公开(公告)号：JPH10298157A

公开(公告)日：1998-11-10

申请号：JP8558198

申请日：1998-03-31

Applicant: HOECHST AG

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

IPC: A61K31/155 ,  A61K31/165 ,  A61P3/06 ,  A61P9/00 ,  A61P9/06 ,  A61P9/10 ,  A61P11/00 ,  A61P13/02 ,  A61P15/00 ,  A61P25/00 ,  A61P35/00 ,  C07C279/10 ,  C07C279/20 ,  C07C279/22

Abstract: PROBLEM TO BE SOLVED: To produce the subject new compound, capable of manifesting excellent antiarrhythmic properties without causing unfavorable diuretic properties and useful as an antiarrhythymic agent having a cardiac protecting ingredient for preventing and treating infraction and treating angina pectoris. SOLUTION: This compound is represented by formula I [R(1) is CF3 ; either one of R(2) and R(3) is H and the other is C(OH)(CH3 )-CH2 OH, CH(CH3 )-CH2 OH or C(OH)(CH3 )2 ; R(4) is methyl, methoxy, Cl or CF3 ] or its salt, e.g. 4-(1'- hydroxy-2'-propyl)-2-methyl-5-trifluoromethylbenzoylguanidine hydrochloride. The compound represented by formula I is produced by reacting a compound represented by formula II (L is a readily nucleophilically substitutable residue and is methoxy, 1-imidazolyl, etc.) with guanidine.

公开(公告)号：JPH10287641A

公开(公告)日：1998-10-27

申请号：JP4365298

申请日：1998-02-25

Applicant: HOECHST AG

Inventor： BRENDEL JOACHIM ,  LANG HANS JOCHEN DR ,  GERLACH UWE DR

IPC: C07D239/24 ,  A61K31/18 ,  A61K31/335 ,  A61K31/38 ,  A61K31/39 ,  A61K31/495 ,  A61P1/00 ,  A61P9/00 ,  C07C311/07 ,  C07D239/70 ,  C07D313/08 ,  C07D321/02 ,  C07D321/06

Abstract: PROBLEM TO BE SOLVED: To provide a new pharmaceutically active compound giving influence to a potassium channel and IKS channel opening by cyclic adenosine monophosphate and useful for the prevention and treatment of cardiovascular diseases and the treatment of the ulcer of gastrointestinal region, etc. SOLUTION: This compound is expressed by formula I X1 is O, S or CR(1)R(2) [R(1) and R(2) are each H, CF3 , etc.]; X2 is CR(1)R(2), etc.; X3 is CR(1)R(2), etc.; X4 is CR(1)R(2) or NR(6) [R(6) is same as X1]; Y1 to Y4 are each CR(12) [R(12) is H, F, etc.] or N; R(3) is phenyl, etc.; R(4) is Cr H2r -R(20) [the CH2 groups of Cr H2r may be substituted with O, S, etc.; (r) is 0-20; R(20) is H, methyl, etc.]; R(5) is H, etc.}, e.g. 3-fluoro-5-(N-ethylsulfonylamino)-6,7,8,9- tetrahydro-5H-benzocycloheptene. The compound of the formula I can be produced by reacting a compound of formula II with a compound of formula III (M is H, Li, etc.).

公开(公告)号：JPH10182610A

公开(公告)日：1998-07-07

申请号：JP34546997

申请日：1997-12-15

Applicant: HOECHST AG

Inventor： BRENDEL JOACHIM ,  LANG HANS JOCHEN ,  GERLACH UWE ,  WEIDMANN KLAUS

IPC: C07D239/22 ,  A61K31/33 ,  A61K31/35 ,  A61K31/352 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/505 ,  A61K31/535 ,  A61K31/536 ,  A61K31/54 ,  A61K31/545 ,  A61P1/00 ,  A61P1/04 ,  A61P9/00 ,  A61P43/00 ,  C07D207/325 ,  C07D211/14 ,  C07D213/06 ,  C07D213/75 ,  C07D215/42 ,  C07D217/22 ,  C07D239/94 ,  C07D241/04 ,  C07D265/06 ,  C07D265/16 ,  C07D265/20 ,  C07D277/20 ,  C07D295/08 ,  C07D295/12 ,  C07D311/68 ,  C07D311/70 ,  C07D333/10 ,  C07D335/00 ,  C07D417/04

