公开(公告)号：JPH1067782A

公开(公告)日：1998-03-10

申请号：JP18958997

申请日：1997-07-15

Applicant: HOFFMANN LA ROCHE

Inventor： DIEDERICH FRANCOIS ,  OBST ULRIKE ,  WEBER LUTZ

IPC: A61K31/00 ,  A61K31/40 ,  A61K31/407 ,  A61P7/00 ,  A61P7/02 ,  A61P9/00 ,  A61P9/08 ,  A61P9/10 ,  A61P29/00 ,  A61P35/00 ,  C07D487/00 ,  C07D487/02 ,  C07D487/04 ,  C07D487/14

Abstract: PROBLEM TO BE SOLVED: To obtain an oxopyrrolopyrrole derivative comprising a specific oxopyrrolopyrrole derivative and useful as a medicine for preventing and treating a decease caused by thrombin-induced platelet aggregation or thrombin- induced aggregation of fibrinogen in blood plasma. SOLUTION: This oxopyrrolopyrrole derivative is the new one (a hydrate or a salt) of formula I [R is a lower alkyl, a cycloalkyl or phenyl; R is H, OH or a group of the formula C(O)O-A (A is a lower alkyl, a cycloalkyl or phenyl); R to R are each methyl, or R is H, and R and R form trimethylene by bonding each other] and useful as a medicine, etc., for preventing and treating a decease caused by thrombin-induced platelet aggregation or thrombin- induced aggregation of fibrinogen in blood plasma. The compound is obtained by reacting a bromo derivative of formula II with CuCN in DMF by heating to form a nitrile of formula III, reacting the nitrile with HCl in methanol and thereafter reacting the resultant product with ammonia.

公开(公告)号：WO2004048335A3

公开(公告)日：2004-08-19

申请号：PCT/EP0313087

申请日：2003-11-21

Applicant: HOFFMANN LA ROCHE

Inventor： BANNER DAVID WILLIAM ,  GOBBI LUCA CLAUDIO ,  GROEBKE ZBINDEN KATRIN ,  OBST ULRIKE ,  STAHL CHRISTOPH MARTIN

IPC: A61K31/155 ,  C07C243/38 ,  C07C257/18 ,  C07C259/18 ,  C07C271/66 ,  C07D211/46 ,  C07D213/30 ,  C07D213/38 ,  C07D213/56 ,  C07D213/65 ,  C07D213/73 ,  C07D239/42 ,  C07D265/36 ,  C07D271/06 ,  C07D295/14 ,  C07D295/15 ,  C07D309/12 ,  C07D311/04 ,  C07D521/00

CPC classification number: C07C257/18 ,  C07C259/18 ,  C07D211/46 ,  C07D213/30 ,  C07D213/38 ,  C07D213/56 ,  C07D213/65 ,  C07D213/73 ,  C07D231/12 ,  C07D233/56 ,  C07D239/42 ,  C07D249/08 ,  C07D265/36 ,  C07D271/06 ,  C07D295/15 ,  C07D309/12 ,  C07D311/04

Abstract: The invention is concerned with novel mandelic acid derivatives of formula (I), wherein R to R , X and Y are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit the formation of coagulation factors Xa, IXa and thrombin induced by factor VIIa and tissue factor and can be used as medicaments.

Abstract translation: 本发明涉及式（I）的新型扁桃酸衍生物，其中R 1至R 10，X和Y如说明书和权利要求书中所定义，以及其生理学上可接受的盐。 这些化合物抑制由因子VIIa和组织因子诱导的凝血因子Xa，IXa和凝血酶的形成，并且可以用作药物。

公开(公告)号：YU83602A

公开(公告)日：2006-05-25

申请号：YUP83602

申请日：2001-05-17

Applicant: HOFFMANN LA ROCHE

Inventor： ALIG LEO ,  GROEBKE ZBINDEN KATRIN ,  HILPERT KURT ,  KUEHNE HOLGER ,  OBST ULRIKE ,  WESSEL HANS PETER

IPC: A61K31/155 ,  A61K31/198 ,  A61K31/216 ,  A61K31/341 ,  A61P7/02 ,  A61P7/04 ,  A61P9/00 ,  A61P9/10 ,  A61P29/00 ,  A61P35/00 ,  C07C257/18 ,  C07C257/20 ,  C07C259/18 ,  C07C269/00 ,  C07C271/64 ,  C07C273/18 ,  C07C275/56 ,  C07D307/20 ,  C07D317/36

