公开(公告)号：EP1077929A1

公开(公告)日：2001-02-28

申请号：EP99924158.1

申请日：1999-05-10

申请人： AMERICAN HOME PRODUCTS CORPORATION

发明人： BUTERA, John, Anthony ,  CAUFIELD, Craig, Eugene ,  GRACEFFA, Russell, Francis ,  GREENFIELD, Alexander ,  GUNDERSEN, Eric, Gould ,  HAVRAN, Lisa, Marie ,  KATZ, Alan, Howard ,  LENNOX, Joseph, Richard ,  MAYER, Scott, Christian ,  McDEVITT, Robert, Emmett

IPC分类号： C07C235/44 ,  C07C59/70 ,  C07D307/80 ,  C07F9/38 ,  C07F9/40 ,  A61K31/165 ,  A61K31/19

CPC分类号： C07F9/4006 ,  C07B2200/07 ,  C07C17/16 ,  C07C45/68 ,  C07C45/71 ,  C07C47/575 ,  C07C205/35 ,  C07C205/37 ,  C07C225/20 ,  C07C233/43 ,  C07C235/46 ,  C07C235/48 ,  C07C235/52 ,  C07C237/30 ,  C07C255/54 ,  C07C271/12 ,  C07C271/16 ,  C07C271/28 ,  C07C271/30 ,  C07C309/77 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07D209/08 ,  C07D213/40 ,  C07D233/54 ,  C07D263/58 ,  C07D295/088 ,  C07D295/13 ,  C07D307/58 ,  C07D307/80 ,  C07D307/81 ,  C07D317/54 ,  C07D333/74 ,  C07D413/12 ,  C07C22/04

摘要： This invention provides compounds of Formula (I) having structure (I) wherein: B and D are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, aryl, heteroaryl, aralkyl of 6-12 carbon atoms, or heteroaralkyl of 6-12 carbon atoms except where B and D both are hydrogen; R1 is hydrogen, alkyl of 1-6 carbon atoms, -SO¿2?Ph(OH)(CO2H), -CH(R?2¿)W, -CH¿2?CH2Y, or -CH2CH2CH2Y; R?2¿ is hydrogen, alkyl of 1-6 carbon atoms, aralkyl of 6-12 carbon atoms, -CH¿2?(1H-imidazol-4-yl), -CH2(3-1H-indolyl), -CH2CH2(1,3-dioxo-1,3-dihydro-isoindol-2-yl), -CH2CH2(1-oxo-1,3-dihydro-isoindol-2-yl), or -CH2(3-pyridyl); W is -CO2R?3¿, -CONHOH, -CN, -CONHR3, aryl, heteroaryl, -CHO, -CH=NOR3, or -CH=NHNHR3; Y is -W, -OCH¿2CO2R?3, aryl, heteroaryl, -C(=NOH)NH¿2, -OR?3, -O(C=O)NR?4R5, -NR3(C=O)OR3, -NR3(C=O)NR4R5¿, or -NR4R5; R3 is hydrogen or alkyl of 1-6 carbon atoms; R?4 and R5¿ are each, independently, hydrogen, or alkyl of 1-6 carbon atoms or R?4 and R5¿ are, together, -(CH¿2?)n-, or -CH2CH2XCH2CH2-; X is O, S, SO, SO2, NR?3¿, or CH¿2?; n is 2 to 5; C is alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, -CONR?6R7, -NR3CONR6R7, -NR3COR6, -OR6, -O¿2CNR?6R7, -NR3CO¿2R6, -O2CR6, -CH2OR?6, -NR6R7, -CR3=CR3R8¿, -CPh¿3?, -CH2NR?6R7¿, or Formula (1); R?6 and R7¿ are each, independently, hydrogen, alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, cycloalkyl of 3-10 carbon atoms, -(CH¿2?CH2O)nCH3, -(CH2)mA or R?6 and R7¿ are, together, -(CH¿2?)p-, -(CH2)2N(CH3)(CH2)4-, -(CH2)2N(R?8)(CH¿2)2-, or -(CH2)2CH(R8)-(CH2)2-; R8 is hydrogen, alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, cycloakyl or 3-10 carbon atoms, -(CH¿2?CH2O)nCH3, -(CH2CH2CH2O)nCH3, or -(CH2)mA; A is aryl, heteroaryl, aryloxy, heteroaryloxy, arylthio, heteroarylthio, arylsulfoxy, heteroarylsulfoxy, arylsulfonyl, heteroarylsulfonyl, -CHF2, -CH2F, -CF3, -(CH2CH2O)nCH3, -(CH2CH2CH2O)nCH3, -CO2R?3¿, -O(C=O)NR6R7, aralkyloxy, or heteroaralkyloxy; m is 2 to 16; p is 2 to 12; or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.

摘要翻译： 本发明提供具有结构的式I化合物，其中B，C，D和R 1如本说明书中所定义，或其药学上可接受的盐，其可用于治疗与胰岛素抵抗或高血糖相关的代谢紊乱。