公开(公告)号：JPH1081664A

公开(公告)日：1998-03-31

申请号：JP13822797

申请日：1997-05-28

Applicant: HOECHST AG

Inventor： BRENDEL JOACHIM DR ,  KLEEMANN HEINZ-WERNER DR ,  ENGLERT HEINRICH CHRISTIAN DR ,  LANG HANS JOCHEN DR ,  SCHWARK JAN-ROBERT DR ,  WEICHERT ANDREAS DR ,  LAL BANSI

IPC: C07D295/14 ,  A01N1/02 ,  A01N47/44 ,  A61K31/155 ,  A61K31/165 ,  A61K31/27 ,  A61K31/44 ,  A61K31/495 ,  A61K31/535 ,  A61K31/5375 ,  A61P3/06 ,  A61P9/00 ,  A61P9/06 ,  A61P9/10 ,  A61P35/00 ,  A61P43/00 ,  C07C271/22 ,  C07C277/08 ,  C07C279/20 ,  C07C279/22 ,  C07C311/19 ,  C07C317/50 ,  C07C323/62 ,  C07D213/40 ,  C07D213/75 ,  C07D295/08 ,  C07D295/088

Abstract: PROBLEM TO BE SOLVED: To obtain the subject new pharmaceutical compound useful for the prevention and treatment of infarction, the treatment of stenocardia, etc., as an antiarrhythmic agent containing a heart-protecting component. SOLUTION: The objective compound is expressed by the formula I [at least one of R1 and R3 to R8 is XYa WZ or X'Ya WZ' (X is O, S, etc.; Y is an alkylene having 1-8 CH2 groups; W is CH2 , SO2 , etc.; Z is C(=O)R(15), etc.; R(15) is N=C(NH2 )2 ; (a) is 0 or 1; X' is C=O, SO, etc.; Z' is C(=O)R(15), etc.], e.g. 6-(2-diethylaminoethoxy)-2-naphthoylguanidine dihydrochloride. The compound of the formula I can be produced by reacting a compound of the formula II (L is an eliminable group which may have a nucleophilic substituent) with guanidine. The compound of the formula I is useful for the treatment and prophylaxis of ischemia-induced arrhythmia, CNS ischemia, shock diseases, hypertension, prostatic hyperplacia, prostomegaly, etc.

公开(公告)号：JPH1081663A

公开(公告)日：1998-03-31

申请号：JP13822697

申请日：1997-05-28

Applicant: HOECHST AG

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

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

Abstract: PROBLEM TO BE SOLVED: To obtain the subject new pharmaceutical compound useful for the prevention and treatment of infarction, the treatment of stenocardia, etc., as an antiarrhythmic agent containing a heart-protecting component. SOLUTION: The objective compound is expressed by the formula I [R2 to R8 are each H, F, Cl, Br, I, CN, NO2 , CF3 , C2 F5 or Xa Yb Z (X is O, S, C=O, etc.; Y is an alkylene having 1-8 CH2 groups; Z is H, a 1-7C alkyl, etc.; (a) is 0 or 1; (b) is 0 or 1)] or its salt, e.g. 4-fluoro-1-naphthoylguanidine hydrochloride. The compound of the formula I can be produced by reacting a compound of the formula II (L is an eliminable group which may have a nucleophilic substituent) with guanidine. The compound of the formula I is useful for the treatment and prophylayis of ischemia-induced arrhythmia, cardiac infarction, stenocardia, etc., treatment of shock diseases, surgical operation and organ transplantation, the treatment for prostatic hyperplacia, etc. It is useful also as a diagnostic agent for hypertension, atherosclerosis, diabetes, proliferative diseases, etc.