Abstract: Pronalazak se odnosi na nove N-(4-karbamimidoil-fenil)-glicin derivate formule (I), naznačene time što X i R1 do R5 imaju značenje dato u opisu i zahtevima pronalaska, kao i na vodene rastvore i rastvore i/ili na njihove fiziološki prihvatljive soli i/ili na njihove fiziološki prihvatljive estre.[The invention is concerned with novel N-(4-carbamimidoyl-phenyl)-glycine derivatives of the formula (I) wherein X and R1 to R5 are as defined in the description and in the claims, as well as hydrates or solvates and/or physiologically acceptable salts thereof and/or physiologically acceptable esters thereof.

公开(公告)号：BR0316508A

公开(公告)日：2005-10-04

申请号：BR0316508

申请日：2003-11-21

Applicant: HOFFMANN LA ROCHE

Inventor： BANNER DAVID WILLIAM ,  GOBBI LUCA CLAUDIO ,  ZBINDEN KATRIN GROEBKE ,  OBST ULRIKE ,  STAHL CHRISTOPH MARTIN

IPC: A61K31/155 ,  C07C243/38 ,  C07C257/18 ,  C07C259/18 ,  C07C271/66 ,  C07D211/46 ,  C07D213/30 ,  C07D213/38 ,  C07D213/56 ,  C07D213/65 ,  C07D213/73 ,  C07D239/42 ,  C07D265/36 ,  C07D271/06 ,  C07D295/14 ,  C07D295/15 ,  C07D309/12 ,  C07D311/04 ,  C07D521/00 ,  C07D213/00

Abstract: The invention is concerned with novel mandelic acid derivatives of formula (I) wherein R 1 to R 10 , X and Y are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds inhibit the formation of coagulation factors Xa, IXa and thrombin induced by factor VIIa and tissue factor.

公开(公告)号：NO20052311A

公开(公告)日：2005-06-16

申请号：NO20052311

申请日：2005-05-11

Applicant: HOFFMANN LA ROCHE

Inventor： BANNER DAVID WILLIAM ,  ZBINDEN KATRIN GROEBKE ,  STAHL CHRISTOPHE MARTIN ,  GOBBI LUCA CLAUDIO ,  OBST ULRIKE

IPC: A61K31/155 ,  C07C243/38 ,  C07C257/18 ,  C07C259/18 ,  C07C271/66 ,  C07D211/46 ,  C07D213/30 ,  C07D213/38 ,  C07D213/56 ,  C07D213/65 ,  C07D213/73 ,  C07D239/42 ,  C07D265/36 ,  C07D271/06 ,  C07D295/14 ,  C07D295/15 ,  C07D309/12 ,  C07D311/04 ,  C07D521/00

CPC classification number: C07C257/18 ,  C07C259/18 ,  C07D211/46 ,  C07D213/30 ,  C07D213/38 ,  C07D213/56 ,  C07D213/65 ,  C07D213/73 ,  C07D231/12 ,  C07D233/56 ,  C07D239/42 ,  C07D249/08 ,  C07D265/36 ,  C07D271/06 ,  C07D295/15 ,  C07D309/12 ,  C07D311/04

公开(公告)号：AR042109A1

公开(公告)日：2005-06-08

申请号：ARP030104302

申请日：2003-11-21

Applicant: HOFFMANN LA ROCHE

Inventor： STAHL CHRISTOPH MARTIN ,  BANNER DAVID WILLIAM ,  GOBBI LUCA CLAUDIO ,  GROEBKE ZBINDEN KATRIN ,  OBST ULRIKE

IPC: A61K31/155 ,  C07C243/38 ,  C07C257/18 ,  C07C259/18 ,  C07C271/66 ,  C07D211/46 ,  C07D213/30 ,  C07D213/38 ,  C07D213/56 ,  C07D213/65 ,  C07D213/73 ,  C07D239/42 ,  C07D265/36 ,  C07D271/06 ,  C07D295/14 ,  C07D295/15 ,  C07D309/12 ,  C07D311/04 ,  C07D521/00 ,  C07D213/13 ,  C07D213/31 ,  C07D213/46 ,  C07D213/52 ,  C07D213/61 ,  C07D215/12 ,  C07D217/12 ,  C07D317/64 ,  C07D317/66 ,  C07D491/056 ,  C07D491/052 ,  C07D498/04 ,  C07C233/11 ,  A61K31/161 ,  A61K31/36 ,  A61K31/4245 ,  A61K31/436 ,  A61K31/4375 ,  A61K31/44 ,  A61K31/47 ,  A61K31/5375 ,  A61K31/538 ,  A61K31/5383 ,  A61P7/00 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  A61P35/00

