公开(公告)号：LV5745B4

公开(公告)日：1996-12-20

申请号：LV960155

申请日：1996-05-24

Applicant: HOFFMANN LA ROCHE

Inventor： BRANCA QUIRICO ,  JAEUNIN ROLAND ,  MAERKI HANS P ,  MARTI FRAENZI ,  RAMUZ HENRI

IPC: A61K31/415 ,  A61K31/4184 ,  A61K31/425 ,  A61K31/428 ,  A61K31/44 ,  A61K31/55 ,  A61K31/551 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  C07D233/54 ,  C07D233/64 ,  C07D235/14 ,  C07D235/26 ,  C07D243/14 ,  C07D277/62 ,  C07D277/64 ,  C07D401/06 ,  C07D471/04 ,  C07D487/04 ,  C07D521/00

Abstract: Compounds of the formula I wherein R is lower-alkyl, R1 is halogen, R2 is C1-C12-alkyl, R3 is hydroxy, lower-alkoxy, lower-alkyl-carbonyloxy, lower-alkoxy-lower-alkylcarbonoyloxy, lower-alkylaminocarbonyloxy, arylaminocarbonyloxy or aryl-lower alkylaminocarbonyloxy, X is C1-C18-alkylene which optionally can be interrupted by 1,4-phenylene or interrupted or lengthened by 1,4-cyclohexylene, A is di- or tri-substituted 2-imidazolyl attached via an ethylene group or a substituted or unsubstituted heterocycle selected from the group consisting of benzimidazolyl, benzimidazolonyl, imidazo[4,5-c]pyridinyl, imidazo[4,5-c]pyridinonyl, benzthiazolyl, benzodiazepine-2,5-dion-1-yl and pyrrolo[2,1-c]-[1,4]benzodiazepine-5,11-dion-10-yl and n is the number 0 or 1, in the form of racemates and optical antipodes, as well as N-oxides and pharmaceutically usable acid addition salts thereof. The compounds of formual I have a pronounced calcium-antagonistic and anti-arrhythmic activity and can accordingly be used as medicaments, especially for the control or prevention of angina pectoris, ischaemia, arrhythmias, high blood pressure and cardiac insufficiency.

公开(公告)号：BG60937B2

公开(公告)日：1996-06-28

申请号：BG9846994

申请日：1994-02-14

Applicant: HOFFMANN LA ROCHE

Inventor： BRANCA QUIRICO ,  JAUNIN ROLAND ,  MAERKI HANS P ,  MARTI FRAENZI ,  RAMUZ HENRI

IPC: A61K31/415 ,  A61K31/4184 ,  A61K31/425 ,  A61K31/428 ,  A61K31/44 ,  A61K31/55 ,  A61K31/551 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  C07D233/54 ,  C07D233/64 ,  C07D235/14 ,  C07D235/26 ,  C07D243/14 ,  C07D277/62 ,  C07D277/64 ,  C07D401/06 ,  C07D471/04 ,  C07D487/04 ,  C07D521/00

Abstract: Compounds of the formula I wherein R is lower-alkyl, R1 is halogen, R2 is C1-C12-alkyl, R3 is hydroxy, lower-alkoxy, lower-alkyl-carbonyloxy, lower-alkoxy-lower-alkylcarbonoyloxy, lower-alkylaminocarbonyloxy, arylaminocarbonyloxy or aryl-lower alkylaminocarbonyloxy, X is C1-C18-alkylene which optionally can be interrupted by 1,4-phenylene or interrupted or lengthened by 1,4-cyclohexylene, A is di- or tri-substituted 2-imidazolyl attached via an ethylene group or a substituted or unsubstituted heterocycle selected from the group consisting of benzimidazolyl, benzimidazolonyl, imidazo[4,5-c]pyridinyl, imidazo[4,5-c]pyridinonyl, benzthiazolyl, benzodiazepine-2,5-dion-1-yl and pyrrolo[2,1-c]-[1,4]benzodiazepine-5,11-dion-10-yl and n is the number 0 or 1, in the form of racemates and optical antipodes, as well as N-oxides and pharmaceutically usable acid addition salts thereof. The compounds of formual I have a pronounced calcium-antagonistic and anti-arrhythmic activity and can accordingly be used as medicaments, especially for the control or prevention of angina pectoris, ischaemia, arrhythmias, high blood pressure and cardiac insufficiency.

