NOVEL THIOPHENE DERIVATIVESThe invention relates to novel thiophene derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents.A compound selected from the group consisting of thiophenes of the Formula (I),Formula (I)whereinR1 represents hydrogen, lower alkyl, lower alkoxy, or halogen;R2 represents hydrogen, lower alkyl, lower alkoxy, or halogen;R3 represents hydrogen, hydroxy-lower alkyl, 2,3-dihydroxypropyl, di-(hydroxy-lower alkyl)-lower alkyl, -CH2-(CH2)K-NR31R32, (azetidine-3-carboxylic acid)-1 -yl-methyl, (azetidine-3-carboxylic acid lower alkylester)-1 -yl-methyl, 2-[(azetidine-3-carboxylic acid)-1 -yl]-ethyl, 2-[(azetidine-3-carboxylic acid lower alkylester)-1 -yl]-ethyl, 3- [(azetidine-3-carboxylic acid)-1 -yl]-propyl, 3-[(azetidine-3-carboxylic acid lower alkylester)-1 -yl]-propyl, (pyrrolidine-3-carboxylic acid)-1 -yl-methyl, (pyrrolidine-3- carboxylic acid lower alkylester)-1 -yl-methyl, (pyrrolidine-2-carboxylic acid)-1 -yl- methyl, (pyrrolidine-2-carboxylic acid lower alkylester)-1 -yl-methyl, 2-[(pyrrolidine-3- carboxylic acid)-1 -yl]-ethyl, 2-[(pyrrolidine-3-carboxylic acid lower alkylester)-1 -yl]- ethyl, 2-[(pyrrolidine-2-carboxylic acid)-1 -yl]-ethyl, 2-[(pyrrolidine-2-carboxylic acid lower alkylester)-1 -yl]-ethyl, 3-[(pyrrolidine-3-carboxylic acid)-1 -yl]-propyl, 3- [(pyrrolidine-3-carboxylic acid lower alkylester)-1 -yl]-propyl, 3-[(pyrrolidine-2- carboxylic acid)-1 -yl]-propyl, 3-[(pyrrolidine-2-carboxylic acid lower alkylester)-1 -yl]- propyl, -CH2-(CH2)n-CONR31R32, -CO-NHR31, 1 -(1 -(3-carboxy-azetidinyl))-2acetyl, 1 - (1 -(2-carboxy-pyrrolidinyl))-2-acetyl, 1 -(1 -(3-carboxy-pyrrolidinyl))-2-acetyl, 1 -(1 -(3- carboxy-azetidinyl))-3-propionyl, 1 -(1 -(2-carboxy-pyrrolidinyl))-3-propionyl, 1 -(1 -(3- carboxy-pyrrolidinyl))-3-propionyl, -(CH2)HCH(OH)-CH2-NR31R32, hydroxy, lower alkoxy, fluoro-lower alkoxy, hydroxy-lower alkoxy, di-(hydroxy-lower alkyl)-lower alkoxy, 1 -glyceryl, 2-glyceryl, 2-hydroxy-3-methoxy-propoxy, -OCH2-(CH2)m- NR31R32, 2-pyrrolidin-1 -yl-ethoxy, 3-pyrrolidin-1 -yl-propoxy, 2-piperazin-1 -yl-ethoxy, 2-[4-(lower alkyl)-piperazin-1 -yl]-ethoxy, 2-[4-(2-hydroxy-ethyl)-piperazin-1 -yl]- ethoxy, 3-piperazin-1 -yl-propoxy, 3-[4-(lower alkyl)-piperazin-1 -yl]-propoxy, 3-[4-(2- hydroxy-ethyl)-piperazin-1 -yl]-propoxy, 2-morpholin-4-yl-ethoxy, 3-morpholin-4-yl- propoxy, 2-[(azetidine-3-carboxylic acid)-1 -yl]-ethoxy, 2-[(azetidine-3-carboxylic acid lower alkylester)-1 -yl]-ethoxy, 2-[(pyrrolidine-3-carboxylic acid)-1 -yl]-ethoxy, 2- [(pyrrolidine-3-carboxylic acid lower alkylester)-1 -yl]-ethoxy, 2-[(pyrrolidine-2- carboxylic acid)-1 -yl]-ethoxy, 2-[(pyrrolidine-2-carboxylic acid lower alkylester)-1 -yl]- ethoxy, 2-[(2-hydroxy-pyrrolidine)-1 -yl]-ethoxy, 2-[(3-hydroxy-pyrrolidine)-1 -yl]- ethoxy, 3-[(azetidine-3-carboxylic acid)-1 -yl]-propoxy, 3-[(azetidine-3-carboxylic acid lower alkylester)-1 -yl]-propoxy, 3-[(pyrrolidine-3-carboxylic acid)-1 -yl]-propoxy, 3- [(pyrrolidine-3-carboxylic acid lower alkylester)-1 -yl]-propoxy, 3-[(pyrrolidine-2- carboxylic acid)-1 -yl]-propoxy, 3-[(pyrrolidine-2-carboxylic acid lower alkylester)-1 - yl]-propoxy, 3-[(2-hydroxy-pyrrolidine)-1 -yl]-propoxy, 3-[(3-hydroxy-pyrrolidine)-1 -yl]- propoxy, 2-amino-3-hydroxy-2-hydroxymethyl-propoxy, -0-CH2-CONR31R32, 1 -(1 -(3- carboxy-azetidinyl))-1 -oxo-2-ethoxy, 1 -(1 -(pyrrolidine-2-carboxylic acid)-1 -yl)-1 -oxo- 2-ethoxy, 1 -(1 -(pyrrolidine-3-carboxylic acid)-1 -yl)-1 -oxo-2-ethoxy, 3-carbamoyl- propoxy, 3-(lower alkylcarbamoyl)propoxy, 3-(2-hydroxyethylcarbamoyl)propoxy, -OCH2-CH(OH)-CH2-NR31 R32, 3-[(azetidine-3-carboxylic acid)-1 -yl]-2- hydroxypropoxy, 3-[(azetidine-3-carboxylic acid lower alkylester)-1 -yl]-2- hydroxypropoxy, 2-hydroxy-3-[(pyrrolidine-3-carboxylic acid)-1 -yl]-propoxy, 2- hydroxy-3-[(pyrrolidine-3-carboxylic acid lower alkylester)-1 -yl]-propoxy, 2-hydroxy- 3-[(pyrrolidine-2-carboxylic acid)-1 -yl]-propoxy, 2-hydroxy-3-[(pyrrolidine-2- carboxylic acid lower alkylester)-1 -yl]-propoxy, 2-hydroxy-3-[(2-hydroxy-pyrrolidine)- 1 -yl]-propoxy, 2-hydroxy-3-[(3-hydroxy-pyrrolidine)-1 -yl]-propoxy, 2-hydroxy-3- pyrrolidin-1 -yl-propoxy, 2-hydroxy-3-piperazin-1 -yl-propoxy, 2-hydroxy-3-[4-(lower alkyl)-piperazin-1 -yl]-propoxy, 2-hydroxy-3-[4-(2-hydroxy-ethyl)-piperazin-1 -yl]- propoxy, 2-hydroxy-3-morpholin-4-yl-propoxy, -NR31R32, -NHCO-R31, -CH2-(CH2)k- NHSO2R33, -(CH2)nCH(OH)-CH2-NHSO2R33, -OCH2-(CH2)m-NHSO2R33, -OCH2- CH(OH)-CH2-NHSO2R33, -CH2-(CH2)k-NHCOR34, -(CH2)nCH(OH)-CH2-NHCOR34, -OCH2-(CH2)m-NHCOR34, or -OCH2-CH(OH)-CH2-NHCOR34;R31 represents hydrogen, methyl, ethyl, 1 -propyl, 2-propyl, 2-hydroxyethyl, 2- hydroxy-1 -hydroxymethyl-ethyl, 2-lower alkoxyethyl, 3-hydroxypropyl, 3-lower alkoxypropyl, 2-aminoethyl, 2-(lower alkylamino)ethyl, 2-(di-(lower alkyl)amino)ethyl, carboxymethyl, lower alkylcarboxymethyl, 2-carboxyethyl, or 2-(lower alkylcarboxy)ethyl;R32 represents hydrogen or methyl;R33 represents methyl, ethyl, propyl, isopropyl, butyl, 2-hydroxyethyl, 2-methoxyethyl, methylamino, ethylamino, propylamino, isopropylamino, n-butylamino, or dimethylamino;R34 represents hydroxymethyl, hy...
신규한 티오펜 유도체 본원발명은 신규한 티오펜 유도체, 그 제조방법 및 약제학적으로 활성인 화합물로서의 이들의 용도에 관한 것이다. 상기 화합물은 면역 억제제로서 특히 활성이다.  화학식 (I)의 티오펜으로 구성된 그룹으로부터 선택되는 화합물:  화학식 (I) 여기서 R1 은 수소, 저급 알킬, 저급 알콕시, 또는 할로겐을 나타내며; R2 은 수소, 저급 알킬, 저급 알콕시, 또는 할로겐을 나타내며; R3 은 수소, 하이드록시-저급 알킬, 2,3-디하이드록시프로필, 디-(하이드록시-저급 알킬)-저급 알킬, -CH2-(CH2)k-NR31R32, (아제티딘-3-카르복실릭 애시드)-1-일-메틸, (아제티딘-3-카르복실릭 애시드 저급 알킬에스테르)-1-일-메틸, 2-[(아제티딘-3-카르복실릭 애시드)-1-일]-에틸, 2-[(아제티딘-3-카르복실릭 애시드 저급 알킬에스테르)-1-일]-에틸, 3-[(아제티딘-3-카르복실릭 애시드)-1-일]-프로필, 3-[(아제티딘-3-카르복실릭 애시드 저급 알킬에스테르)-1-일]-프로필, (피롤리딘-3-카르복실릭 애시드)-1-일-메틸, (피롤리딘-3-카르복실릭 애시드 저급 알킬에스테르)-1-일-메틸, (피롤리딘-2-카르복실릭 애시드)-1-일-메틸, (피롤리딘-2-카르복실릭 애시드 저급 알킬에스테르)-1-일-메틸, 2-[(피롤리딘-3-카르복실릭 애시드)-1-일]-에틸, 2-[(피롤리딘-3-카르복실릭 애시드 저급 알킬에스테르)-1-일]-에틸, 2-[(피롤리딘-2-카르복실릭 애시드)-1-일]-에틸, 2-[(피롤리딘-2-카르복실릭 애시드 저급 알킬에스테르)-1-일]-에틸, 3-[(피롤리딘-3-카르복실릭 애시드)-1-일]-프로필, 3-[(피롤리딘-3-카르복실릭 애시드 저급 알킬에스테르)-1-일]-프로필, 3-[(피롤리딘-2-카르복실릭 애시드)-1-일]-프로필, 3-[(피롤리딘-2-카르복실릭 애시드 저급 알킬에스테르)-1-일]-프로필, -CH2-(CH2)n-CONR31R32, -CO-NHR31, 1-(1-(3-카르복시-아제티딘일))-2-아세틸, 1-(1-(2-카르복시-피롤리딘일))-2-아세틸, 1-(1-(3-카르복시-피롤리딘일))-2-아세틸, 1-(1-(3-카르복시-아제티딘일))-3-프로피온일, 1-(1-(2-카르복시-피롤리딘일))-3-프로피온일, 1-(1-(3-카르복시-피롤리딘일))-3-프로피온일, -(CH2)nCH(OH)-CH2-NR31R32, 하이드록시, 저급 알콕시, 플루오로-저급 알콕시, 하이드록시-저급 알콕시, 디-(하이드록시-저급 알킬)-저급 알콕시, 1-글리세릴, 2-글리세릴, 2-하이드록시-3-메톡시-프로폭시, -OCH2-(CH2)m-NR31R32, 2-피롤리딘-1-일-에톡시, 3-피롤리딘-1-일-프로폭시, 2-피레라진-1-일-에톡시, 2-[4-(저급 알킬)-피레라진-1-일]-에톡시, 2-[4-(2-하이드록시-에틸)-피레라진-1-일]-에톡시, 3-피레라진-1-일-프로폭시, 3-[4-(저급 알킬)-피레라진-1-일]-프로폭시, 3-[4-(2-하이드록시-에틸)-피레라진-1-일]-프로폭시, 2-모폴린-4-일-에톡시, 3-모폴린-4-일-프로폭시, 2-[(아제티딘-3-카르복실릭 애시드)-1-일]-에톡시, 2-[(아제티딘-3-카르복실릭 애시드 저급 알킬에스테르)-1-일]-에톡시, 2-[(피롤리딘-3-카르복실릭 애시드)-1-일]-에톡시, 2-[(피롤리딘-3-카르복실릭 애시드 저급 알킬에스테르)-1-일]-에톡시, 2-[(피롤리딘-2-카르복실릭 