Azolidinecarbonitriles and their use as DPP-IV inhibitorsThe invention discloses a novel heterocyclic compounds that falls within f the ambit of general formula (I), its stereoisomers, pharmaceutically acceptable salts or solvates wherein X, n,k,z, R1, R2, R3, R4, R5 and R6 are as defined in the specification that are useful in (i) normalizing elevated blood pglucose levels in diabetes, (ii) treating disorders related to glucose intolerance and (iii) for scavenging free radicals of mammals. The invention also discloses pharmaceutically acceptable composition comprising these compounds, method for preparation of the compounds as defined bove and method of treating mammals including human beings by administering an effective amount of said compounds to a subject in need thereof. The invention further discloses use of these compounds in the manufacture of a medicament useful for treatment of different disease conditions as stated above.One kind is selected from down the heterogeneous ring compound of organizing, its steric isomer or its pharmaceutically acceptable solvate or salt:a) 3-[1-oxo-2-(1-(1-(2-oxo-2-(5-chloro-pyridine-2-yl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl (s)-(+)-4-cyano-tetrahydrothiazole, three-trifluoroacetateb) 3-[1-oxo-2-(1-(1-(2-oxo-2-(5-bromethiazole-2-yl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, three-trifluoroacetatec) 3-[1-oxo-2-(1-(1-(2-oxo-2-amino) ethyl) piperidin-4-yl)] diazanyl] ethyl-4-cyano-tetrahydrothiazole, two-trifluoroacetated) 3-[1-oxo-2-(1-(1-(2-oxo-2-(4,5-dimethylthiazole-2-yl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, three-trifluoroacetatee) 3-[1-oxo-2-(1-(1-(2-oxo-2 (5-cyanopyridine-2-yl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, three-trifluoroacetatef) 3-[1-oxo-2-(1-(1-(2-oxo-2-(2-chloro-pyridine base-3-yl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, three-trifluoroacetateg) 3-[1-oxo-2-(1-(1-(2-oxo-2-(2-luorobenzyl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, two-trifluoroacetateh) 3-[1-oxo-2-(1-(1-phenoxy group ethyl) piperidin-4-yl) diazanyl] ethyl-4-cyano group-thiazolidine, two-trifluoroacetatei) 3-[1-oxo-2-(1-(1-(2-oxo-2-(5-chloro-pyridine-2-yl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-2-cyanopyrolidine, three-trifluoroacetatej) 3-[1-oxo-2-(1-(1-(2-oxo-2-cyclohexyl) amino-ethyl) piperidin-4-yl) diazanyl] ethyl-4-cyano-tetrahydrothiazole, two-trifluoroacetatek) ethyl-4-cyano-tetrahydrothiazole 3-[(1-oxo-2-(1-(1-(2-oxo-2-(3-isopropoxy third-1-yl) amino-ethyl) piperidin-4-yl)) diazanyl), two-trifluoroacetatel) 3-[1-oxo-2-(1-(1-(2-oxo-2-(2-(thiophene-2-yl) ethyl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, two-trifluoroacetatem) 3-[1-oxo-2-(1-(1-(2-oxo-2-(3-chloro-4-fluoro-phenyl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, two-trifluoroacetaten) 3-[1-oxo-2-(1-(1-(2-oxo-2-(4-ethoxy carbonyl methylthiazol-2-yl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, three-trifluoroacetateo) 3-[1-oxo-2-(1-(1-(2-oxo-2-(3, the 