公开(公告)号：ID17038A

公开(公告)日：1997-12-04

申请号：ID971869

申请日：1997-06-02

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: Ortho-substituted benzoyl-guanidines of formula (I) and their salts are new: R = H; F; Cl; Br; I; CN; NO2; 1-8 C alkyl; 1-8 C alkoxy; 3-8 C cycloalkyl; 3-8 C cycloalkoxy; Xa-(CH2)b-(CF2)c-CF3; SR ; OR ; CR R R ; Ph, etc.;R or R = OCOR and the other = R ;R , R = H; 1-4C alkyl; 1-4C alkoxy; etc.;X = e.g. O; a = 0 or 1;b = 0-2;c = 0-3;R = -CfH2f-Q;Q = e.g. 3-8 C cycloalkyl;f = 0-2; R , R = H; 1-4 C alkyl; or R ; R = e.g. 1-8C alkyl.

公开(公告)号：DE19608161A1

公开(公告)日：1997-09-11

申请号：DE19608161

申请日：1996-03-04

Applicant: HOECHST AG

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

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 ,  C07C277/08 ,  C07D215/02 ,  C07D217/02 ,  C07D213/04

Abstract: Ortho-substituted benzoyl-guanidines of formula (I) and their salts are new: where R1 = H, F, Cl, Br, I, CN, NO2, 1-8C alkyl, 1-8C alkoxy, 3-8C cycloalkyl, 3-8C cycloalkoxy, Xa-(CH2)b-(CF2)c-CF3, SR10, OR10, CR10R11R12; or phenyl, naphthyl, biphenylyl, or 1-9C (sic) heteroaryl bonded via C or N and all optionally mono- to tri-substituted with F, Cl, CF3, CH3, methoxy, OH, NH2, NHCH3, NH(CH3)2; or SR13, OR13, NHR13, NR13R14, CHR13R15, CR15R16-OH, C IDENTICAL CR18, CR19=CHR18, ÄCR20R21Ük-CO, ÄCR22R23Ül-R24; one of R2, R3 = hydroxy the other as R1; R4 = 1-4C alkyl, 1-4C alkoxy, F, Cl, Br, I or (CH2)n-(CF2)o-CF3; X = O, S, NR5; a = 0-1; b = 0-2; c = 0-3; R5 = H, 1-4C alkyl, CdH2d-R6; d = 0-4; R6 = 3-8C cycloalkyl; or phenyl, biphenylyl or naphthyl (each optionally mono- to tri-substituted with F, Cl, CF3, methyl, methoxy, or NR7R8); R7, R8 = H or 1-4C alkyl; R10 = CfH2f-3-8C cycloalkyl; or phenyl optionally mono- to tri-substituted with F, Cl, CF3, CH3, methoxy, OH, NH2, NHCH3, NH(CH3)2; f = 0-2; R11, R12 = as R10, H or 1-4C alkyl; k = 0-4; l = 0-4; R13, R14 = (CH2)g-(CHOH)h-(CH2)i-(CHOH)j-R17, or (CH2)g-O-(CH2CH2O)h-R24; R17 = H, CH3; g, h, i = 0-4; j = 1-4; R15, R16 = H or 1-6C alkyl; or CR15R16 = 3-8C cycloalkyl; R18 = phenyl optionally mono- to tri-substituted with F, Cl, CF3, CH3, OCH3 or NR25R26; or 3-8C cycloalkyl; or 1-9C (sic) heteroaryl optionally substituted as for phenyl; or 1-6C alkyl optionally substituted by 1-3 OH; R25, R26 = H or 1-4C alkyl; R19-R23 = H or CH3; R24 = H, 1-6C alkyl, 3-8C cycloalkyl, CmH2m-R18; m = 1-4; n = 0-1; and o = 0-1.

公开(公告)号：ID16042A

公开(公告)日：1997-08-28

申请号：ID970554

申请日：1997-02-24

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 ,  A61P1/16 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P13/02 ,  A61P15/00 ,  A61P35/00 ,  A61P43/00 ,  C07C279/10 ,  C07C279/20 ,  C07C279/22 ,  C07C279/02

Abstract: Ortho-substituted benzoylguanidines of formula (I) and their salts are new: R2, R3 = H, Cl, Br, I, 1-8C alkyl, 3-8C cycloalkyl or OR5; provided that one, but not both of R2 or R3 = H; R5 = 1-8C alkyl, or CdH2d-(3-8C cycloalkyl); and d = 0-2.

