Tetrahydroquinolinones and their use as modulators of metabotropic glutamate receptorsThe invention relates to ethynyl-substituted tetrahydroquinolinone derivatives as well as their pharmaceutically acceptable a salts. The invention further relates to a process for the preparation of such compounds. The compounds of the invention are group I mGIuR modulators and are therefore useful for the control and prevention of acute and/or chronic neurological disorders.The compound of formula i,whereinr 1expression aryl or heteroaryl; r 2and r 3, it can be identical or different, expression hydrogen or c 1-6alkyl; r 4and r 5, it can be identical or different, expression hydrogen or c 1-6alkyl; should be appreciated that:aryl is represented benzyl ring that is unsubstituted or the benzyl ring that replaces through 1,2,3,4 or 5 substituting group, and it can be identical or different, and its substituting group is to be selected from the c that replaces through one or more fluorine, chlorine or bromine atom by arbitrarily 1-6alkyl, the c that replaces through one or more fluorine, chlorine or bromine atom arbitrarily 1-6alkoxyl group, ring c 3-12alkyl, hydroxyl, f, cl, br, i, cn, nitro, two-c 1-6alkylamino, n-encircle c 3-12alkyl-n-c 1-6alkylamino, azetidine base, pyrrolidyl, piperidyl, morpholinyl, 4-c 1-6the group that alkyl-piperazinyl, tetrazyl,  azoles base, furyl, pyrryl, thienyl, different  azoles base, thiazolyl, imidazolyl,  di azoly, pyridyl, pyrimidyl and phenyl are formed; heteroaryl represents to have from 1 to 4 heteroatomic (mixing) aromatics 5-, 6-or 7-unit ring, this heteroatoms is independently selected from oxygen, nitrogen and sulphur, wherein this encircles to being unsubstituted or can be identical or different substituting group through 1,2 or 3 and replaces, and its substituting group is to be selected from the c that replaces through one or more fluorine, chlorine or bromine atom by arbitrarily 1-6alkyl, the c that replaces through one or more fluorine, chlorine or bromine atom arbitrarily 1-6alkoxyl group, ring c 3-12alkyl, hydroxyl, f, cl, br, i, cn, nitro, two-c 1-6alkylamino, n-encircle c 3-12alkyl-n-c 1-6alkylamino, azetidine base, pyrrolidyl, piperidyl, morpholinyl, 4-c 1-6the group that alkyl-piperazinyl, tetrazyl,  azoles base, furyl, pyrryl, thienyl, different  azoles base, thiazolyl, imidazolyl,  di azoly, pyridyl, pyrimidyl and phenyl are formed; and the compound of formula i can not be represented:2-phenylacetylene base-7,8-dihydro-6h-quinoline-5-ketone2-pyridin-3-yl ethynyl-7,8-dihydro-6h-quinoline-5-ketonetolyl ethynyl-7 between 2-, 8-dihydro-6h-quinoline-5-ketone2-(3-hydroxyl-phenylacetylene base)-7,8-dihydro-6h-quinoline-5-ketone2-(3-methoxyl group-phenylacetylene base)-7,8-dihydro-6h-quinoline-5-ketone2-(3-fluoro-phenylacetylene base)-7,8-dihydro-6h-quinoline-5-ketone2-(3-chloro-phenylacetylene base)-7,8-dihydro-6h-quinoline-5-ketone2-(3-bromo-phenylacetylene base)-7,8-dihydro-6h-quinoline-5-ketone3-(5-oxo-5,6,7,8-tetrahydrochysene-quinoline-2-ethyl-acetylene base)-benzonitrile2-thiazole-5-ethyl-acetylene base-7,8-dihydro-6h-quinoline-5-ketone2- azoles-5-ethyl-acetylene base-7,8-dihydro-6h-quinoline-5-ketone7,7-dimethyl-2-pyridin-3-yl ethynyl-7,8-dihydro-6h-quinoline-5-ketone7, tolyl ethynyl-7 between 7-dimethyl-2-, 8-dihydro-6h-quinoline-5-ketone2-(3-hydroxyl-phenylacetylene base)-7,7-dimethyl-7,8-dihydro-6h-quinoline-5-ketone2-(3-methoxyl group-phenylacetylene base)-7,7-dimethyl-7,8-dihydro-6h-quinoline-5-ketone2-(3-fluoro-phenylacetylene base)-7,7-dimethyl-7,8-dihydro-6h-quinoline-5-ketone2-(3-chloro-phenylacetylene base)-7,7-dimethyl-7,8-dihydro-6h-quinoline-5-ketone2-(3-bromo-phenylacetylene base)-7,7-dimethyl-7,8-dihydro-6h-quinoline-5-ketone3-(7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysene-quinoline-2-ethyl-acetylene base)-benzonitrile7,7-dimethyl-2-thiazole-5-ethyl-acetylene base-7,8-dihydro-6h-quinoline-5-ketone7,7-dimethyl-2- azoles-5-ethyl-acetylene base-7,8-dihydro-6h-quinoline-5-ketone2-(2-phenyl- azoles-5-ethyl-acetylene base)-7,8-dihydro-6h-quinoline-5-ketone or2-(2-phenyl-thiazole-5-ethyl-acetylene base)-7,8-dihydro-6h-quinoline-5-ketone;with its optical isomeric compound, pharmacy acceptable salt, hydrate, solvate and polymorph.
