Pyrazole derivatives which modulate stearoyl-coa desaturaseThe present invention provides heterocyclic derivatives that modulate the activity of stearoyl-CoA desaturase. Methods of using such derivatives to modulate the activity of stearoyl-CoA desaturase and pharmaceutical compositions comprising such derivatives are also encompassed.The compound of formula (i) or its pharmacy acceptable salt:whereinq isw is-n (r 8) c (o)-,-c (o) n (r 8)-, c 1-c 6alkylidene group, c 2-c 8alkenylene, c 2-c 6alkynylene or direct bond; v is selected from c 1-c 6alkylidene group; n is 1,2 or 3;p is 0,1,2,3,4,5 or 6;r 1be hydrogen, optional substituted c 1-c 7alkyl, c 2-c 6thiazolinyl, c 2-c 6alkynyl, c 1-c 7alkoxyl group, hydroxyl c 1-c 4alkyl, c 1-c 7alkoxy c 1-c 4alkyl, optional substituted c 3-c 7naphthenic base, optional substituted c 3-c 7naphthenic base c 1-c 4alkyl, optional substituted c 6-c 10aryl, halo c 1-c 4alkyl, optional substituted c 6-c 10aryl c 1-c 4alkyl, optional substituted c 2-c 10heterocyclic radical, optional substituted c 2-c 10heterocyclic radical c 1-c 4alkyl, optional substituted c 1-c 10heteroaryl or optional substituted c 1-c 10heteroaryl c 1-c 4alkyl; r 2be c 3-c 7alkyl, c 2-c 6thiazolinyl, c 2-c 6alkynyl, c 1-c 7alkoxyl group, hydroxyl, hydroxyl c 1-c 4alkyl, halo c 1-c 4alkyl, c 1-c 6alkoxy c 1-c 4alkyl, optional substituted c 3-c 7naphthenic base, optional substituted c 6-c 10aryl, optional substituted c 2-c 10heterocyclic radical or and optional substituted c 1-c 10heteroaryl, condition are to work as r 1when being alkyl, v-r 2it or not the quinolyl-4 methyl; r 3be hydrogen, c 1-c 8alkyl, c 2-c 8thiazolinyl, c 2-c 6alkynyl, c 1-c 6alkoxyl group, hydroxyl c 1-c 4alkyl, c 1-c 6alkoxy c 1-c 4alkyl, c 3-c 7naphthenic base, c 3-c 7naphthenic base c 1-c 4alkyl, c 2-c 10heterocyclic radical, c 6-c 10aryl, c 8-c 10aryl c 1-c 4alkyl, c 1-c 10heteroaryl, halogen, halo c 1-c 4alkyl, trifluoromethoxy, cyanic acid, hydroxyl or-n (r 8) 2r 5and r 5abe independently selected from hydrogen, c 1-c 6alkyl, halo c 1-c 4alkyl, hydroxyl, hydroxyl c 1-c 4alkyl, c 1-c 8alkoxyl group, c 