公开(公告)号：DE19540995A1

公开(公告)日：1997-05-07

申请号：DE19540995

申请日：1995-11-03

Applicant: HOECHST AG

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

IPC: A61K31/165 ,  A61K31/18 ,  A61P1/16 ,  A61P3/08 ,  A61P9/04 ,  A61P9/08 ,  A61P9/10 ,  A61P11/00 ,  A61P13/02 ,  A61P15/00 ,  A61P35/00 ,  A61P41/00 ,  A61P43/00 ,  C07C279/18 ,  C07C313/02 ,  C07C313/06 ,  C07C381/10 ,  C07C311/21 ,  C07C311/15 ,  C07C303/40 ,  C07C317/48 ,  A61K49/00

Abstract: Sulphonimidamides of formula R1N=S(O)(R2)N(R4)(R3) (I) and their salts are new: at least one of R1-R3 = a benzoylguanidine group of formula (a) optionally substituted in the phenyl ring by 1-4 of 1-8C alkyl, 2-8C alkenyl, (CH2)mR14, halo, CN, CF3, R22SO2, R23R24NCO, R25CO, R26R27NSO2, OR35, SR35 or NR35R36; m = 0-2; R14 = 3-8C cycloalkyl, phenyl optionally substituted by 1-3 of F, Cl, CF3, Me, OMe or NR15R16; R15, R16 = H or Me; R22, R23, R25, R26 = 1-8C alkyl, 2-8C alkenyl, (CH2)nR29 or CF3; or R23+R24, R26+R27 = 5-6 methylene groups with optionally one CH2 replaced by O, S, NH, NMe or N-benzyl; or R23, R25, R26 = H; n = 0-4; R29 = 3-7C cycloalkyl, phenyl optionally substituted by 1-3 of F, Cl, CF3, Me, OMe or NR30R31; R30, R31 = H or 1-4C alkyl; R24, R27 = H or 1-4C alkyl; R35, R36 = H or 1-6C alkyl; or R35+R36 = 4-7 methylene groups with optionally one CH2 replaced by O, S, NH, NMe or N-benzyl; or R35 = phenyl optionally substituted by 1-3 of F, Cl, CF3, Me, OMe, SO2R5, SO2NR6R7 or NR32R33; R5 = 1-6C alkyl; R6, R7 = H or 1-4C alkyl; R32, R33 = H or 1-4C alkyl; or R35 = 1-9C heteroaryl optionally substituted by 1-3 of F, Cl, CF3, CH3, OMe, OH, NH2, NHMe or N(Me)2; the remaining R1-R3 = 1-8C alkyl or (CH2)pR10; or the remaining R1, R2 = H; p = 0-4; R10 = phenyl optionally substituted by 1-3 of F, Cl, CF3, Me, OMe, SO2NR17R8 or SO2R9; R17, R8 = H or 1-4C alkyl; R9 = 1-4C alkyl; and R4 = H or 1-4C alkyl.

公开(公告)号：GR3022136T3

公开(公告)日：1997-03-31

申请号：GR960403574

申请日：1996-12-20

Applicant: HOECHST AG

Inventor： LANG HANS-JOCHEN DR ,  KLEEMANN HEINZ-WERNER DR ,  SCHOLZ WOLFGANG DR ,  ALBUS UDO DR

IPC: A61K31/165 ,  A61K31/415 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/4412 ,  A61K31/47 ,  A61K31/472 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  C07C279/22 ,  C07C311/08 ,  C07C317/44 ,  C07C323/62 ,  C07D207/32 ,  C07D213/64 ,  C07D213/643 ,  C07D213/65 ,  C07D213/66 ,  C07D213/68 ,  C07D213/70 ,  C07D215/20 ,  C07D215/26 ,  C07D217/02 ,  C07D217/24 ,  C07D233/54 ,  C07D249/08 ,  C07D521/00

