM TO BE SOLVED: To obtain the subject new compound showing high activity against Na /H exchange inhibition, improved in water solubility, excellent in antiarrhythmic properties in consequence, useful for preventing and treating infarctions and treating angina pectoris as an antiarryhythmic medicine. SOLUTION: This compound is shown by formula I [R(1) is H, F, Cl, Br, I, CN, NO2 , a 1-8C alkyl, etc.; one of R(2) and R(3) is hydroxyl and the other is as shown for R(1); R(4) is a 1-4C alkyl, a 1-4C alkoxy, F, Cl, Br, etc.] or its pharmaceutically permissible salt such as 2,6-dichlorobenzoylguanidine hydrochloride. The compound of formula I is synthesized by reacting a compound of formula II (L is an eliminable group which may be subjected to nucleophilic substitution) with guanidine.

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：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.