公开(公告)号：JPH09227562A

公开(公告)日：1997-09-02

申请号：JP3616796

申请日：1996-02-23

Applicant: KOWA CO

Inventor： KYOTANI YOSHINORI ,  SHIMIZU NOBORU ,  SATO SEIICHI ,  YAMAGUCHI TAKASHI ,  KITAMURA TAKAHIRO ,  OGIYA TADAAKI ,  KAWAMINE KATSUMI

IPC: C07D491/048 ,  A61K31/40 ,  A61P9/00 ,  B01J23/44 ,  C07B61/00

Abstract: PROBLEM TO BE SOLVED: To obtain an indole derivative useful e.g. as pharmaceuticals having a cardiopathy curative action under mild reaction condition in high yield in a mass by the catalytic reduction of a specific benzylamine compound in the presence of a palladium-carbon catalyst. SOLUTION: The compound of formula III can be produced by reacting 2,3-dihydro-4-hydroxy-5-(1,2-dimethyl-2-propenyl)-3,3,7-trimethyl-1H-i ndol-2-one of formula I with a halogenation agent in an alcohol or a hydrated alcohol solvent in the presence of a base and reacting the resulting halogenated compound of formula II (X is a halogen) with benzylamine. The objective indole derivative having cardiopathy curative action and expressed by formula IV can be produced in a mass in high yield by the catalytic reduction of the benzylamine compound of formula III in the presence of a palladium-carbon catalyst.

公开(公告)号：JPH07173162A

公开(公告)日：1995-07-11

申请号：JP25203594

申请日：1994-10-18

Applicant: KOWA CO

Inventor： KYOTANI YOSHINORI ,  KAWAMINE KATSUMI ,  TAIMA TSUTOMU ,  OGIYA TADAAKI ,  YAMAGUCHI TAKASHI ,  ONOKI KAZUHIRO ,  SATO SEIICHI ,  SHIMIZU NOBORU ,  SHIGYO HIROMICHI ,  OTA TOMIO ,  ODA TOSHIAKI ,  OKUNO YUKIHIRO ,  SHIBUYA MASAYUKI ,  TAKAHASHI YOSHIO ,  FUJII MIKIO ,  UCHIDA YASUYOSHI

IPC: C07D491/048 ,  A61K31/40 ,  A61P9/00 ,  A61P9/04 ,  A61P9/06 ,  A61P9/08

Abstract: PURPOSE:To obtain a new indole derivative having positively inotropic action on cardiac muscle, antiarrhythmic action and vasodilating action and useful as an agent for the treatment of heart diseases such as cardiac insufficiency and arrhythmia. CONSTITUTION:This indole derivative is expressed by formula I (one of R to R is a lower alkyl or a lower alkenyl and the others each is H or a lower alkyl; R and R each is H, a halogen, etc.; R is H, benzyl, etc.; R and R each is H, OH, etc.; A is group of formula II, III, etc.) or its salt, e.g. 2-(1- imidazolylmethyl)-2,3, 7,8-tetrahydro-5,8,8-trimethyl-6H-furo[2,3-e]indol-7-one. The compound can be produced e.g. by reacting an indole compound of formula IV with an allyl halide of formula V (X is a halogen), heating the obtained compound of formula VI to effect the Claisen rearrangement reaction and reacting the product with a halogenating agent such as N-bromosuccinimide.

公开(公告)号：DE69830600T2

公开(公告)日：2006-05-04

申请号：DE69830600

申请日：1998-03-25

Applicant: KOWA CO

Inventor： SHIBUYA KIMIYUKI ,  KAWAMINE KATSUMI ,  SATO YUKIHIRO ,  EDANO TOSHIYUKI ,  HIRATA MITSUTERU ,  OZAKI CHIYOKA

IPC: C07D233/84 ,  A61K31/415 ,  A61K31/42 ,  A61K31/695 ,  C07D235/28 ,  C07D263/58 ,  C07D263/60 ,  C07D277/70 ,  C07D277/74 ,  C07D413/04 ,  C07D413/12 ,  C07D471/04 ,  C07D498/04 ,  C07D513/04 ,  C07F7/10