公开(公告)号：DE19526381A1

公开(公告)日：1997-01-23

申请号：DE19526381

申请日：1995-07-19

Applicant: HOECHST AG

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

IPC: A61K49/00 ,  A01N1/02 ,  A61K31/155 ,  A61K31/165 ,  A61K31/18 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P41/00 ,  C07C303/40 ,  C07C311/16 ,  C07C315/04 ,  C07C317/44

Abstract: Benzoyl-guanidine derivs. of formula (I) and their salts are new: R1 = R4-SOm, R5R6N-SO2-, -Op-(CH2)q-(CF2)r-CF3, -SR10, -OR10 or -CR10R11R12; m = 1-2; R4, R5 = 1-8C alkyl, 3-6C alkenyl, CF3 or -CnH2n-R7; n = 0-4; R6 = H or 1-4C alkyl; R7 = 3-8C cycloalkyl or Ph (opt. substd. with 1-3 substits. from F, Cl, CF3, Me, OMe and NR8R9; R8, R9 = H or 1-4C alkyl; R5 = H; or R5 + R6 = 4-5C methylene group (with opt. replacement of a CH2 by O, S, NH, NMe or N-benzyl; ; p = 0-1; q = 0-2; r = 0-3;R10, R11, R12 = H, 1-8C alkyl, CsH2s-(3-8C cycloalkyl) or an aromatic gp. chosen from pyridyl, pyrrolyl, quinolyl, isoquinolyl, imidazolyl or Ph (in which the aromatic system may be opt. 1-3 times substd. by F, Cl, CF3, Me, OMe, OH, NH2, NHMe or N(Me)2; s = 0-2; R2 = -(CH2)u-(CF2)t-CF3; t = 0-3; u = 0-1; R3 = H or as for R1.

公开(公告)号：ES2092729T3

公开(公告)日：1996-12-01

申请号：ES93110195

申请日：1993-06-25

Applicant: HOECHST AG

Inventor： WEICHERT ANDREAS DR ,  LANG HANS-JOCHEN ,  SCHOLZ WOLFGANG DR ,  ALBUS UDO DR ,  LANG FLORIAN PROF DR

IPC: A61K31/155 ,  A61K31/18 ,  A61K31/33 ,  A61K31/435 ,  A61K31/44 ,  A61P1/16 ,  A61P3/08 ,  A61P3/10 ,  A61P9/00 ,  A61P9/02 ,  A61P9/06 ,  A61P9/10 ,  A61P11/00 ,  A61P15/04 ,  A61P43/00 ,  C07C277/08 ,  C07C279/22 ,  C07C311/37 ,  C07C315/04 ,  C07C317/32 ,  C07C317/44 ,  C07C323/60 ,  C07D213/56

Abstract: Benzoylguanidines of the formula I with R(1) equal to R(4)-SOm or R(5)R(6)N-SO2- with R(4) and R(5) equal to alk(en)yl, -CnH2n-R(7), and with R(7) equal to cycloalkyl or phenyl, where R(5) can also mean H, R(6) equals H or C1-C4-alkyl, R(2) is hydrogen, (cyclo)alk(en)(yn)yl, aryl and hetaryl R(3) is defined as R(2), and their pharmaceutically tolerated salts, are described. Compounds I are obtained by reacting compounds of the formula II with guanidine, in which L is a leaving group which can easily undergo nuclophilic substitution. Compounds I are outstandingly suitable as antiarrhythmic drugs with cardioprotective component for the treatment and prophylaxis of infarct and for treating angina pectoris, and they also greatly reduce preventively the pathophysiological processes in the development of ischaemia-induced damage. Furthermore, I are distinguished by a potent inhibitory action on cell proliferation. They can thus be used as antiatherosclerotics, remedies for the late complications of diabetes, cancers, fibrotic disorders such as pulmonary, hepatic or renal fibrosis. They are effective inhibitors of the cellular sodium-proton antiporter (Na /H exchanger).

