1-pyridazinyl-hydroxyimino- 3- phenyl- propanes as GPBAR1 agonistsThis invention relates to 1-pyridazinyl-hydroxyimino-3-phenyl-propanes of the formula (I) wherein R1 to R7 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and may therefore be useful as medicaments for the treatment of diseases such as type II diabetes.The compound of following formulawhereinr 1it is the heteroaryl that selects the group of free the following composition: pyridazine-4-base, 3-oxo-2,3-dihydro-pyridazine-4-base and 6-oxo-1,6-dihydrogen dazin-3-base, described heteroaryl is unsubstituted or is independently selected from one of the group that is comprised of the following, two or three groups and replaces: c 1-7-alkyl, halogen, halogen-c 1-7-alkyl, hydroxyl, hydroxyl-c 1-7-alkyl, c 1-7-alkoxyl group and c 1-7-alkoxy-c 1-7-alkyl; r 2the group of selecting free the following to form: c 1-7-alkyl, c 3-7-cycloalkyl, c 2-7-thiazolinyl, halogen-c 1-7-alkyl, the phenyl that one, two or three group of the group that unsubstituted phenyl or be independently selected from is comprised of the following replaces: c 1-7-alkyl, halogen, halogen-c 1-7-alkyl, halogen-c 1-7-alkoxyl group and c 1-7-alkyl sulphonyl, and heteroaryl, described heteroaryl is unsubstituted or by c 1-7-alkyl or oxo base replace, r 3and r 7be independently from each other the group being formed by the following: hydrogen, halogen and c 1-7-alkyl; and r 4, r 5and r 6independently selected from the group being formed by the following: hydrogen,halogen, halogen-c 1-7-alkyl, cyano group, cyano group-c 1-7-alkyl, c 1-7-alkyl, c 3-7-thiazolinyl, c 1-7-alkynyl, c 1-7-alkoxyl group, c 1-7-alkoxy-c 1-7-alkyl, hydroxyl, hydroxyl-c 1-7-alkyl, hydroxyl-c 3-7-thiazolinyl, hydroxyl-c 3-7-alkynyl, hydroxyl-c 1-7-alkoxyl group, carboxyl, carboxyl-c 1-7-alkyl, carboxyl-c 3-7-thiazolinyl, carboxyl-c 1-7-alkynyl, carboxyl-c 1-7-alkoxyl group, tetrazyl,c 1-7-alkoxy carbonyl, c 1-7-alkyl sulphonyl, c 1-7-alkyl sulphonyl oxygen base, c 1-7-alkyl sulfonyl-amino, c 3-7-naphthene sulfamide base is amino, amino-sulfonyl, (c 