3-c 7naphthenic base c 1-c 4alkyl and c 6-c 10aryl c 1-c 4alkyl; perhaps r 5and r 5aform oxo (=o) group or form c together 3-c 7naphthenic base; r 6be independently selected from c when occurring at every turn 1-c 6alkyl, c 6-c 10aryl, c 3-c 7naphthenic base, c 1-c 10heteroaryl, c 2-c 10heterocyclic radical, hydroxyl c 1-c 4alkyl, halo c 1-c 4alkyl, c 1-c 6alkoxyl group, c 3-c 7naphthenic base c 1-c 4alkyl, c 6-c 10aryl c 1-c 4alkyl-n (r 8) c (o) r 12,-c (o) n (r 8) r 12,-oc (o) n (r 8) r 12,-n (r 8) c (o) or 12,-n (r 8) c (o) n (r 8) r 12,-or 12,-sr 12,-n (r 8) r 12,-s (o) tr 12,-n (r 8) s (o) 2r 12,-s (o) 2n (r 8) r 12,-os (o) 2n (r 8) r 12,-c (o) r 12,-oc (o) r 12,-n (r 8) c (=n (r 8a)) n (r 8) r 12,-n (r 8) c (=s) n (r 8) r 12,-n (r 8) ((r 8a) n=) cr 12with-c (=n (r 8a)) n (r 8) r 12the perhaps r on adjacent carbons 5and r 6form c together 3-c 7naphthenic base or c 6-c 10aryl; r 7be hydrogen, c 1-c 7alkyl, halo c 1-c 4alkyl, c 6-c 10aryl, c 3-c 7naphthenic base, c 1-c 10heteroaryl, c 2-c 10heterocyclic radical, hydroxyl c 1-c 4alkyl, c 3-c 7naphthenic base c 1-c 4alkyl or aralkyl; r 8be independently selected from hydrogen, c when occurring at every turn 1-c 7alkyl, hydroxyl c 1-c 4alkyl, c 3-c 7naphthenic base, c 3-c 7naphthenic base c 1-c 4alkyl, c 6-c 10aryl, c 1-c 10heteroaryl, c 2-c 10heterocyclic radical and aralkyl; and r 8abe independently selected from hydrogen, c when occurring at every turn 1-c 7alkyl, c 3-c 7naphthenic base, c 3-c 7naphthenic base c 1-c 4alkyl and cyanic acid; r 12be independently selected from hydrogen, c when occurring at every turn 3-c 7alkyl, c 2-c 6thiazolinyl, c 2-c 6alkynyl, c 1-c 7alkoxyl group, hydroxyl, hydroxyl c 1-c 4alkyl, c 1-c 8alkoxy c 1-c 4alkyl, c 3-c 7naphthenic base, c 3-c 7naphthenic base c 1-c 4alkyl, c 6-c 10aryl, halo c 1-c 4alkyl, aralkyl, aralkyl oxy, c 2-c 10heterocyclic radical, c 2-c 10heterocyclic radical c 1-c 4alkyl, c 1-c 10heteroaryl and c 1-c 10heteroaryl c 1-c 4alkyl.