公开(公告)号：DE59304166D1

公开(公告)日：1996-11-21

申请号：DE59304166

申请日：1993-06-25

Applicant: HOECHST AG

Inventor： WEICHERT ANDREAS DR ,  LANG HANS-JOCHEN ,  SCHOLZ WOLFGANG DR ,  ALBUS UDO DR ,  LANG FLORIAN PROF DR

IPC: A61K31/155 ,  A61K31/18 ,  A61K31/33 ,  A61K31/435 ,  A61K31/44 ,  A61P1/16 ,  A61P3/08 ,  A61P3/10 ,  A61P9/00 ,  A61P9/02 ,  A61P9/06 ,  A61P9/10 ,  A61P11/00 ,  A61P15/04 ,  A61P43/00 ,  C07C277/08 ,  C07C279/22 ,  C07C311/37 ,  C07C315/04 ,  C07C317/32 ,  C07C317/44 ,  C07C323/60 ,  C07D213/56

Abstract: Benzoylguanidines of the formula I with R(1) equal to R(4)-SOm or R(5)R(6)N-SO2- with R(4) and R(5) equal to alk(en)yl, -CnH2n-R(7), and with R(7) equal to cycloalkyl or phenyl, where R(5) can also mean H, R(6) equals H or C1-C4-alkyl, R(2) is hydrogen, (cyclo)alk(en)(yn)yl, aryl and hetaryl R(3) is defined as R(2), and their pharmaceutically tolerated salts, are described. Compounds I are obtained by reacting compounds of the formula II with guanidine, in which L is a leaving group which can easily undergo nuclophilic substitution. Compounds I are outstandingly suitable as antiarrhythmic drugs with cardioprotective component for the treatment and prophylaxis of infarct and for treating angina pectoris, and they also greatly reduce preventively the pathophysiological processes in the development of ischaemia-induced damage. Furthermore, I are distinguished by a potent inhibitory action on cell proliferation. They can thus be used as antiatherosclerotics, remedies for the late complications of diabetes, cancers, fibrotic disorders such as pulmonary, hepatic or renal fibrosis. They are effective inhibitors of the cellular sodium-proton antiporter (Na /H exchanger).

公开(公告)号：CZ26596A3

公开(公告)日：1996-08-14

申请号：CZ26596

申请日：1996-01-29

Applicant: HOECHST AG

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

IPC: C07D295/12 ,  A61K31/155 ,  A61K31/18 ,  A61K31/395 ,  A61K31/40 ,  A61K31/415 ,  A61K31/4166 ,  A61K31/4184 ,  A61K31/47 ,  A61K31/495 ,  A61K31/496 ,  A61K31/535 ,  A61K31/5355 ,  A61K31/5375 ,  A61P1/16 ,  A61P3/10 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P13/08 ,  A61P13/12 ,  A61P35/00 ,  C07C279/22 ,  C07C311/15 ,  C07C311/18 ,  C07C311/29 ,  C07C311/64 ,  C07C317/28 ,  C07C317/46 ,  C07C323/16 ,  C07C323/25 ,  C07C335/32 ,  C07C381/10 ,  C07D207/09 ,  C07D213/40 ,  C07D213/70 ,  C07D215/36 ,  C07D233/42 ,  C07D233/54 ,  C07D233/60 ,  C07D233/84 ,  C07D235/28 ,  C07D295/22 ,  C07D521/00 ,  C07C319/20 ,  C07C315/04 ,  C07C277/08 ,  A01N1/02