公开(公告)号：DE69828276T2

公开(公告)日：2005-12-15

申请号：DE69828276

申请日：1998-05-26

Applicant: KOWA CO

Inventor： SHIBUYA K ,  KAWAMINE KATSUMI ,  SATO YUKIHIRO ,  MIURA TORU ,  OZAKI CHIYOKA ,  EDANO TOSHIYUKI ,  HIRATA MITSUTERU

IPC: C07D413/12 ,  A61K31/496 ,  A61K31/506 ,  A61K31/55 ,  A61K31/5513 ,  A61P3/06 ,  A61P9/00 ,  A61P9/10 ,  C07D233/70 ,  C07D235/28 ,  C07D263/58 ,  C07D277/74 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D498/04 ,  C07D513/04 ,  C07F9/6509 ,  C07F9/6558 ,  A61K31/495 ,  C07D277/80 ,  C07D413/04

公开(公告)号：DE69830600D1

公开(公告)日：2005-07-21

申请号：DE69830600

申请日：1998-03-25

Applicant: KOWA CO

Inventor： SHIBUYA KIMIYUKI ,  KAWAMINE KATSUMI ,  SATO YUKIHIRO ,  EDANO TOSHIYUKI ,  HIRATA MITSUTERU ,  OZAKI CHIYOKA

IPC: C07D233/84 ,  C07D235/28 ,  C07D263/58 ,  C07D263/60 ,  C07D277/74 ,  C07D413/04 ,  C07D413/12 ,  C07D471/04 ,  C07D498/04 ,  A61K31/415 ,  A61K31/42 ,  A61K31/695 ,  C07D277/70 ,  C07D513/04 ,  C07F7/10

公开(公告)号：ES2235328T3

公开(公告)日：2005-07-01

申请号：ES98921809

申请日：1998-05-26

Applicant: KOWA CO

Inventor： SHIBUYA K ,  KAWAMINE KATSUMI ,  SATO YUKIHIRO ,  MIURA TORU ,  OZAKI CHIYOKA ,  EDANO TOSHIYUKI

IPC: C07D413/12 ,  A61K31/496 ,  A61K31/506 ,  A61K31/55 ,  A61K31/5513 ,  A61P3/06 ,  A61P9/00 ,  A61P9/10 ,  C07D233/70 ,  C07D235/28 ,  C07D263/58 ,  C07D277/74 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D498/04 ,  C07D513/04 ,  C07F9/6509 ,  C07F9/6558 ,  A61K31/495 ,  A61K31/505 ,  C07D277/80 ,  C07D413/04

Abstract: La presente invención se refiere a nuevos compuestos de diamina cíclicos y a una composición farmacéutica que lo contiene. La presente invención se refiere a un compuesto representado por la fórmula (I) o su(s) sal(es) o solvato(s). (en la fórmula, A es un residuo divalente sustituido de benceno, piridina, ciclohexano o naftaleno o es un grupo vinileno, donde AR es un grupo arilo sustituido X es -NH-, un átomo de oxígeno o un átomo de azufre; Y es -NH1-, un átomo de oxígeno o un átomo de azufre, sulfóxido o sulfona. Z es un enlace sencillo o -NR2-; R1 es átomo de hidrógeno, un grupo alquilo inferior opcionalmente sustituido, un grupo arilo opcionalmente sustituido o un grupo silil alquilo inferior opcionalmente sustituido; l es un número entero de 0 a 15; m es un número entero de 2 ó 3; n es un número entero de 0 a 3). El compuesto de la presente invención es útil como composición farmacéutica, particularmente como inhibidor de aciltransferasa de colesterol A de coenzima de acilo (ACAT)

公开(公告)号：PT987254E

公开(公告)日：2005-04-29

申请号：PT98921809

申请日：1998-05-26

Applicant: KOWA CO

Inventor： KAWAMINE KATSUMI ,  HIRATA MITSUTERU ,  SHIBUYA K ,  YUKIHIRO SATO ,  TORU MIURA ,  CHIYOKA OZAKI ,  TOSHIYUKI EDANO

IPC: C07D413/12 ,  A61K31/496 ,  A61K31/506 ,  A61K31/55 ,  A61K31/5513 ,  A61P3/06 ,  A61P9/00 ,  A61P9/10 ,  C07D233/70 ,  C07D235/28 ,  C07D263/58 ,  C07D277/74 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D498/04 ,  C07D513/04 ,  C07F9/6509 ,  C07F9/6558 ,  A61K31/495 ,  A61K31/505 ,  C07D277/80 ,  C07D413/04