4-methylenedioxyphenyl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, two-trifluoroacetatep) 3-[1-oxo-2-(1-(1-(2-oxo-2-(4-amino-sulfonyl phenyl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, two-trifluoroacetateq) 3-[1-oxo-2-(1-(1-(3-oxo-3-cyclopropyl) aminopropyl) piperidin-4-yl)] diazanyl] ethyl-4-cyano-tetrahydrothiazole, two-trifluoroacetater) 3-[1-oxo-2-(1-(1-(2-oxo-2-(5-chloro-pyridine-2-yl) amino-ethyl) piperidin-4-yl)-2-methoxycarbonyl) diazanyl] ethyl-4-cyano-tetrahydrothiazole, tri hydrochlorides) 3-[1-oxo-2-(1-(1-(2-oxo-2-(thiazol-2-yl)-amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, three-trifluoroacetatet) 3-[1-oxo-2-(1-(1-(2-oxo-2-(2-methoxy ethyl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, two-trifluoroacetateu) 3-[1-oxo-2-(1-(1-(2-oxo-2-(pyridine-2-yl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, three-trifluoroacetatev) 3-[1-oxo-2-(1-(1-(3-pyridyl ethanoyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, two-trifluoroacetatew) 3-[1-oxo-2-(1-(1-(2-oxo-2-(benzothiazole-2-yl) piperidin-4-yl)) diazanyl) ethyl-4-cyano-tetrahydrothiazole, three-trifluoroacetatex) 3-[1-oxo-2-(1-(1-(5-methylpyrazine-2-base carbonyl) amino-4-cyclohexyl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, three-trifluoroacetatey) 3-[1-oxo-2-(1-(1-(2-oxo-2-(5-cyanopyridine-2-yl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, tri hydrochloridez) 3-[1-oxo-2-(1-(1-(2-oxo-2-(2-chloro-pyridine-3-yl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, tri hydrochlorideaa) 3-[1-oxo-2-(1-(1-(2-oxo-2-(4-amino-sulfonyl phenyl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, dihydrochloridebb) 3-[1-oxo-2-(1-(1-(2-oxo-2-(4-chloro-phenyl-) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, dihydrochloridecc) 3-[1-oxo-2-(1-(1-(2-oxo-2-(benzothiazole-2-yl) amino-ethyl) piperidin-4-yl)) hydrazine] ethyl-4-cyano-tetrahydrothiazole, tri hydrochloridedd) 3-[1-oxo-2-(1-(1-(2-(4,5-dimethylthiazole-2-yl) amino-ethyl) piperidin-4-yl)) diazanyl] ethyl-4-cyano-tetrahydrothiazole, tri hydrochlorideee) 3-[1-oxo-2-(1-(1-(2-cyclopropyl-1-yl) amino-ethyl) piperidin-4-yl)] diazanyl] ethyl-4-cyano-tetrahydrothiazole, dihydrochlorideff) 3-[-oxo-2-(2-tert-butoxycarbonyl) diazanyl] ethyl-4-qing ji oxazolidine.
아졸리딘카르보니트릴 및 ＤＰＰ-Ⅳ 억제제로서의 이의용도본 발명은 일반식 (I)의 범위 내에 속하는 새로운 헤테로고리 화합물, 이의 입체이성질체, 약제학적으로 허용가능한 염 또는 용매화합물에 관한 것이다.  상기 식에서, X, n, k, z, R1, R2, R3, R4, R5 및 R6는 상세한 설명에서 정의한 바와 같으며, 이들 화합물은 (i)당뇨병에서 증가된 혈당 수치의 정상화, (ⅱ) 내당능장애와 관련된 질환의 치료 및 (ⅲ)포유동물의 자유 라디칼 제거에 유용하다. 또한, 본 발명은 이들 화합물을 포함하는 약제학적으로 허용가능한 조성물, 방법, 상기 정의한 화합물을 제조하는 방법 및 이들 화합물의 유효량을 이를 필요로하는 개체에게 투여함으로써 인간을 포함하는 포유동물을 치료하는 방법에 관한 것이다. 추가로, 본 발명은 상기 언급한 다른 질병 상태의 치료에 유용한 약제의 제조에 있어서 이들 화합물의 용도에 관한 것이다. 