1-7-alkyl)-amino-sulfonyl, two-(c 1-7-alkyl)-amino-sulfonyl, heterocyclic radical alkylsulfonyl, c 1-7-alkyl-amino, two-(c 1-7-alkyl)-amino, c 1-7-alkoxy-c 1-7-alkyl-amino, c 1-7-alkoxy-c 1-7-alkyl-c 1-7-alkyl-amino, c 1-7-alkoxyl group-halogen-c 1-7-alkyl-amino, hydroxyl-c 1-7-alkyl-c 1-7-alkyl-amino, by the amino acid whose amino amino acid connecting, c 3-7-cycloalkyl-amino, wherein c 3-7-cycloalkyl is unsubstituted or by hydroxyl, hydroxyl-c 1-7-alkyl or carboxyl substituted, carboxyl-c 1-7-alkyl-aminocarboxyl, carboxyl-c 1-7-alkyl-(c 1-7-alkyl)-aminocarboxyl, c 1-7-alkoxy carbonyl-c 1-7-alkyl-aminocarboxyl, c 1-7-alkyl-aminocarboxyl, two-(c 1-7-alkyl)-aminocarboxyl, c 1-7-alkyl sulphonyl-c 1-7-alkyl-aminocarboxyl, halogen-c 1-7-alkyl-aminocarboxyl, hydroxyl-c 1-7-alkyl-aminocarboxyl, hydroxyl-c 1-7-alkyl-c 1-7-alkyl-aminocarboxyl, halogen-hydroxyl-c 1-7-alkyl-aminocarboxyl, c 1-7-alkoxy-c 1-7-alkyl-aminocarboxyl, c 3-7-cycloalkyl amino carbonyl, wherein c 3-7-cycloalkyl is unsubstituted or by hydroxyl, hydroxyl-c 1-7-alkyl or carboxyl substituted, heterocyclic radical-aminocarboxyl, wherein heterocyclic radical is unsubstituted or by c 1-7-alkyl or oxo base replace, heterocyclic radical-c 1-7-alkyl-aminocarboxyl, wherein heterocyclic radical is unsubstituted or by c 1-7-alkyl or oxo base replace, hydroxyl-c 1-7-alkyl-aminocarboxyl-c 1-7-alkyl, c 1-7-alkoxy carbonyl-c 1-7-alkyl, two-(c 1-7-alkoxy carbonyl)-c 1-7-alkyl, c 1-7-alkyl-carbonyl-amino-c 1-7-alkyl amino-carbonyl, c 1-7-alkyl-carbonyl-amino, carboxyl-c 1-7-alkyl-carbonyl-amino, c 1-7-alkoxy carbonyl-c 1-7-alkyl-carbonyl-amino, c 3-7-cycloalkyl, wherein c 3-7-cycloalkyl is unsubstituted or by hydroxyl, hydroxyl-c 1-7-alkyl or carboxyl substituted, c 3-7-cycloalkyl-c 1-7-alkyl, wherein c 3-7-cycloalkyl is unsubstituted or by hydroxyl, hydroxyl-c 1-7-alkyl or carboxyl substituted, heterocyclic radical, described heterocyclic radical is unsubstituted or by c 1-7-alkyl, halogen, hydroxyl, hydroxyl-c 1-7-alkyl, c 1-7-alkoxyl group, oxo base, carboxyl, carboxyl-c 1-7-alkyl, c 1-7-alkoxy carbonyl, aminocarboxyl, c 