스테아로일-ＣＯＡ 탈포화화효소를 조절하는 피라졸 유도체본 발명은 스테아로일-CoA 탈포화화효소의 활성을 조절하는 헤테로시클릭 유도체를 제공한다. 이러한 유도체를 사용하여 스테아로일-CoA 탈포화화효소의 활성을 조절하는 방법, 및 이러한 유도체를 포함하는 제약 조성물 또한 포함된다.하기 화학식 I의 화합물 또는 그의 제약상 허용되는 염.<화학식 I>[이미지]식 중,Q는 [이미지]이고;W는 -N(R8)C(O)-, -C(O)N(R8)-, C1-C6알킬렌, C2-C6알케닐렌, C2-C6알키닐렌 또는 직접 결합이고;V는 C1-C6알킬렌으로부터 선택되고;n은 1, 2 또는 3이고;p는 0, 1, 2, 3, 4, 5 또는 6이고;R1은 수소, 임의로 치환된 C1-C7알킬, C2-C6알케닐, C2-C6알키닐, C1-C7알콕시, 히드록시C1-C4알킬, C1-C7알콕시C1-C4알킬, 임의로 치환된 C3-C7시클로알킬, 임의로 치환된 C3-C7시클로알킬C1-C4알킬, 임의로 치환된 C6-C10아릴, 할로C1-C4알킬, 임의로 치환된 C6-C10아릴C1-C4알킬, 임의로 치환된 C2-C10헤테로시클릴, 임의로 치환된 C2-C10헤테로시클릴C1-C4알킬, 임의로 치환된 C1-C10헤테로아릴, 또는 임의로 치환된 C1-C10헤테로아릴C1-C4알킬이고;R2는 C3-C7알킬, C2-C6알케닐, C2-C6알키닐, C1-C7알콕시, 히드록시, 히드록시C1-C4알킬, 할로C1-C4알킬, C1-C6알콕시C1-C4알킬, 임의로 치환된 C3-C7시클로알킬, 임의로 치환된 C6-C10아릴, 임의로 치환된 C2-C10헤테로시클릴, 또는 임의로 치환된 C1-C10헤테로아릴이되, 단 R1이 알킬인 경우에 V-R2는 퀴놀린-4-일메틸이 아니고;R3은 수소, C1-C6알킬, C2-C6알케닐, C2-C6알키닐, C1-C6알콕시, 히드록시C1-C4알킬, C1-C6알콕시C1-C4알킬, C3-C7시클로알킬, C3-C7시클로알킬C1-C4알킬, C2-C10헤테로시클릴, C6-C10아릴, C6-C10아릴C1-C4알킬, C1-C10헤테로아릴, 할로, 할로C1-C4알킬, 트리플루오로메톡시, 시아노, 히드록시 또는 -N(R8)2이고;R5 및 R5a는 수소, C1-C6알킬, 할로C1-C4알킬, 히드록시, 히드록시C1-C4알킬, C1-C6알콕시, C3-C7시클로알킬C1-C4알킬 및 C6-C10아릴C1-C4알킬로부터 독립적으로 선택되거나; 또는R5 및 R5a는 함께 옥소 (=O) 기 또는 C3-C7시클로알킬을 형성하고;R6은 각 경우 C1-C6알킬, C6-C10아릴, C3-C7시클로알킬, C1-C10헤테로아릴, C2-C10헤테로시클릴, 히드록시C1-C4알킬, 할로C1-C4알킬, C1-C6알콕시, C3-C7시클로알킬C1-C4알킬, C6-C10아릴C1-C4알킬-N(R8)C(O)R12, -C(O)N(R8)R12, -OC(O)N(R8)R12, -N(R8)C(O)OR12, -N(R8)C(O)N(R8)R12, -OR12, -SR12, -N(R8)R12, -S(O)tR12, -N(R8)S(O)2R12, -S(O)2N(R8)R12, -OS(O)2N(R8)R12, -C(O)R12, -OC(O)R12, -N(R8)C(=N(R8a))N(R8)R12, -N(R8)C(=S)N(R8)R12, -N(R8)((R8a)N=)CR12 및 -C(=N(R8a))N(R8)R12로부터 독립적으로 선택되거나; 또는인접한 탄소 상의 R5 및 R6은 함께 C3-C7시클로알킬 또는 C6-C10아릴을 형성하고;R7은 수소, C1-C7알킬, 할로C1-C4알킬, C6-C10아릴, C3-C7시클로알킬, C1-C10헤테로아릴, C2-C10헤테로시클릴, 히드록시C1-C4알킬, C3-C7시클로알킬C1-C4알킬 또는 아르알킬이고;R8은 각 경우 수소, C1-C7알킬, 히드록시C1-C4알킬, C3-C7시클로알킬, C3-C7시클로알킬C1-C4알킬, C6-C10아릴, C1-C10헤테로아릴, C2-C10헤테로시클릴 및 아르알킬로부터 독립적으로 선택되고;R8a는 각 경우 수소, C1-C7알킬, C3-C7시클로알킬, C3-C7시클로알킬C1-C4알킬 및 시아노로부터 독립적으로 선택되고;R12는 각 경우 수소, C3-C7알킬, C2-C6알케닐, C2-C6알키닐, C1-C7알콕시, 히드록시, 히드록시C1-C4알킬, C1-C6알콕시C1-C4알킬, C3-C7시클로알킬, C3-C7시클로알킬C1-C4알킬, C6-C10아릴, 할로C1-C4알킬, 아르알킬, 아르알킬옥시, C2-C10헤테로시클릴, C2-C10헤테로시클릴C1-C4알킬, C1-C10헤테로아릴 및 C1-C10헤테로아릴C1-C4알킬로부터 독립적으로 선택된다.