公开(公告)号：AU659832B2

公开(公告)日：1995-06-01

申请号：AU1478892

申请日：1992-04-09

Applicant: HOFFMANN LA ROCHE

Inventor： BRANCA QUIRICO ,  HEITZ MARIE-PAULE ,  NEIDHART WERNER ,  STADLER HEINZ ,  VIERIRA ERIC ,  WOSTL WOLFGANT

IPC: A61K31/16 ,  A61K31/165 ,  A61K31/215 ,  A61K31/22 ,  A61K31/415 ,  A61K31/425 ,  A61K31/426 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/535 ,  A61P9/00 ,  A61P9/04 ,  A61P9/12 ,  C07C317/44 ,  C07C317/50 ,  C07C323/51 ,  C07D207/08 ,  C07D207/12 ,  C07D211/22 ,  C07D213/40 ,  C07D213/53 ,  C07D213/56 ,  C07D231/12 ,  C07D233/54 ,  C07D233/56 ,  C07D233/58 ,  C07D233/60 ,  C07D233/61 ,  C07D233/64 ,  C07D277/20 ,  C07D277/30 ,  C07D295/088 ,  C07D295/185 ,  C07D295/205 ,  C07D307/54 ,  C07D317/24 ,  C07D333/24 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D521/00 ,  C07H15/12 ,  C07K5/06 ,  A61K37/02

Abstract: The compounds of the formula in which A, R , R , R , R and R have the meaning given in Claim 1, in the form of optically pure diastereomers, diastereomer mixtures, diastereomeric racemates or mixtures of diastereomeric racemates and pharmaceutically utilisable salts thereof inhibit the action of the natural enzyme renin and can accordingly be used in the form of pharmaceutical preparations in the control or prevention of high blood pressure and cardiac insufficiency. They can be prepared by various processes known per se.

公开(公告)号：HK110494A

公开(公告)日：1994-10-21

申请号：HK110494

申请日：1994-10-12

Applicant: HOFFMANN LA ROCHE

Inventor： BRANCA QUIRICO ,  JAUNIN ROLAND ,  MAERKI HANS P ,  MARTI FRAENZI ,  RAMUZ HENRI

IPC: A61K31/415 ,  A61K31/4184 ,  A61K31/425 ,  A61K31/428 ,  A61K31/44 ,  A61K31/55 ,  A61K31/551 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  C07D233/54 ,  C07D233/64 ,  C07D235/14 ,  C07D235/26 ,  C07D243/14 ,  C07D277/62 ,  C07D277/64 ,  C07D401/06 ,  C07D471/04 ,  C07D487/04 ,  C07D521/00

Abstract: Compounds of the formula I wherein R is lower-alkyl, R1 is halogen, R2 is C1-C12-alkyl, R3 is hydroxy, lower-alkoxy, lower-alkyl-carbonyloxy, lower-alkoxy-lower-alkylcarbonoyloxy, lower-alkylaminocarbonyloxy, arylaminocarbonyloxy or aryl-lower alkylaminocarbonyloxy, X is C1-C18-alkylene which optionally can be interrupted by 1,4-phenylene or interrupted or lengthened by 1,4-cyclohexylene, A is di- or tri-substituted 2-imidazolyl attached via an ethylene group or a substituted or unsubstituted heterocycle selected from the group consisting of benzimidazolyl, benzimidazolonyl, imidazo[4,5-c]pyridinyl, imidazo[4,5-c]pyridinonyl, benzthiazolyl, benzodiazepine-2,5-dion-1-yl and pyrrolo[2,1-c]-[1,4]benzodiazepine-5,11-dion-10-yl and n is the number 0 or 1, in the form of racemates and optical antipodes, as well as N-oxides and pharmaceutically usable acid addition salts thereof. The compounds of formual I have a pronounced calcium-antagonistic and anti-arrhythmic activity and can accordingly be used as medicaments, especially for the control or prevention of angina pectoris, ischaemia, arrhythmias, high blood pressure and cardiac insufficiency.

