PHARMACEUTICAL COMPOSITION COMPRISING A PYRAZOLE-O-GLUCOSIDE DERIVATIVEThe invention relates to a pharmaceutical composition comprising a pyrazole-O-glucoside derivative selected from the group of compounds (1) to (29) according to claim 1 in combination with at least one second therapeutic agent which is suitable in the treatment or prevention of one or more conditions selected from type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance and hyperglycemia. In addition the present invention relates to methods for preventing or treating of metabolic disorders and related conditions.A pharmaceutical composition comprising a pyrazole-O-glucoside derivative selected from the group of compounds (1) to (29) consisting of (1) 4-(2,3-difluoro-4-methoxy-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (2) 4-(2,5-difluoro-4-methoxy-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (3) 4-(2,6-difluoro-4-methoxy-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (4) 4-(3,5-difluoro-4-methoxy-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (5) 1-cyclobutyl-4-(3-fluoro-4-methyl-benzyl)-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (6) 1-cyclopropylmethyl-4-(3-fluoro-4-methyl-benzyl)-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (7) 1-cyclobutyl-4-(2-fluoro-4-methoxy-benzyl)-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (8) 4-(3-chloro-4-methoxy-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (9) 4-(2-chloro-4-methoxy-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (10) 4-(4-bromo-3-fluoro-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (11) 4-(2,3-difluoro-4-methyl-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (12) 4-(2-fluoro-4-methyl-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (13) 4-(3-fluoro-4-ethoxy-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (14) 4-(4-ethinyl-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (15) 4-(3-fluoro-4-isopropoxy-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (16) 4-(2-fluoro-4-methoxy-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (17) 4-(2-fluoro-4-methoxy-benzyl)-1-isopropyl-5-trifluoromethyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (18) 4-(4-bromo-2-fluoro-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (19) 4-(2-fluoro-4-isopropoxy-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (20) 4-(2-fluoro-4-ethoxy-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (21) 4-(4-ethyl-benzyl)-1-isopropyl-5-trifluoromethyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (22) 4-(4-bromo-benzyl)-1-isopropyl-5-trifluoromethyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (23) 4-(4-ethyl-benzyl)-1-cyclobutyl-5-trifluoromethyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (24) 4-(4-ethyl-benzyl)-1-(2-fluoro-1-fluoromethyl-ethyl)-5-trifluoromethyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (25) 4-(3-fluoro-4-methoxy-benzyl)-1-isopropyl-5-trifluoromethyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (26) 4-(3-fluoro-4-methyl-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (27) 4-(2,3-difluoro-4-isopropoxy-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (28) 4-(3-fluoro-4-methoxy-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; (29) 4-(4-ethyl-benzyl)-1-isopropyl-5-methyl-3-β-D-glucopyranos-1-yloxy-1H-pyrazole; or a prodrug thereof wherein one or more hydroxyl groups of the β-D-glucopyranosyl group are acylated with groups selected from (C1-3-alkyl)carbonyl, (C1-6-alkyl)-oxycarbonyl, phenylcarbonyl, phenyl-(C1-3-alkyl)-carbonyl, phenyloxycarbonyl and phenyl-(C1-3-alkyl)-oxycarbonyl, or a pharmaceutically acceptable salt thereof; in combination with at least one second therapeutic agent which is suitable in the treatment or prevention of one or more conditions selected from type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance (IGT), impaired fasting blood glucose (IFG), and hyperglycemia.
피라졸-Ｏ-글리코사이드 유도체를 포함하는 약제학적 조성물본 발명은, 청구항 제1항에 따르는 화합물 (1) 내지 (29)로 이루어진 그룹으로부터 선택된 피라졸-O-글리코사이드 유도체를, 1형 진성 당뇨병, 2형 진성 당뇨병, 내당능장애 및 과혈당증으로부터 선택되는 하나 이상의 상태의 치료 또는 예방에 적합한 하나 이상의 제2 치료제와 병용하여 포함하는 약제학적 조성물에 관한 것이다. 또한, 본 발명은 대사 장애 및 관련 상태를 예방 또는 치료하는 방법에 관한 것이다. (1) 4-(2,3-디플루오로-4-메톡시-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (2) 4-(2,5-디플루오로-4-메톡시-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (3) 4-(2,6-디플루오로-4-메톡시-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (4) 4-(3,5-디플루오로-4-메톡시-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (5) 1-사이클로부틸-4-(3-플루오로-4-메틸-벤질)-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (6) 1-사이클로프로필메틸-4-(3-플루오로-4-메틸-벤질)-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (7) 1-사이클로부틸-4-(2-플루오로-4-메톡시-벤질)-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (8) 4-(3-클로로-4-메톡시-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (9) 4-(2-클로로-4-메톡시-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (10) 4-(4-브로모-3-플루오로-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (11) 4-(2,3-디플루오로-4-메틸-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (12) 4-(2-플루오로-4-메틸-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (13) 4-(3-플루오로-4-에톡시-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (14) 4-(4-에티닐-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (15) 4-(3-플루오로-4-이소프로폭시-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (16) 4-(2-플루오로-4-메톡시-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (17) 4-(2-플루오로-4-메톡시-벤질)-1-이소프로필-5-트리플루오로메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (18) 4-(4-브로모-2-플루오로-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (19) 4-(2-플루오로-4-이소프로폭시-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (20) 4-(2-플루오로-4-에톡시-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (21) 4-(4-에틸-벤질)-1-이소프로필-5-트리플루오로메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (22) 4-(4-브로모-벤질)-1-이소프로필-5-트리플루오로메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (23) 4-(4-에틸-벤질)-1-사이클로부틸-5-트리플루오로메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (24) 4-(4-에틸-벤질)-1-(2-플루오로-1-플루오로메틸-에틸)-5-트리플루오로메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (25) 4-(3-플루오로-4-메톡시-벤질)-1-이소프로필-5-트리플루오로메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (26) 4-(3-플루오로-4-메틸-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (27) 4-(2,3-디플루오로-4-이소프로폭시-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (28) 4-(3-플루오로-4-메톡시-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸; (29) 4-(4-에틸-벤질)-1-이소프로필-5-메틸-3-ß-D-글루코피라노스-1-일옥시-1H-피라졸로 이루어진 화합물 (1) 내지 (29)의 그룹으로부터 선택되는 피라졸-O-글리코사이드 유도체 또는 이들의 프로드러그(여기서, β-D-글루코피라노실 그룹의 하나 이상의 하이드록실 그룹은 (C1-3-알킬)카보닐, (C1-6-알킬)옥시카보닐, 페닐카보닐, 페닐-(C1-3-알킬)-카보닐, 페닐옥시카보닐 및 페닐-(C1-3-알킬)-옥시카보닐로부터 선택된 그룹으로 아실화되어 있다) 또는 이들의 약제학적으로 허용되는 염을, 1형 진성 당뇨병, 2형 진성 당뇨병, 내당능장애(IGT), 공복혈당장애(IFG) 및 과혈당증으로부터 선택되는 하나 이상의 상태를 치료 또는 예방하기에 적합한 하나 이상의 제2 치료제와 병용하여 포함하는 약제학적 조성물.