다음으로 이루어진 군에서 선택되는 헤테로고리 화합물, 이들의 입체이성질체 또는 이들의 약제학적으로 허용가능한 용매화합물 또는 염: a) 3-[1-옥소-2-(1-(1-(2-옥소-2-(5-클로로피리딘-2-일)아미노에틸)피페리딘-4-일))히드라지노]에틸(s)-(+)-4-시아노티아졸리딘 트리스-트리플루오로아세테이트. b) 3-[1-옥소-2-(1-(1-(2-옥소-2-(5-브로모티아졸-2-일)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 트리스-트리플루오로아세테이트. c) 3-[l-옥소-2-(l-(l-(2-옥소-2-아미노)에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 비스-트리플루오로아세테이트. d) 3-[1-옥소-2-(1-(1-(2-옥소-2-(4,5-디메틸티아졸-2-일)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 트리스-트리플루오로아세테이트. e) 3-[1-옥소-2-(1-(1-(2-옥소-2(5-시아노피리딘-2-일)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 트리스-트리플루오로아세테이트. f) 3-[1-옥소-2-(-1-(-1-(2-옥소-2-(2-클로로피리딜-3-일)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 트리스-트리플루오로아세테이트. g) 3-[1-옥소-2-(1-(1-(2-옥소-2-(2-플루오로벤질)아미노에틸)피페리딘-4- 일))히드라지노]에틸-4-시아노티아졸리딘, 비스-트리플루오로아세테이트. h) 3-[1-옥소-2-(1-(1-페녹시에틸)피페리딘-4-일)히드라지노]에틸-4-시아노-티아졸리딘, 비스-트리플루오로아세테이트. i) 3-[1-옥소-2-(1-(1-(2-옥소-2-(5-클로로피리딘-2-일)아미노에틸)피페리딘-4-일))히드라지노]에틸-2-시아노피롤리딘, 트리스-트리플루오로아세테이트. j) 3-[1-옥소-2-(1-(1-(2-옥소-2-시클로헥실)아미노에틸)피페리딘-4-일)히드라지노]에틸-4-시아노티아졸린, 비스-트리플루오로아세테이트. k) 3-[(1-옥소-2-(1-(1-(2-옥소-2-(3-이소프로폭시프로판-1-일)아미노에틸) 피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 비스-트리플루오로아세테이트. 1) 3-[l-옥소-2-(l-(l-(2-옥소-2-(2-(티오펜-2-일)에틸아미노에틸)피페리딘- 4-일))히드라지노]에틸-4-시아노티아졸리딘, 비스-트리플루오로아세테이트. m) 3-[1-옥소-2-(1-(1-(2-옥소-2-(3-클로로-4-플로오로-페닐)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 비스-트리플루오로아세테이트. n) 3-[1-옥소-2-(1-(1-(2-옥소-2-(4-에톡시카보닐메틸티아졸-2-일)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 트리스-트리플루오로아세테이트. o) 3-[1-옥소-2-(1-(1-(2-옥소-2-(3,4-메틸렌디옥시페닐)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 비스-트리플루오로아세테이트. p) 3-[l-옥소-2-(l-(l-(2-옥소-2-(4-아미노술포닐페닐)아미노에틸)피페리딘-4-일))히드라지노에틸-4-시아노티아졸리딘, 비스-트리플루오로아세테이트. q) 3-[1-옥소-2-(1-(1-(3-옥소-3-시클로프로필)아미노프로필)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 비스-트리플루오로아세테이트. r) 3-[1-옥소-2-(1-(1-(2-옥소-2-(5-클로로피리딘-2-일)아미노에틸)피페리딘-4-일)-2-메톡시카보닐)히드라지노]에틸-4-시아노티아졸리딘, 트리히드로클로라이드. s) 3-[1-옥소-2-(1-(1-(2-옥소-2-(티아졸-2-일)-아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 트리스-트리플루오로아세테이트. t) 3-[l-옥소-2-(l-(l-(2-옥소-2-(2-메톡시에틸)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 비스-트리플루오로아세테이트. u) 3-[1-옥소-2-(1-(1-(2-옥소-2-(피리딘-2-일)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 트리스-트리플루오로아세테이트. v) 3-[1-옥소-2-(1-(1-(3-피리딜아세틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 비스-트리플루오로아세테이트. w) 3-[l-옥소-2-(l-(l-(2-옥소-2-(벤조티아졸-2-일)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 트리스-트리플루오로아세테이트. x) 3-[1-옥소-2-(1-(1-(5-메틸피라진-2-일카보닐)아미노-4-시클로헥실))히드라지노]에틸-4-시아노티아졸리딘, 트리스-트리플루오로아세테이트. y) 3-[1-옥소-2-(1-(1-(2-옥소-2-(5-시아노피리딘-2-일)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 트리히드로클로라이드. z) 3-[1-옥소-2-(l-(l-(2-옥소-2-(2-클로로피리딘-3-일)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 트리히드로클로라이드. aa) 3-[1-옥소-2-(1-(1-(2-옥소-2-(4-아미노술포닐페닐)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 디히드로클로라이드. bb) 3-[1-옥소-2-(1-(1-(2-옥소-2-(4-클로로페닐)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 디히드로클로라이드. cc) 3-[1-옥소-2-(1-(1-(2-옥소-2-(벤조티아졸-2-일)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 트리히드로클로라이드. dd) 3-[1-옥소-2-(1-(1-(2-(4,5-디메틸티아졸-2-일)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 트리히드로클로라이드. ee) 3-[1-옥소-2-(1-(1-(2-시클로프로필-1-일)아미노에틸)피페리딘-4-일))히드라지노]에틸-4-시아노티아졸리딘, 디히드로클로라이드. 및 ff) 3-[-옥소-2-(2-ter-부틸옥시카보닐)히드라지노]에틸-4-시아노옥사졸리딘.