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：JPH10109970A

公开(公告)日：1998-04-28

申请号：JP22461397

申请日：1997-08-21

Applicant: HOECHST AG

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

IPC: C07D213/65 ,  A01N1/00 ,  A61K31/155 ,  A61K31/165 ,  A61K31/44 ,  A61K31/4406 ,  A61P3/06 ,  A61P9/00 ,  A61P9/06 ,  A61P9/10 ,  A61P13/02 ,  A61P15/00 ,  A61P25/00 ,  A61P43/00 ,  C07C277/08 ,  C07C279/20 ,  C07C279/22

Abstract: PROBLEM TO BE SOLVED: To produce phenyl-substituted alkenylcarboxylic guanizid, which is a selective inhibitor of sodium/proton exchanger and can be used for treatment of arrhythmia, myocardial infarction, angina petoris, etc. SOLUTION: This phenyl-substituted alkenylcarboxylic guanizid of formula I [T is formula II [R(A) is H, a halogen, CN, etc.; R(B), R(C), and R(D) are each R(A); (x) and (y) are each 0-2; R(F) is H, a halogen, CN, etc.; R(E) is R(FF)], R(1) is T, H, a halogen, etc.; R(2)-R(5) are each R(1) or -CH-CH=CH- CH- in their combination, F, Cl, CF3 , etc.], for example, 1,2-bis(3-E-2- methylpropenic guanizid)]benzene dichloride, is obtained by a reaction of a compound of formula III (L is a nucleophilically replaceable eliminatory group with ganidine. This phenyl-substituted alkenylcarboxylic guanizid is effective for ischemic condition of heart, peripheral and central nerves, peripheral organs and extremities, shocks, etc.

公开(公告)号：JPH1081662A

公开(公告)日：1998-03-31

申请号：JP13622397

申请日：1997-05-27

Applicant: HOECHST AG

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

IPC: A61K31/165 ,  A61K31/155 ,  A61P3/06 ,  A61P9/00 ,  A61P9/10 ,  C07C277/06 ,  C07C279/22 ,  C07C311/15 ,  C07C317/44 ,  C07C323/62

Abstract: PROBLEM TO BE SOLVED: To obtain the subject new pharmaceutical compound useful for the prevention and treatment of infarction, the treatment of stenocardia, etc., as an antiarrhythmic agent containing a heart-protecting component. SOLUTION: The objective compound is expressed by the formula I [R(1) to R(3) are each R(10)-SOa , etc., (R(10) is a 1-8C alkyl, etc.; (a) is 0-2); R(4) and R(5) are each a 1-4C alkyl, a 1-4C alkoxy, OH, etc.], e.g. 2,6- dichlorobenzoylguanidine hydrochlorice. The compound of the formula I can be produced by reacting a compound of the formula II (L is an eliminable group which may have nucleophilic substituent) with guanidine and optionally converting the product into a salt. The compound of the formula I is useful for the treatment and prophylayis of diseases caused by ischemic state, treatment of shock diseases, surgical operation and organ transplantation, the treatment for prostatic hyperplacia, etc. It is useful also as a diagnostic agent for hypertension, atherosclerosis, diabetes, proliferative diseases, etc.

公开(公告)号：JPH10204064A

公开(公告)日：1998-08-04

申请号：JP2255898

申请日：1998-01-21

Applicant: HOECHST AG

Inventor： KLEEMANN HEINZ-WERNER DR ,  LANG HANS JOCHEN DR ,  SCHWARK JAN-ROBERT DR ,  WEICHERT ANDREAS DR ,  FABER SABINE DR ,  JANSEN HANS-WILLI DR

IPC: C07D233/60 ,  A01N1/02 ,  A61K31/415 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P11/00 ,  A61P43/00 ,  C07D233/54 ,  C07D233/61 ,  C07D233/64 ,  C07D233/66 ,  C07D233/68 ,  C07D233/70 ,  C07D233/84 ,  C07D233/90

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound useful for producing a medicine for treatment or prophylaxis of diseases induced by ischemica symptom or for producing a medicine for treatment of disturbed respiration. SOLUTION: This compound is represented by formula I [R1 is H, a 1-8C alkyl or a Ca H2a -phenyl [(a) is 0, 1 or 2]; R2 and R3 are each 1-8C alkyl, a 3-7C cycloalkyl or Cg H2g -phenyl [(g) is 0, 1 or 2]; R4 and R5 are each H, a 1-8C alkyl, F, Cl, etc.], e.g. ethyl-2-butyl-5-methylsulfanyl-3-(2'- cyanoaminosulfonylbiphenyl-4-ylmethyl)-3Hθimidazole-4-carboxylate, etc. Furthermore, the compound of formula I is preferably obtained by reacting, e.g. a compound of formula II with an auxiliary strong base such as K2 SO3 in a dipolar aprotic solvent such as acetonitrile at 0 deg.C to a boiling point of used solvent.