公开(公告)号：CA2290744A1

公开(公告)日：1998-12-03

申请号：CA2290744

申请日：1998-05-26

Applicant: KOWA CO

Inventor： OZAKI CHIYOKA ,  SHIBUYA KIMIYUKI ,  EDANO TOSHIYUKI ,  KAWAMINE KATSUMI ,  SATO YUKIHIRO ,  MIURA TORU ,  HIRATA MITSUTERU

IPC: C07D413/12 ,  A61K31/496 ,  A61K31/506 ,  A61K31/55 ,  A61K31/5513 ,  A61P3/06 ,  A61P9/00 ,  A61P9/10 ,  C07D233/70 ,  C07D235/28 ,  C07D263/58 ,  C07D277/74 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D498/04 ,  C07D513/04 ,  C07F9/6509 ,  C07F9/6558 ,  A61K31/495 ,  A61K31/505 ,  C07D277/80 ,  C07D413/04 ,  C07F9/653

Abstract: Compounds represented by formula (I) and salts or solvates of these, each being useful especially as an acyl coenzyme A cholesterol acyltransferase (ACAT) inhibitor, wherein (a) represents an optionally substituted divalent residue of benzene, pyridine, cyclohexane or naphthalene, or vinylene; Ar represents optionally substituted aryl; X represents -NH-, oxygen, or sulfur; Y represents -NR1-, oxygen, sulfur, sulfoxide, or sulfone; Z represents a single bond or -NR2-; R1 and R2 each represents hydrogen, optionally substituted lower alkyl, optionally substituted aryl, or optionally substituted lower silylalkyl; l is an integer of 0 to 15; m is 2 or 3; and n is an integer of 0 to 3.

公开(公告)号：AU6517698A

公开(公告)日：1998-10-20

申请号：AU6517698

申请日：1998-03-25

Applicant: KOWA CO

Inventor： SHIBUYA KIMIYUKI ,  KAWAMINE KATSUMI ,  SATO YUKIHIRO ,  EDANO TOSHIYUKI ,  HIRATA MITSUTERU ,  OZAKI CHIYOKA

IPC: C07D233/84 ,  C07D235/28 ,  C07D263/58 ,  C07D263/60 ,  C07D277/74 ,  C07D413/04 ,  C07D413/12 ,  C07D471/04 ,  C07D498/04 ,  A61K31/415 ,  A61K31/42 ,  A61K31/425 ,  A61K31/435 ,  C07D277/70 ,  C07D513/04

公开(公告)号：EP0987254A4

公开(公告)日：2000-09-13

申请号：EP98921809

申请日：1998-05-26

Applicant: KOWA CO

Inventor： SHIBUYA K ,  KAWAMINE KATSUMI ,  SATO YUKIHIRO ,  MIURA TORU ,  OZAKI CHIYOKA ,  EDANO TOSHIYUKI ,  HIRATA MITSUTERU

IPC: C07D413/12 ,  A61K31/496 ,  A61K31/506 ,  A61K31/55 ,  A61K31/5513 ,  A61P3/06 ,  A61P9/00 ,  A61P9/10 ,  C07D233/70 ,  C07D235/28 ,  C07D263/58 ,  C07D277/74 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D498/04 ,  C07D513/04 ,  C07F9/6509 ,  C07F9/6558 ,  A61K31/495 ,  A61K31/505 ,  C07D277/80 ,  C07D413/04

CPC classification number: C07D263/58 ,  C07D235/28 ,  C07D277/74 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12 ,  C07F9/650958 ,  C07F9/65583

Abstract: Compounds represented by formula (I) and salts or solvates of these, each being useful especially as an acyl coenzyme A cholesterol acyltransferase (ACAT) inhibitor, wherein (a) represents an optionally substituted divalent residue of benzene, pyridine, cyclohexane or naphthalene, or vinylene; Ar represents optionally substituted aryl; X represents -NH-, oxygen, or sulfur; Y represents -NR1-, oxygen, sulfur, sulfoxide, or sulfone; Z represents a single bond or -NR2-; R1 and R2 each represents hydrogen, optionally substituted lower alkyl, optionally substituted aryl, or optionally substituted lower silylalkyl; l is an integer of 0 to 15; m is 2 or 3; and n is an integer of 0 to 3.