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。

公开(公告)号：EP0934257A1

公开(公告)日：1999-08-11

申请号：EP97936050.0

申请日：1997-07-16

申请人： AMERICAN HOME PRODUCTS CORPORATION

发明人： ANTANE, Madelene, Miyoko ,  HERBST, David, Richard ,  McFARLANE, Geraldine, Ruth ,  GUNDERSEN, Eric, Gould ,  HIRTH, Bradford, Hammond ,  QUAGLIATO, Dominick, Anthony ,  GRACEFFA, Russell, Francis ,  BUTERA, John, Anthony ,  GILBERT, Adam, Matthew

IPC分类号： A61K31 ,  A61P9 ,  C07C221 ,  C07C225 ,  C07C233 ,  C07C255 ,  C07C271

CPC分类号： C07C225/20 ,  C07C233/41 ,  C07C255/58 ,  C07C271/24 ,  C07C2601/04 ,  C07C2601/08

摘要： The compounds of formula (I) wherein R1, R2, R3 and A are as defined herein are useful, via potassium channel modulation, in the treatment of disorders associated with smooth muscle contraction. Such disorders include, but are not limited to, urinary incontinence, hypertension, asthma, premature labor, irritable bowel syndrome, congestive heart failure, angina and cerebral vascular disease.

摘要翻译： 下式的化合物：其中R 1，R 2，R 3和A如本文所定义，通过钾通道调节可用于治疗与平滑肌收缩相关的疾病。 这些疾病包括但不限于尿失禁，高血压，哮喘，早产，肠易激综合征，充血性心力衰竭，心绞痛和脑血管疾病。