公开(公告)号：JPH1067733A

公开(公告)日：1998-03-10

申请号：JP15938297

申请日：1997-06-17

Applicant: HOECHST AG

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

IPC: A61K31/165 ,  A01N1/02 ,  A01N47/44 ,  A61K31/10 ,  A61K31/155 ,  A61K31/18 ,  A61P3/06 ,  A61P3/10 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P35/00 ,  A61P43/00 ,  C07C279/10 ,  C07C279/20 ,  C07C279/22 ,  C07C303/40 ,  C07C311/19 ,  C07C311/47 ,  C07C317/42 ,  C07C317/50

Abstract: PROBLEM TO BE SOLVED: To obtain a new benzoylguanidine and its pharmaceutically permissible salt useful for cardiac infarction, arrhythmia, angina and shock states caused by ischemic states, and further useful in the fields of surgical operations, organ grafts, etc. SOLUTION: A benzoylguanidine of formula I [R(1) is R(13) -SOm , R(14) R(15) N-SO2 [(m) is 1, 2; R(13) is an alkyl, a perfluoroalkyl, an alkenyl, etc.; R(14) is H, an alkyl, a perfluoroalkyl, an alkenyl, etc.; R(15) is H, an alkyl, a perfluoroalkyl; R(14) and R(15) together form a methylene group]; one of R(2) and R(3) is H, and the other is CHR(30) R(31) [R(30) is a group of the formula II [R(32) is H, methyl; (q)-(i) are each 0-4; (k) is 1-4]; R(31) is H, an alkyl], etc.; R(4) is an alkyl, etc.,} or its salt, e.g. 2-chloro-3-(1'-hydroxy-2'-propyl'-5- methylsulfonylbenzoylguanidine. The compound of formula I is obtained by reacting a compound of formula III (L is a releasable group) with guanidine.

公开(公告)号：JPH1067731A

公开(公告)日：1998-03-10

申请号：JP14439397

申请日：1997-06-03

Applicant: HOECHST AG

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

IPC: A61K31/165 ,  A01N1/02 ,  A01N47/44 ,  A61K31/155 ,  A61P3/00 ,  A61P3/06 ,  A61P7/04 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P35/00 ,  C07C279/22 ,  C07C319/20 ,  C07C323/62

Abstract: PROBLEM TO BE SOLVED: To obtain a new ortho-substituted benzoylguanidine or its pharmaceutically permissible salt useful as a medicine for treating and preventing cardiac infarction, arrhythmia, stenocardia, etc., caused by ischemic states. SOLUTION: An ortho-substituted benzoylguanidine of formula I [R(1) is H, F, Cl, Br, an alkyl, an alkoxy, a cycloalkyl, a cyclalkoxy, etc., or phenyl, naphthyl, biphenyl, a heteroaryl, or C[R(15) R(16) ]OH, etc., (R(15) , R(16) are each H, an alkyl, etc.); one of R(2) , R(3) is always R(1) ; R(4) , R(5) are each H, an alkyl, an alkoxy, F, Cl, Br, etc.,] or its salt, e.g. 4-acetyloxy-2-chloro-5- trifluoromethylbenzoylguanidine hydrochloride salt. The compound of formula I is obtained by reacting a compound of formula II (L is a releasable group capable of being easily nucleophilically substituted) with guanidine. The compound of formula I is active for antitheroselerotic arteriosclerosis, cancers, etc.