公开(公告)号：MX19616A

公开(公告)日：1994-02-28

申请号：MX1961690

申请日：1990-02-22

Applicant: HOFFMANN LA ROCHE

Inventor： BRANCA QUIRICO

IPC: A61K20060101 ,  A61K31/16 ,  C07C20060101 ,  C07C237/22 ,  C07C271/22 ,  C07D213/40 ,  C07D217/06 ,  C07D233/24 ,  C07D263/04 ,  C07D295/20 ,  C07D317/20 ,  C07F7/18 ,  C07K5/02

公开(公告)号：NZ233020A

公开(公告)日：1992-10-28

申请号：NZ23302090

申请日：1990-03-21

Applicant: HOFFMANN LA ROCHE

Inventor： BRANCA QUIRICO ,  MARKI HANS PETER ,  NEIDHART WERNER ,  RAMUZ HENRI ,  WOSTL WOLFGANG

IPC: A61K31/16 ,  A61K31/27 ,  A61K31/38 ,  A61K31/381 ,  A61K31/415 ,  A61K31/425 ,  A61K31/426 ,  A61K31/4427 ,  A61K31/445 ,  A61K38/00 ,  A61K38/55 ,  A61P9/00 ,  A61P9/12 ,  C07C237/06 ,  C07C271/16 ,  C07C271/18 ,  C07C271/20 ,  C07D231/12 ,  C07D233/54 ,  C07D233/64 ,  C07D277/20 ,  C07D277/30 ,  C07D333/24 ,  C07D401/12 ,  C07D403/12 ,  C07K5/02 ,  C07K5/065 ,  C07D413/12 ,  C07K5/06 ,  A61K31/535 ,  A61K37/64

Abstract: The compounds of the formula … … in which A, R , R , R and R have the meaning stated in Claim 1,… in the form of optically pure diastereomers, mixtures of diastereomers, diastereomeric racemates or mixtures of diastereomeric racemates, and pharmaceutically utilisable salts thereof, inhibit the action of the natural enzyme renin and can accordingly be used in the form of pharmaceutical products for controlling or preventing high blood pressure and heart failure. They can be prepared by various processes known per se.

公开(公告)号：FI921718A

公开(公告)日：1992-10-18

申请号：FI921718

申请日：1992-04-16

Applicant: HOFFMANN LA ROCHE

Inventor： BRANCA QUIRICO ,  HEITZ MARIE-PAULE ,  NEIDHART WERNER ,  STADLER HEINZ ,  VIEIRA ERIC ,  WOSTL WOLFGANG

IPC: A61K31/16 ,  A61K31/165 ,  A61K31/215 ,  A61K31/22 ,  A61K31/415 ,  A61K31/425 ,  A61K31/426 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/535 ,  A61P9/00 ,  A61P9/04 ,  A61P9/12 ,  C07C317/44 ,  C07C317/50 ,  C07C323/51 ,  C07D207/08 ,  C07D207/12 ,  C07D211/22 ,  C07D213/40 ,  C07D213/53 ,  C07D213/56 ,  C07D231/12 ,  C07D233/54 ,  C07D233/56 ,  C07D233/58 ,  C07D233/60 ,  C07D233/61 ,  C07D233/64 ,  C07D277/20 ,  C07D277/30 ,  C07D295/088 ,  C07D295/185 ,  C07D295/205 ,  C07D307/54 ,  C07D317/24 ,  C07D333/24 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D521/00 ,  C07H15/12

Abstract: The compounds of the formula in which A, R , R , R , R and R have the meaning given in Claim 1, in the form of optically pure diastereomers, diastereomer mixtures, diastereomeric racemates or mixtures of diastereomeric racemates and pharmaceutically utilisable salts thereof inhibit the action of the natural enzyme renin and can accordingly be used in the form of pharmaceutical preparations in the control or prevention of high blood pressure and cardiac insufficiency. They can be prepared by various processes known per se.