Abstract: Basic substd. benzoylguanidine derivs. of formula (I) and their salts are new. One of R1-R3 = Xf-CdH2d-B-A-R6 and the others of R1-R3 = H, F, Cl, Br, I, CN, 1-8C alkyl, 2-8C alkenyl, NR35R36 or Zh-CgH2g-R17; R6 = NR7R8, C(=NR9)NR7R8, NR10-C(=NR9)NR7R8 or basic heteroaromatic ring system with 1-9C; R7-R10 = H or 1-4C alkyl; or R7+R8 = C4H8 or CaH2a (opt. with one CH2 replaced by O, S(O)m or NR11; or R8+R9+R10 or R7+R10 = C2H4 or CcH2c (opt. with one CH2 replaced by O, S(O)m or NR11); A = CbH2b (opt. with one or two CH2 replaced by O, CO, CH(OR20), S(O)m, NR20, CONR20, NHCONR20, SO2NHCONR20, S(=O)(=NR19)NR20 or SO2NR20, or one CH2 replaced by CHR99); R7+R99 form pyrrolidine or piperidine; B = opt. substd. phenylene or naphthylene gp. of formula (i) or (ii); R12, R13 = H, Me, F, Cl, Br, I, CF3 or S(O)mR14; R14, R19 = H or 1-4C alkyl; X = O, CO, CH(OR21), SOm or NR21; R35, R36 = H or 1-6C alkyl; or R35+R36 = (CH2)4-7, with one CH2 opt. replaced by S, NH, NMe or N-benzyl; Z = O, CO, SOm, NR18, CONR18, NHCONR18 or SO2NR18; R17 = H, cyclopropyl, cyclopentyl, cyclohexyl, 1-3C perfluoroalkyl, 1-, 2- or 3-pyrrolyl (opt. substd. by 1-4 of F, Cl, Br, I, CN, 2-8C alkanoyl, 2-8C alkoxycarbonyl, CHO, COOH, CF3, Me and OMe) or 3-8C cycloalkyl or phenyl (both opt. substd. by 1-3 of F, Cl, CF3, Me, OH, OMe, NR37R38, SO2Me and SO2NH2); R11, R18, R20, R21, R37, R38 = H or Me; R4, R5 = H, 1-4C alkyl, F, Cl, OR32, NR33R34 or 1-4C perfluoroalkyl; R32-R34 = H or 1-3C alkyl; a = 5-7; b = 1-10; c = 3-5; d = 0-5; g = 0-4; f, h = 0 or 1; m = 0-2.

公开(公告)号：DE4432105A1

公开(公告)日：1996-03-14

申请号：DE4432105

申请日：1994-09-09

Applicant: HOECHST AG

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

IPC: A61K31/165 ,  A61K31/155 ,  A61K31/18 ,  A61K31/275 ,  A61P3/08 ,  A61P3/10 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  A61P13/02 ,  A61P15/00 ,  A61P25/00 ,  A61P25/02 ,  A61P35/00 ,  A61P41/00 ,  A61P43/00 ,  C07C22/00 ,  C07C277/08 ,  C07C279/22 ,  C07C311/29 ,  C07C311/38 ,  C07C317/44 ,  C07C323/62 ,  C07C317/46 ,  C07C315/04 ,  C07C303/36 ,  A01N1/02 ,  C07D213/44 ,  C07D215/12 ,  C07D217/12

Abstract: Benzoylguanidines of formula (I) and their salts are new. R1 and R3 = H, halogen, CN, NO2, 1-8C alkyl, 3-8C cycloalkyl, Oa(CH2)b(CF2)cCF3, S(O)mR5, SO2NR6R7, SR11, OR11, CR11R12R13 or phenyl, naphthyl, biphenylyl or C- or N-bonded 1-9C heteroaryl gps. opt. substd. by 1-3 of F, Cl, CF3, Me, OMe, OH, NH2, NHMe and NMe2; a = 0 or 1; b = 0-2; c = 0-3; m = 0-2; R5 = 1-8C alkyl, 3-6C alkenyl, CF3 or CnH2n-R8; R6 = H, or as for R5; R7 = H or 1-4C alkyl; or R6+R7 = tetra- or pentamethylene, opt. with a CH2 gp. replaced by O, S, NH, NMe or NCH2Ph; n = 0-4; R8 = 3-7C cycloalkyl, or phenyl opt. substd. by 1-3 of F, Cl, CF3, Me, OMe and NR9R10; R9 and R10 = H or 1-4C alkyl; R11 = 3-8C cycloalkyl; (3-8C)cycloalkyl(1-2C)alkyl; or 1-9C heteroaryl or phenyl opt. substd. by 1-3 of F, Cl, CF3, OMe, OH, NH2, NHMe and NMe2; R12 and R13 = H, 1-4C alkyl or gps. as defined for R11; R2 = CF2R14, CF(R15)(R16), CF(Rf)-R15 or CRf=C(R15)(R16); R14 = 1-4C alkyl or 3-6C cycloalkyl; R15 and R16 = H or 1-4C alkyl; Rf = 1-3C perfluoro-n-alkyl; R4 = H, 1-3C alkyl, F, Cl, Br, I, CN or (CH2)s(CF2)tCF3; s = 0 or 1; t = 0-2.