公开(公告)号：EP0814077A1

公开(公告)日：1997-12-29

申请号：EP97109546

申请日：1997-06-12

Applicant: HOECHST AG

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

IPC: A61K31/165 ,  A01N1/02 ,  A01N47/44 ,  A61K31/10 ,  A61K31/155 ,  A61K31/18 ,  A61P3/06 ,  A61P3/10 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P35/00 ,  A61P43/00 ,  C07C279/10 ,  C07C279/20 ,  C07C279/22 ,  C07C303/40 ,  C07C311/19 ,  C07C311/47 ,  C07C317/42 ,  C07C317/50

CPC classification number: A61K31/155 ,  Y10S514/821 ,  Y10S514/825

Abstract: Benzoylguanidine der Formel I worin bedeuten: R(1)R(13)-SOm oder R(14)R(15)N-SO2-; m1 oder 2; einer der Substituenten (R2) und R(3) Wasserstoff; und der jeweils andere Substituent R(2) und R(3) -CHR(30)R(31); R(30) -(CH2)g-(CHOH)h-(CH2)i-(CHOH)k-R(32) oder -(CH2)g-O-(CH2-CH2O)h-R(24); -C(OH)R(33)R(34); und R(4), R(13), R(14), R(15), R(24), R(31), R(32), g, h, i und k, die in den Ansprüchen gegebenen Bedeutungen haben, sind wertvolle antiarrhythmische Arzneimittel mit cardioprotektiver Komponente, auch zur Prävention ischämisch induzierter Schäden, insbesondere bei der Auslösung ischämisch induzierter Herzarrhythmien. Sie werden infolge Inhibition des zellulären Na /H -Austauschmechanismus zur Behandlung akuter oder chronischer durch Ischämie ausgelöster Schäden verwendet werden. Darüber hinaus zeichnen sie sich durch starke inhibierende Wirkung auf die Proliferationen von Zellen aus. Sie sind zur Verhinderung der Genese des Bluthochdrucks geeignet. Außerdem erniedrigen sie erhöhte Serum Konzentrationen an LDL und VLDL.

Abstract translation: 式（I）的Benzoylguanidines化合物及其盐是新的。 R1 = R13-SOM或R14R15N-SO 2; M = 1或2; R13 = 1-8C烷基或全氟烷基，3-8C烯基或为CnH2n-R16; N = 0-4; R16 = 3-8C环烷基或苯基，联苯基或萘基（其各自任选被1-3个氟，氯，CF 3，CH 3，OCH 3或NR 25 R 26取代）; R25，R26 = H或1-4C的烷基或全氟烷基; R14 = H，1-8C烷基或全氟烷基，3-8C烯基或为CnH2n-R27; R27 = 3-8C环烷基或苯基，联苯基或萘基（其各自任选被1-3个氟，氯，CF 3，CH 3，OCH 3或NR28R29取代的）; R28，R29，R15 = H，或1-4C-烷基或全氟烷基; 或R14 + R15 =（CH 2）a，其中一个CH 2基团可以被O，S，NH，N-CH 3或N-苄基取代; 一个= 4-5; R2，R3 = H，而另一个= CHR30R31或C（OH）R33R34中的一个; R30 =（CH 2）G-（CHOH）H-（CH 2）I-（CHOH）K-R32或 - （CH 2）G-O-（CH2-CH2O）H-R24; R24，R32 = H或Me; G，H，I = 0-4; K = 1-4; R31，R33，R34 = H或1-4C烷基; 或R33 + R34 = 3-6C环烷基; 或R33 = CH 2 OH; R4 = 1-4C烷基或烷氧基或氟，氯，溴，I，CN，（CH 2）N“ - （CF 2）O-CF 3; N“= 0-1; 和o = 0-2。

公开(公告)号：EP0794171A3

公开(公告)日：1998-08-19

申请号：EP97102606

申请日：1997-02-19

Applicant: HOECHST AG

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

IPC: A61K31/165 ,  A01N1/02 ,  A61K31/155 ,  A61P9/00 ,  A61P9/08 ,  A61P9/10 ,  A61P35/00 ,  A61P43/00 ,  C07C279/22

CPC classification number: C07C279/22

Abstract: Ortho-substituierte Benzoylguanidine der Formel I worin R(1) bis R(4) die in den Ansprüchen angegebenen Bedeutungen haben, sind als antiarrhythmische Arzneimittel mit cardioprotektiver Komponente zur Infarktprophylaxe und der Infarktbehandlung sowie zur Behandlung der angina pectoris geeignet.
Sie inhibieren auch präventiv die pathophysiologischen Vorgänge beim Entstehen ischämisch induzierter Schäden, insbesondere bei der Auslösung ischämisch induzierter Herzarrhythmien.