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound useful as a medicine for preventing or treating arrhythmia and further treating ulcer within a region of gastrointestine, or diarrheal disease, etc. SOLUTION: This new compound is a compound of formula I X is O, S, SO, etc.; Y is N, CR11 (R11 is H or a 1-3C alkyl); R1 and R2 are each H, CF3 , F, methoxy, etc.; R3 is a R12-Cn H2n (having CH2 substituted by O, CO, S, SO, etc.) [R12 is H, methyl, CF3 , etc.; (n) is 0-10]; R4 is a R14-Cr H2r (having CH2 substituted by O, CH=CH, etc.) [R14 is methyl, CF3 , etc.; (r) is 0-20], etc.; R5 and R6 form S-CR15=CR16 (R15 and R16 are each H, F, Cl, etc.) by bonding each other, etc.}, e.g. 4-(N-ethylsulfonyl-N-methyl)amino-2-phenylquinazoline. The compound of formula I is obtained, for example, by reacting a compound of formula II with a sulfonic acid derivative of formula III (W is a nucleofuge such as Cl).

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：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：JPH10231293A

公开(公告)日：1998-09-02

申请号：JP3711698

申请日：1998-02-19

Applicant: HOECHST AG

Inventor： LANG HANS JOCHEN DR ,  BRENDEL JOACHIM ,  GERLACH UWE DR ,  WEIDMANN KLAUS DR

IPC: C07D311/60 ,  A61K31/35 ,  A61K31/352 ,  A61P1/00 ,  A61P9/00 ,  C07D311/68 ,  C07D311/70

Abstract: PROBLEM TO BE SOLVED: To obtain the subject new compound consisting of a specific sulfonamide-substituted chromane, exhibiting K channel blocking and gastric- acid secretion inhibiting effects, and useful for, e.g. prevention or treatment of gastric ulcer, enterelcosis, esophagitis regurgitica, diarrhea, allorhythmia and ventricular fibrillation. SOLUTION: This compound is a new chromane derivative shown by formula I R(1) and R(2) are each H, CF3 , C2 F5 , a 1-6C alkyl, (substituted)phenyl or the like; R(A) is O, H, a 1-6C alkanoyloxyl or the like; R(B) is H, forms a bond together with R(A) or the like; R(3) is shown by formula II (R(9) is H or a 3-8C cycloalkyl; (n) is 0 to 10; (m) is 0 or 1; R(11) is H, a 1-6C alkyl or the like; R(4) is an R(12)-Cr H2r [R(12) is H, a 3-8C cycloalkyl, piperidyl, 1- pyrrolidyl or the like]; R(5) to R(8) are each H, a halogen, a 1-6C alkyl, a 3-8C cycloalkyl, CN, CF3 , N3 or the like}, and useful, e.g. as a K channel blocking agent, gastric-acid secretion inhibitor, and for treatment of duodenal ulcer, esophagitis regurgitica, diarrhea, for prevention of treatment of allorhythmia and for prevention of ventricular fibrillation.

公开(公告)号：JPH10218855A

公开(公告)日：1998-08-18

申请号：JP2863598

申请日：1998-02-10

Applicant: HOECHST AG

Inventor： GERLACH UWE DR ,  BRENDEL JOACHIM ,  LANG HANS JOCHEN DR ,  WEIDMANN KLAUS DR

IPC: C07D335/02 ,  A61K31/015 ,  A61K31/18 ,  A61K31/215 ,  A61K31/38 ,  A61K31/382 ,  A61K31/435 ,  A61K31/47 ,  A61P9/00 ,  C07C13/20 ,  C07C311/07 ,  C07C403/04 ,  C07D211/72 ,  C07D215/42 ,  C07D335/06

Abstract: PROBLEM TO BE SOLVED: To obtain the subject new compound useful for treating gastrointestinal ulcer such as duodenal ulcer and treating/preventing arrhythmia through its potent and specific blocking effect on K channel different from K (ATP) channel. SOLUTION: This new compound is expressed by formula I X is S(O)q ((q) is 0-2), etc.; R(1) and R(2) are each H, CF3 , etc.; R(3) is R(12)-Ca H2a [NR(13)]m ; R(12) is H, a 3-8C cycloalkyl, etc.; (a) is 0-10; (m) is 0 or 1; R(13) is H, etc.; R(4) is R(14)-Cr H2r ; (r) is 1-20; R(14) is H, etc.; R(5) and R(6) are each CR(15)=CR(16)-CR(17)-CR(18), etc.; R(15) to R(18) are each H, F, etc.; R(7) is H, etc.; R(8) is H, etc.}, e.g. N-methyl-N-(7-nitro-1,2,3,4- tetrahydronaphthalen-1-yl)-methanesulfonamide. There are various synthetic methods for this compound; one of them being as follows: a compound of formula II (L is a nucleofugic eliminable group) is reacted with a compound of formula III (M is Li, K, etc.) in the presence of a base such as NaOH in a polar organic solvent at -10 to 140 deg.C.