Abstract: La presente se refiere a derivados de ácido mandélico de la fórmula (1), así como a las sales fisiológicamente aceptables de los mismos. Estos compuestos inhiben la formación de los factores de coagulación Xa, IXa y trombina inducida por el factor VIIa y el factor hístico y pueden utilizarse como medicamentos. Reivindicación 1: Compuestos de la fórmula (1) en la que R1 es H, -OH, -NH2, (alcoxi inferior)-carbonilo, aril-(alcoxi inferior)-carbonilo, ariloxi-carbonilo, (alquilo inferior)-carbonilo, aril-carbonilo o (alcoxi inferior)-carbonilo que está sustituido por halógeno; R2, R3, y R4 con independencia entre sí se eligen entre H, halógeno, hidroxi, y alcoxi inferior; cuyo alcoxi inferior puede estar sustituido opcionalmente por hidroxi, carboxi o carbamoilo; R5 es alquilo inferior o cicloalquilo o, si X es O o NR12, R5 puede ser también H; R6 es H, alquilo inferior o flúor-alquilo inferior; Y es N o C-R11; R7, R8, R9, R10 y R11 con independencia entre sí se eligen entre H, hidroxi, halógeno, amino, (alquilo inferior)-amino, di-(alquilo inferior)-amino, (alquilo inferior)-carbonil-amino, NO2, flúor-alquilo inferior, alcoxi inferior, hidroxi-alcoxi inferior, flúor-alcoxi inferior, alquinilo inferior, hidroxi-alquinilo inferior, arilo, aril-alcoxi inferior, ariloxi, ariloxi-alcoxi inferior, heterociclilo, heterocicliloxi, (alcoxi inferior)-carbonil-alcoxi inferior, carbamoil-alcoxi inferior, carboxi-alcoxi inferior, cicloalquiloxi, heteroarilo, amino-alcoxi inferior, (alquilo inferior)-amino-alcoxi inferior y di-(alquilo inferior)-amino-alcoxi inferior; o R8 y R9 o R8 y R7 están unidos entre sí para formar un anillo junto con los átomos de C a los que están unidos y R8 y R9 juntos o R8 y R7 juntos son -O-CH2-O-, -O-CH2-CO-NH-, -O-CH2-CH2-CH2- o -CH=CH-CH=CH-, que pueden estar eventualmente sustituidos por alquilo inferior o alcoxi inferior y R10, R11 y R7 o R9 tienen respectivamente los significados definidos anteriormente; X es O, S, NR12 o SO2; R12 es H, alquilo inferior o (alquilo inferior)-carbonilo; y las sales farmacéuticamente aceptables de los mismos. Reivindicación 37: El uso de los compuestos según una cualquiera de las reivindicaciones 1-26 para la fabricación de medicamentos destinados al tratamiento terapéutico y/o profiláctico de trombosis arteriales y venosas, trombosis de venas profundas, embolia pulmonar, angina de pecho inestable, infarto cardíaco, apoplejía debida a fibrilación atrial, inflamación, arteriosclerosis y/o tumores.

公开(公告)号：JO2241B1

公开(公告)日：2004-10-07

申请号：JOP20030011

申请日：2003-02-02

Applicant: HOFFMANN LA ROCHE

Inventor： OBST ULRIKE ,  LEO ALIG ,  KATRIN GROEBKE ZBINDEN

IPC: A61K31/445 ,  A61K31/4465 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  A61P29/00 ,  A61P35/00 ,  C07D211/22 ,  C07D211/42 ,  C07D211/46

Abstract: The Invention is concerned with novel water soluble N-(4-carbamimidoyl-phenyl)-glycine derivatives of formula (I) Wherein R1 to R4 and n are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These Compounds inhibit the formation of coagulation factors Xa, IXa and thrombin included by factor Vlla and tissue factor and can be used as medicaments.