1-7-alkyl sulphonyl, amino-sulfonyl, c 1-7-alkyl-carbonyl, carboxyl-c 1-7-alkyl-aminocarboxyl or hydroxyl alkylsulfonyl-c 1-7-alkyl-aminocarboxyl replaces, heterocyclic radical carbonyl, described heterocyclic radical is unsubstituted or by c 1-7-alkyl, halogen, hydroxyl, hydroxyl-c 1-7-alkyl, c 1-7-alkoxyl group, oxo base, carboxyl, carboxyl-c 1-7-alkyl or c 1-7-alkyl sulphonyl replaces, heteroaryl, described heteroaryl is unsubstituted or by c 1-7-alkyl, c 3-7-cycloalkyl, thp trtrahydropyranyl, carboxyl, carboxyl-c 1-7-alkyl, c 1-7-alkoxy-c 1-7-alkyl or c 1-7-alkoxy carbonyl replaces, phenyl oxygen base, wherein phenyl is unsubstituted or is selected from that one to three group of halogen or carboxyl replaces, andphenyl, described phenyl is that one to three group of the group of unsubstituted or selected free the following composition replaces: halogen, c 1-7-alkyl, hydroxyl, hydroxyl-c 1-7-alkyl, cyano group, cyano group-c 1-7-alkyl, amino, c 1-7-alkoxyl group, carboxyl, carboxyl-c 1-7-alkyl, c 1-7-alkoxyl group-carbonyl, tetrazyl, carboxyl-c 1-7-alkyl-carbonylamino, c 1-7-alkoxyl group-carbonyl-c 1-7-alkyl-carbonyl...
GPBAR1 작용제로서의 1-피리다지닐-하이드록시이미노-3-페닐-프로판본 발명은 하기 화학식 I의 1-피리다지닐-하이드록시이미노-3-페닐-프로판 뿐만 아니라 이의 약학적으로 허용가능한 염에 관한 것이다. 본 화합물은 GPBAR1 작용제이고, 따라서 질환, 예컨대 제2형 당뇨병의 치료용 약제로서 유용할 수 있다: 화학식 I 상기 식에서, R1 내지 R7은 명세서 및 특허청구범위에 정의된 바와 같다.하기 화학식 I의 화합물 또는 이의 약학적으로 허용가능한 염:화학식 I[이미지]상기 식에서,R1은 피리다진-4-일, 3-옥소-2,3-다이하이드로-피리다진-4-일 및 6-옥소-1,6-다이하이드로피리다진-3-일로 구성된 군으로부터 선택되는 헤테로아릴이되, 상기 헤테로아릴은 비치환되거나 C1-7-알킬, 할로겐, 할로겐-C1-7-알킬, 하이드록시, 하이드록시-C1-7-알킬, C1-7-알콕시 및 C1-7-알콕시-C1-7-알킬로 구성된 군으로부터 독립적으로 선택되는 1, 2 또는 3개의 기로 치환되고;R2는 C1-7-알킬, C3-7-사이클로알킬, C2-7-알케닐, 할로겐-C1-7-알킬, 비치환된 페닐 또는 C1-7-알킬, 할로겐, 할로겐-C1-7-알킬, 할로겐-C1-7-알콕시 및 C1-7-알킬설포닐로 구성된 군으로부터 독립적으로 선택되는 1, 2 또는 3개의 기로 치환된 페닐, 및 비치환되거나 C1-7-알킬 또는 옥소로 치환된 헤테로아릴로 구성된 군으로부터 선택되고;R3 및 R7은 각각 수소, 할로겐 및 C1-7-알킬로 구성된 군으로부터 독립적으로 선택되고;R4, R5 및 R6은 수소, 할로겐, 할로겐-C1-7-알킬, 시아노, 시아노-C1-7-알킬, C1-7-알킬, C3-7-알케닐, C1-7-알키닐, C1-7-알콕시, C1-7-알콕시-C1-7-알킬, 하이드록시, 하이드록시-C1-7-알킬, 하이드록시-C3-7-알케닐, 하이드록시-C3-7-알키닐, 하이드록시-C1-7-알콕시, 카복실, 카복실-C1-7-알킬, 