公开(公告)号：CA2206362C

公开(公告)日：2007-11-20

申请号：CA2206362

申请日：1997-05-28

Applicant: HOECHST AG

Inventor： GHATE ANIL VASANTRAO ,  KLEEMANN HEINZ-WERNER ,  ENGLERT HEINRICH CHRISTIAN ,  ALBUS UDO ,  LAL BANSI ,  BRENDEL JOACHIM ,  LANG HANS JOCHEN

IPC: C07C279/22 ,  C07D295/14 ,  A01N1/02 ,  A01N47/44 ,  A61K31/155 ,  A61K31/16 ,  A61K31/165 ,  A61K31/275 ,  A61K31/395 ,  A61K31/445 ,  A61P3/06 ,  A61P9/00 ,  A61P9/06 ,  A61P9/10 ,  C07C271/22 ,  C07C279/20 ,  C07C303/40 ,  C07C311/19 ,  C07C311/47 ,  C07C315/04 ,  C07C317/32 ,  C07C317/50 ,  C07C319/20 ,  C07C323/44 ,  C07C323/62 ,  C07D207/30 ,  C07D295/155

Abstract: Substituted 1-naphthoylguanidines, process for their preparation, their use as a medicament or diagnostic, and medicament containing them. Substituted 1-naphthoylguanidines of the formula I see formula I in which R2 to R8 have the meanings indicated in the claims, are suitable as antiarrhythmic pharmaceuticals having a cardioprotective component for infarct prophylaxis and infarct treatment and for the treatment of angina pectoris. They also preventively inhibit the pathophysiological processes in the formation of ischemically induced damage, in particular in the production of ischemically induced cardiac arrhythmias.

公开(公告)号：CA2213714C

公开(公告)日：2007-08-14

申请号：CA2213714

申请日：1997-08-22

Applicant: HOECHST AG

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

IPC: C07C279/22 ,  C07D213/65 ,  A01N1/00 ,  A61K31/155 ,  A61K31/16 ,  A61K31/165 ,  A61K31/275 ,  A61K31/34 ,  A61K31/38 ,  A61K31/395 ,  A61K31/44 ,  A61K31/4406 ,  A61P3/06 ,  A61P9/00 ,  A61P9/06 ,  A61P9/10 ,  A61P13/02 ,  A61P15/00 ,  A61P25/00 ,  A61P43/00 ,  C07C277/08 ,  C07C279/20 ,  C07C311/47 ,  C07C317/32 ,  C07C323/62 ,  C07D207/36 ,  C07D295/15 ,  C07D295/26 ,  C07D307/58 ,  C07D333/32

Abstract: Compounds of the formula I (see formula I) where T is (see formula II) and R(A), R(B), R(C), R(D), R(E), R(F), x and y have the meanings indicated in the claims, and their pharmaceutically acceptable salts are effective inhibitors of the cellular sodium-proton antiporter (Na+/H+ -exchanger). They are therefore outstandingly suitable for treatment of all illnesses which are to be attributed to increased Na+/H+ exchange.

公开(公告)号：CA2197628C

公开(公告)日：2006-05-16

申请号：CA2197628

申请日：1997-02-14

Applicant: HOECHST AG

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

IPC: C07D333/24 ,  C07D333/30 ,  A61K31/38 ,  A61K31/381 ,  A61K31/395 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P35/00 ,  A61P43/00 ,  C07C279/22 ,  C07D333/02 ,  C07D333/06 ,  C07D333/34

Abstract: Substituted thiophenylalkenylcarboxylic acid guanidides, processes for the ir preparation, their use as a medicament or diagnostic, and a medicament containing them. There are described substituted thiophenylalkenylcarboxylic acid guanidides of the formula I in which R(1) to R(5) have the meanings given in the claims, which are outstandingly active antiarrhythmic pharmaceuticals having a cardioprotectiv e component and are outstandingly suitable for infarct prophylaxis and infarct treatment and also for the treatment of angina pectoris, where they also inhibit or greatly reduce the pathophysiological processes in the formation of ischemically induced damage, in particular in the initiation of ischemically induced cardiac arrhythmias, in a preventive manner.