公开(公告)号：PA8589201A1

公开(公告)日：2004-07-26

申请号：PA8589201

申请日：2003-11-20

Applicant: HOFFMANN LA ROCHE

Inventor： OBST ULRIKE ,  STHAL CHRISTOPH MARTIN ,  GOBBI LUCA CLAUDIO ,  ZBINDEN KATRIN GROEBKE ,  BANNER DAVID WILLIAM

IPC: A61K31/155 ,  C07C243/38 ,  C07C257/18 ,  C07C259/18 ,  C07C271/66 ,  C07D211/46 ,  C07D213/30 ,  C07D213/38 ,  C07D213/56 ,  C07D213/58 ,  C07D213/65 ,  C07D213/73 ,  C07D239/42 ,  C07D265/36 ,  C07D271/06 ,  C07D295/14 ,  C07D295/15 ,  C07D309/12 ,  C07D311/04 ,  C07D521/00 ,  C07D259/18

Abstract: LA INVENCION SE REFIERE A NUEVOS DERIVADOS DE ACIDO MANDELICO DE LA FORMULA (I) EN LA QUE DE R1 A R10, X Y Y TIENEN LOS SIGNIFICADOS DEFINIDOS EN LA DESCRIPCION Y EN LAS REIVINDICACIONES, ASI COMO A LAS SALES FISIOLOGICAMENTE ACEPTABLES DE LOS MISMOS. ESTOS COMPUESTOS INHIBEN LA FORMACION DE LOS FACTORES DE COAGULACION XA, IXA Y TROMBINA INDUCIDA POR EL FACTOR VIIA Y EL FACTOR HISTICO Y PUEDEN UTILIZARSE COMO MEDICAMENTOS.

公开(公告)号：ZA200208899B

公开(公告)日：2004-02-19

申请号：ZA200208899

申请日：2002-11-01

Applicant: HOFFMANN LA ROCHE

Inventor： ALIG LEO ,  HILPERT KURT ,  OBST ULRIKE ,  ZBINDEN KATRIN GROEBKE ,  KUEHNE HOLGER ,  WESSEL HANS PETER

IPC: A61K31/155 ,  A61K31/198 ,  A61K31/216 ,  A61K31/341 ,  A61P7/02 ,  A61P7/04 ,  A61P9/00 ,  A61P9/10 ,  A61P29/00 ,  A61P35/00 ,  C07C257/18 ,  C07C257/20 ,  C07C259/18 ,  C07C269/00 ,  C07C271/64 ,  C07C273/18 ,  C07C275/56 ,  C07D307/20 ,  C07D317/36 ,  C07C ,  C07D ,  A61K ,  A61P

Abstract: N-(4-carbamimidoyl-phenyl)-glycine derivatives have the formula:wherein X and R1 to R5 are as defined herein, and includes hydrates or solvates and/or physiologically acceptable salts thereof and/or physiologically acceptable esters thereof.

公开(公告)号：DE59610771D1

公开(公告)日：2003-11-20

申请号：DE59610771

申请日：1996-02-19

Applicant: HOFFMANN LA ROCHE

Inventor： DIEDERICH FRANCOIS ,  OBST ULRIKE ,  WALLBAUM SABINE ,  WEBER LUTZ

IPC: A61K31/40 ,  A61P7/02 ,  A61P9/00 ,  A61P9/08 ,  A61P9/10 ,  A61P29/00 ,  A61P35/00 ,  C07D471/14 ,  C07D487/04 ,  C07D487/14 ,  C07D513/14 ,  A61K31/425

Abstract: Octahydro-1,3-dioxo-pyrrolo(3,4-c)pyrrole derivs. of formula (I), and hydrates, solvates and salts of (I), are new. R1, R2 = T (opt. substd. by Ar, Het, Cy, CONH2 or COOT), H, Ar, Het or Cy; or R2 may also be lower alkanoyl; R3 = H, COOH, CONH2, COOT, CONHT or CONT2; R4-R6 = H, T, Ar, aralkyl or Cy; or R4 and/or one of R5 and R6 is Het or T (substd. by OH, SO2H, SO3H, guanidino, aryl-lower alkyloxy, TO or TS); or R2+R4 = a tri- or tetramethylene gp. in which (a) one of the methylene gps. is opt. replaced by S, SO or SO2, or opt. substd. by OH, T, lower alkenyl or COOT, or (b) one of the methylene gps. is opt. substd. by lower alkenyl and another is opt. substd. by lower alkyl-COOH; at least one of R1-R6 is a gp. substd. by amino, amidino, guanidino or N-hydroxyamidino; T = lower alkyl; Ar = aryl; Het = heteroaryl; Cy = cycloalkyl.