카복실-C3-7-알케닐, 카복실-C1-7-알키닐, 카복실-C1-7-알콕시, 테트라졸릴, C1-7-알콕시카보닐, C1-7-알킬설포닐, C1-7-알킬설포닐옥시, C1-7-알킬설포닐아미노, C3-7-사이클로알킬설포닐아미노, 아미노설포닐, (C1-7-알킬)-아미노설포닐, 다이-(C1-7-알킬)-아미노설포닐, 헤테로사이클릴설포닐, C1-7-알킬-아미노, 다이-(C1-7-알킬)-아미노, C1-7-알콕시-C1-7-알킬-아미노, C1-7-알콕시-C1-7-알킬-C1-7-알킬-아미노, C1-7-알콕시-할로겐-C1-7-알킬-아미노, 하이드록시-C1-7-알킬-C1-7-알킬-아미노, 아미노산의 아미노 기를 통해 부착된 아미노산,C3-7-사이클로알킬이 비치환되거나 하이드록시, 하이드록시-C1-7-알킬 또는 카복실로 치환된 C3-7-사이클로알킬-아미노,카복실-C1-7-알킬-아미노카보닐, 카복실-C1-7-알킬-(C1-7-알킬)-아미노카보닐, C1-7-알콕시카보닐-C1-7-알킬-아미노카보닐, C1-7-알킬-아미노카보닐, 다이-(C1-7-알킬)-아미노카보닐, C1-7-알킬설포닐-C1-7-알킬-아미노카보닐, 할로겐-C1-7-알킬-아미노카보닐, 하이드록시-C1-7-알킬-아미노카보닐, 하이드록시-C1-7-알킬-C1-7-알킬-아미노카보닐, 할로겐-하이드록시-C1-7-알킬-아미노카보닐, C1-7-알콕시-C1-7-알킬-아미노카보닐, C3-7-사이클로알킬이 비치환되거나 하이드록시, 하이드록시-C1-7-알킬 또는 카복실로 치환된 C3-7-사이클로알킬아미노카보닐,헤테로사이클릴이 비치환되거나 C1-7-알킬 또는 옥소로 치환된 헤테로사이클릴-아미노카보닐,헤테로사이클릴이 비치환되거나 C1-7-알킬 또는 옥소로 치환된 헤테로사이클릴-C1-7-알킬-아미노카보닐,하이드록시-C1-7-알킬-아미노카보닐-C1-7-알킬, C1-7-알콕시카보닐-C1-7-알킬, 다이-(C1-7-알콕시카보닐)-C1-7-알킬, C1-7-알킬카보닐아미노-C1-7-알킬아미노카보닐, C1-7-알킬카보닐아미노, 카복실-C1-7-알킬카보닐아미노, C1-7-알콕시카보닐-C1-7-알킬카보닐아미노,비치환되거나 하이드록시, 하이드록시-C1-7-알킬 또는 카복실로 치환된 C3-7-사이클로알킬,C3-7-사이클로알킬이 비치환되거나 하이드록시, 하이드록시-C1-7-알킬 또는 카복실로 치환된 C3-7-사이클로알킬-C1-7-알킬,비치환되거나 C1-7-알킬, 할로겐, 하이드록시, 하이드록시-C1-7-알킬, C1-7-알콕시, 옥소, 카복실, 카복실-C1-7-알킬, C1-7-알콕시카보닐, 아미노카보닐, C1-7-알킬설포닐, 아미노설포닐, C1-7-알킬카보닐, 카복실-C1-7-알킬-아미노카보닐 또는 하이드록시설포닐-C1-7-알킬-아미노카보닐로 치환된 헤테로사이클릴,헤테로사이클릴이 비치환되거나 C1-7-알킬, 할로겐, 하이드록시, 하이드록시-C1-7-알킬, C1-7-알콕시, 옥소, 카복실, 카복실-C1-7-알킬 또는 C1-7-알킬설포닐로 치환된 헤테로사이클릴카보닐,비치환되거나 C1-7-알킬, C3-7-사이클로알킬, 테트라하이드로피라닐, 카복실, 카복실-C1-7-알킬, C1-7-알콕시-C1-7-알킬 또는 C1-7-알콕시카보닐로 치환된 헤테로아릴,페닐이 비치환되거나 할로겐 및 카복실로부터 선택되는 1 내지 3개의 기로 치환된 페닐옥시, 및비치환되거나 할로겐, C1-7-알킬, 하이드록시, 하이드록시-C1-7-알킬, 시아노, 시아노-C1-7-알킬, 아미노, C1-7-알콕시, 카복실, 카복실-C1-7-알킬, C1-7-알콕시-카보닐, 테트라졸릴, 카복실-C1-7-알킬-카보닐아미노, C1-7-알콕시-카보닐-C1-7-알킬-카보닐아미노, C1-7-알킬설포닐, C1-7-알킬-설포닐아미노, 아미노설포닐, C1-7-알킬-아미노설포닐, 다이-(C1-7-알킬)-아미노설포닐, 헤테로사이클릴설포닐, C1-7-알콕시카보닐-C1-7-알콕시, C1-7-알콕시카보닐-C1-7-알킬-아미노카보닐, 카복실-C1-7-알킬-아미노카보닐, C1-7-알콕시카보닐-C1-7-알킬-카보닐아미노-C1-7-알킬설포닐, 페닐-C1-7-알킬-아미노카보닐, 테트라졸릴-아미노카보닐, 테트라졸릴-C1-7-알킬-아미노카보닐 및 카복실-C1-7-알킬-아미노카보닐로 구성된 군으로부터 선택되는 1 내지 3개의 기로 치환된 페닐로 구성된 군으로부터 독립적으로 선택된다.