公开(公告)号：UY23402A1

公开(公告)日：1992-10-13

申请号：UY23402

申请日：1992-04-10

Applicant: HOFFMANN LA ROCHE

Inventor： STADLER HEINZ ,  BRANCA QUIRICO ,  HELTZ MARIE-PAULE ,  NELDHART WERNER ,  VIEIRA ERIC ,  WOSTL WOLFGANG

IPC: A61K31/16 ,  A61P9/04 ,  A61K31/165 ,  A61K31/215 ,  A61K31/22 ,  A61K31/415 ,  A61K31/425 ,  A61K31/426 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/535 ,  A61P9/00 ,  A61P9/12 ,  C07C317/44 ,  C07C317/50 ,  C07C323/51 ,  C07D207/08 ,  C07D207/12 ,  C07D211/22 ,  C07D213/00 ,  C07D213/40 ,  C07D213/53 ,  C07D213/56 ,  C07D231/12 ,  C07D233/00 ,  C07D233/54 ,  C07D233/56 ,  C07D233/58 ,  C07D233/60 ,  C07D233/61 ,  C07D233/64 ,  C07D277/00 ,  C07D277/20 ,  C07D277/30 ,  C07D295/088 ,  C07D295/185 ,  C07D295/205 ,  C07D307/54 ,  C07D317/24 ,  C07D333/24 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D521/00 ,  C07H15/12

Abstract: Procedimiento para la preparación de derivados de aminoácido de fórmula general (I) (figura 1), en forma de diastereoisómeros ópticamente puros, mezclas de racematos disteroisómericos, así como sales farmacéuticamente utilizables de estos compuestos, donde: R1 siginifica cicloalquilo, fenilo, fenilo sustituido, naftilo, tienilo, piridilo, quinolilo, isoquinolilo o bencilo; B significa un átomo de azufre o un grupo sulfinilo o sulfonilo. El procedimiento comprende por ejemplo: hacer reaccionar un compuesto de fórmula general (II) (figura 2) donde R31 significa entre otras posibilidades imidazol-1-ilmetilo, imidazol-2-ilmetilo, 2-aminoimidazol-4-ilmetilo, con un ácido de fórmula general (III) (figura 3) o un derivado activado respectivo. Ejemplo no limitante: [(S)-2-[[(S o R)-2-[[(S)-1-[[(1S,2R,3S)-1-(ciclohexilmetil)-3-ciclopropil-2,3-dihidroxipropil]carbamoil]-2-imidazol-4-iletil]carbamoil]-3-fenil-propil[sulfonil]-1-(metoxicarbonil)-2-metilpropil]carbamato de butilo terciario. Los compuestos conforme a la invención tienen actividad de la enzima natural renina y pueden utilizarse en forma de preparados farmacéuticos en el control o prevención de hipertensión e insuficiencia cardiaca.

公开(公告)号：ZA9104808B

公开(公告)日：1992-03-25

申请号：ZA9104808

申请日：1991-06-21

Applicant: HOFFMANN LA ROCHE

Inventor： BRANCA QUIRICO ,  QUIRICO BRANCA ,  MUELLER MARCEL ,  MARCEL MUELLER ,  STADLER HEINZ ,  HEINZ STADLER ,  WOSTL WOLFGANG ,  WOLFGANG WOSTL ,  HEITZ MARIE-PAULE ,  MARIE-PAULE HEITZ ,  NEIDHART WERNER ,  WERNER NEIDHART ,  VIEIRA ERIC ,  ERIC VIEIRA

IPC: A61K31/435 ,  A61K31/495 ,  A61K31/50 ,  A61P9/00 ,  A61P9/12 ,  C07D263/06 ,  C07D471/04 ,  C07D487/04 ,  A61K ,  C07C ,  C07D

CPC classification number: C07D471/04 ,  C07D263/06 ,  C07D487/04

公开(公告)号：IS3725A7

公开(公告)日：1991-12-29

申请号：IS3725

申请日：1991-06-27

Applicant: HOFFMANN LA ROCHE

Inventor： BRANCA QUIRICO ,  MUELLER MARCEL ,  STADLER HEINZ ,  VIEIRA ERIC ,  HEITZ MARIE-PAULE ,  NEIDHART WERNER ,  WOSTL WOLFGANG

IPC: A61K31/435 ,  A61K31/495 ,  A61K31/50 ,  A61P9/00 ,  A61P9/12 ,  C07D263/06 ,  C07D471/04 ,  C07D487/04 ,  C07D ,  C07C ,  A61K