애시드)-1-일]-에톡시, 2-[(피롤리딘-2-카르복실릭 애시드 저급 알킬에스테르)-1-일]-에톡시, 2-[(2-하이드록시-피롤리딘)-1-일]-에톡시, 2-[(3-하이드록시-피롤리딘)-1-일]-에톡시, 3-[(아제티딘-3-카르복실릭 애시드)-1-일]-프로폭시, 3-[(아제티딘-3-카르복실릭 애시드 저급 알킬에스테르)-1-일]-프로폭시, 3-[(피롤리딘-3-카르복실릭 애시드)-1-일]-프로폭시, 3-[(피롤리딘-3-카르복실릭 애시드 저급 알킬에스테르)-1-일]-프로폭시, 3-[(피롤리딘-2-카르복실릭 애시드)-1-일]-프로폭시, 3-[(피롤리딘-2-카르복실릭 애시드 저급 알킬에스테르)-1-일]-프로폭시, 3-[(2-하이드록시-피롤리딘)-1-일]-프로폭시, 3-[(3-하이드록시-피롤리딘)-1-일]-프로폭시, 2-아미노-3-하이드록시-2-하이드록시메틸-프로폭시, -O-CH2-CONR31R32, 1-(1-(3-카르복시-아제티딘일))-1-옥소-2-에톡시, 1-(1-(피롤리딘-2-카르복실릭 애시드)-1-일)-1-옥소-2-에톡시, 1-(1-(피롤리딘-3-카르복실릭 애시드)-1-일)-1-옥소-2-에톡시, 3-카르바모일-프로폭시, 3-(저급 알킬카르바모일)프로폭시, 3-(2-하이드록시에틸카르바모일)프로폭시, -OCH2-CH(OH)-CH2-NR31R32, 3-[(아제티딘-3-카르복실릭 애시드)-1-일]-2-하이드록시프로폭시, 3-[(아제티딘-3-카르복실릭 애시드 저급 알킬에스테르)-1-일]-2-하이드록시프로폭시, 2-하이드록시-3-[(피롤리딘-3-카르복실릭 애시드)-1-일]-프로폭시, 2-하이드록시-3-[(피롤리딘-3-카르복실릭 애시드 저급 알킬에스테르)-1-일]-프로폭시, 2-하이드록시-3-[(피롤리딘-2-카르복실릭 애시드)-1-일]-프로폭시, 2-하이드록시-3-[(피롤리딘-2-카르복실릭 애시드 저급 알킬에스테르)-1-일]-프로폭시, 2-하이드록시-3-[(2-하이드록시-피롤리딘)-1-일]-프로폭시, 2-하이드록시-3-[(3-하이드록시-피롤리딘)-1-일]-프로폭시, 2-하이드록시-3-피롤리딘-1-일-프로폭시, 2-하이드록시-3-피레라진-1-일-프로폭시, 2-하이드록시-3-[4-(저급 알킬)-피레라진-1-일]-프로폭시, 2-하이드록시-3-[4-(2-하이드록시-에틸)-피레라진-1-일]-프로폭시, 2-하이드록시-3-모폴린-4-일-프로폭시, -NR31R32, -NHCO-R31, -CH2-(CH2)k-NHSO2R33, -(CH2)nCH(OH)-CH2-NHSO2R33, -OCH2-(CH2)m-NHSO2R33, -OCH2-CH(OH)-CH2-NHSO2R33, -CH2-(CH2)k-NHCOR34, -(CH2)nCH(OH)-CH2-NHCOR34, -OCH2-(CH2)m-NHCOR34, 또는 -OCH2-CH(OH)-CH2-NHCOR34를 나타내며; R31 은 수소, 메틸, 에틸, 1-프로필, 2-프로필, 2-하이드록시에틸, 2-하이드록시-1-하이드록시메틸-에틸, 2-저급 알콕시에틸, 3-하이드록시프로필, 3-저급 알콕시프로필, 2-아미노에틸, 2-(저급 알킬아미노)에틸, 2-(디-(저급 알킬)아미노)에틸, 카르복시메틸, 저급 알킬카르복시메틸, 2-카르복시에틸, 또는 2-(저급 알킬카르복시)에틸을 나타내며; R32 는 수소 또는 메틸을 나타내며; R33 은 메틸, 에틸, 프로필, 이소프로필, 부틸, 2-하이드록시에틸, 2-메톡시에틸, 메틸아미노, 에틸아미노, 프로필아미노, 이소프로필아미노, n-부틸아미노, 또는 디메틸아미노를 나타내며; R34 는 하이드록시메틸, 하이드록시에틸, 아미노메틸, 메틸아미노메틸, 디메틸아미노메틸, 아미노에틸, 2-메틸아미노-에틸, 또는 2-디메틸아미노-에틸을 나타내며; k 는 정수 1, 2, 또는 3을 나타내며; m 은 정수 1 또는 2를 나타내며; n 은 정수 0, 1, 또는 2를 나타내며; R4는 수소, 저급 알킬 또는 할로겐을 나타내며; R5 는 트리플루오로메틸, 메틸, 에틸, 또는 프로필을 나타내며; R6 은 페닐을 나타내며, 선택적으로 모노- 또는 디-치환되며, 여기서 치환체는 독립적으로 메틸, 에틸, 트리플루오로메틸, 할로겐 및 메톡시로부터 선택되며; 또는 2-, 3- 또는 4-피리딜을 나타내며, 선택적으로 메틸 또는 메톡시로 치환되며; 그리고 R7 은 수소, 또는 메틸을 나타냄; 및 이들의 광학적으로 순수한 거울상이성질체, 라세메이트와 같은 거울상이성질체의 혼합물, 부분입체이성질체, 부분입체이성질체의 혼합물, 부분입체이성질체성 라세메이트, 및 부분입체이성질체성 라세메이트의 혼합물, 뿐만 아니라 이들 화합물의 염 및 용매화물, 및 형택학적 형태(morphological form). 