테트라히드로퀴놀리논 및 향대사성 글루타메이트 수용체의조절제로서의 이들의 용도본 발명은 에티닐-치환된 테트라히드로퀴놀리논 유도체 및 그의 제약상 허용되는 염에 관한 것이다. 추가로, 본 발명은 상기 화합물의 제조 방법에 관한 것이다. 본 발명의 화합물은 제I군 mGluR 조절제이며, 따라서 급성 및/또는 만성 신경계 장애의 제어 및 예방에 유용하다.하기 화학식 I의 화합물 또는 그의 광학 이성질체, 제약상 허용되는 염, 수화물, 용매화물 또는 다형체. <화학식 I> [이미지] 식 중, R1은 아릴 또는 헤테로아릴을 나타내고; R2 및 R3은 동일하거나 상이할 수 있으며, 수소 또는 C1-6알킬을 나타내고; R4 및 R5는 동일하거나 상이할 수 있으며, 수소 또는 C1-6알킬을 나타내고; 여기서, 아릴은 비치환된 페닐 고리, 또는 하나 이상의 불소, 염소 또는 브롬 원자로 임의로 치환된 C1-6알킬, 하나 이상의 불소, 염소 또는 브롬 원자로 임의로 치환된 C1-6알콕시, 시클로C3-12알킬, 히드록실, F, Cl, Br, I, CN, 니트로, 디-C1-6알킬아미노, N-시클로C3-12알킬-N-C1-6알킬아미노, 아제티디닐, 피롤리디닐, 피페리디닐, 모르폴리닐, 4-C1-6알킬-피페라지닐, 테트라졸릴, 옥사졸릴, 푸릴, 피롤릴, 티오페닐, 이속사졸릴, 티아졸릴, 이미다졸릴, 옥사디아졸릴, 피리디닐, 피리미딜 및 페닐로 이루어진 군으로부터 선택되는 동일하거나 상이할 수 있는 1개, 2개, 3개, 4개 또는 5개의 치환기로 치환된 페닐 고리를 나타내며; 헤테로아릴은 산소, 질소 및 황으로부터 독립적으로 선택되는 1개 내지 4개의 헤테로원자를 갖는 (헤테로)방향족 5원, 6원 또는 7원 고리를 나타내고, 여기서 상기 고리는 비치환되거나, 또는 하나 이상의 불소, 염소 또는 브롬 원자로 임의로 치환된 C1-6알킬, 하나 이상의 불소, 염소 또는 브롬 원자로 임의로 치환된 C1-6알콕시, 시클로C3-12알킬, 히드록실, F, Cl, Br, I, CN, 니트로, 디-C1-6알킬아미노, N-시클로C3-12알킬-N-C1-6알킬아미노, 아제티디닐, 피롤리디닐, 피페리디닐, 모르폴리닐, 4-C1-6알킬-피페라지닐, 테트라졸릴, 옥사졸릴, 푸릴, 피롤릴, 티오페닐, 이속사졸릴, 티아졸릴, 이미다졸릴, 옥사디아졸릴, 피리디닐, 피리미딜 및 페닐로 이루어진 군으로부터 선택되는 동일하거나 상이할 수 있는 1개, 2개 또는 3개의 치환기로 치환되고; 상기 화학식 I의 화합물은 2-페닐에티닐-7,8-디히드로-6H-퀴놀린-5-온 2-피리딘-3-일에티닐-7,8-디히드로-6H-퀴놀린-5-온 2-m-톨릴에티닐-7,8-디히드로-6H-퀴놀린-5-온 2-(3-히드록시-페닐에티닐)-7,8-디히드로-6H-퀴놀린-5-온 2-(3-메톡시-페닐에티닐)-7,8-디히드로-6H-퀴놀린-5-온 2-(3-플루오로-페닐에티닐)-7,8-디히드로-6H-퀴놀린-5-온 2-(3-클로로-페닐에티닐)-7,8-디히드로-6H-퀴놀린-5-온 2-(3-브로모-페닐에티닐)-7,8-디히드로-6H-퀴놀린-5-온 3-(5-옥소-5,6,7,8-테트라히드로-퀴놀린-2-일에티닐)-벤조니트릴 2-티아졸-5-일에티닐-7,8-디히드로-6H-퀴놀린-5-온 2-옥사졸-5-일에티닐-7,8-디히드로-6H-퀴놀린-5-온 7,7-디메틸-2-피리딘-3-일에티닐-7,8-디히드로-6H-퀴놀린-5-온 7,7-디메틸-2-m-톨릴에티닐-7,8-디히드로-6H-퀴놀린-5-온 2-(3-히드록시-페닐에티닐)-7,7-디메틸-7,8-디히드로-6H-퀴놀린-5-온 2-(3-메톡시-페닐에티닐)-7,7-디메틸-7,8-디히드로-6H-퀴놀린-5-온 2-(3-플루오로-페닐에티닐)-7,7-디메틸-7,8-디히드로-6H-퀴놀린-5-온 2-(3-클로로-페닐에티닐)-7,7-디메틸-7,8-디히드로-6H-퀴놀린-5-온 2-(3-브로모-페닐에티닐)-7,7-디메틸-7,8-디히드로-6H-퀴놀린-5-온 3-(7,7-디메틸-5-옥소-5,6,7,8-테트라히드로-퀴놀린-2-일에티닐)-벤조니트릴 7,7-디메틸-2-티아졸-5-일에티닐-7,8-디히드로-6H-퀴놀린-5-온 7,7-디메틸-2-옥사졸-5-일에티닐-7,8-디히드로-6H-퀴놀린-5-온 2-(2-페닐-옥사졸-5-일에티닐)-7,8-디히드로-6H-퀴놀린-5-온 또는 2-(2-페닐-티아졸-5-일에티닐)-7,8-디히드로-6H-퀴놀린-5-온을 나타내지 않을 수 있다.