公开(公告)号：EP1244628A1

公开(公告)日：2002-10-02

申请号：EP00986937.1

申请日：2000-12-20

申请人： MERCK FROSST CANADA INC.

发明人： DESCHENES, Denis ,  DUBE, Daniel ,  GALLANT, Michel ,  GIRARD, Yves ,  LACOMBE, Patrick ,  MACDONALD, Dwight ,  MASTRACCHIO, Anthony ,  PERRIER, Helene

IPC分类号： C07D215/12 ,  A61K31/47 ,  A61K31/4709 ,  C07D215/14 ,  C07D401/10 ,  C07D413/10 ,  C07D417/10

CPC分类号： C07D401/10 ,  C07D215/12 ,  C07D215/14 ,  C07D401/14 ,  C07D405/12 ,  C07D409/10 ,  C07D413/10 ,  C07D413/14 ,  C07D417/10 ,  C07D417/12 ,  C07D417/14

摘要： Novel substituted 8-arylquinolines represented by Formula (I), or a pharmaceutically acceptable salt thereof, wherein S1, S2 and S3 are independently H, -OH; halogen, -C1-C6alkyl, -NO2, -CN, or -C1-C6alkoxy, wherein the alkyl and alkoxy groups are optionally substituted with 1-5 substituents; wherein each substituent is independently a halogen or OH; R1 is a H, OH, halogen, carbonyl, or -C1-C6alkyl, -cycloC3-C6alkyl, -C1-C6alkenyl, -C1-C6alkoxy, aryl, heteroaryl, -CN, -heterocycloC3-C6alkyl, -amino, -C1-C6alkylamino, -(C1-C6alkyl)(C1-C6alkyl)amino, -C1-C6alkyl(oxy)C1-C6alkyl, -C(O)NH(aryl), -C(O)NH(heteroaryl), -SOnNH(aryl), -SOnNH(heteroaryl), -SOnNH(C1-C6alkyl), -C(O)N(C0-C6alkyl) (C0-C6alkyl), -NH-SOn-(C1-C6alkyl), -SOn-(C1-C6alkyl), -(C1-C6alkyl)-O-C(CN)-dialkylamino, or -(C1-C6alkyl)-SOn-(C1-C6alkal) group, wherein any of the groups is optionally substituted with 1-5 substituents; wherein each substituent is independently a halogen, -OH, -CN, -C1-C6alkyl, -cycloC3-C6alkyl, -C(O)(heterocycloC3-C6alkyl), -C(O)-O-(C0-C6alkyl), -C(O)-aryloxy, -C1-C6alkoxy, -(C0-C6alkyl)(C0-C6alkyl)amino, cycloalkyloxy, acyl, acyloxy, -cycloC3-C6alkyl, heterocycloC3-C6alkyl, aryl, heteroaryl, carbonyl, carbamoyl, or -SOn-(C1-C6alkyl); A is CH, C-ester, or C-R4; R2 and R3 independently is an aryl, heteroaryl, H, halogen, -CN, -C1-C6alkyl, heterocycloC3-6alkyl, -C1-C6alkoxy, carbonyl, carbamoyl, -C(O)OH, -C1-C6alkyl)-SOn-(C1-C6alkyl), -C(O)N(C0-C6alkyl)(C0-C6alkyl), or -C1-C6alkylacylamino group, wherein any of the groups is optionally substituted with 1-5 substituents, wherein each substituent is independently an aryl, heteroaryl, halogen, -NO2, -C(O)OH, carbonyl, -CN, -C1-C6alkyl, -SOn-(C1-C6alkyl), -SOn-(aryl), aryloxy, -heteroaryloxy, C1-C6alkoxy, N-oxide, -C(O)-heterocycloC3-C6alkyl, -NH-cycloC3-C6alkyl, amino, -OH, or -(C0-C6alkyl)(C0-C6alkyl)amino, -C(O)-N(C0-C6alkyl)(C0-C6alkyl) substituent group, wherein each substituent group independently is optionally substituted with -OH, C1-C6alkoxy, -C1-C6alkyl, -cycloC3-C6alkyl, aryloxy, -C(O)OH, -C(O)O(C1-C6alkyl), halogen, -NO2, -CN, -SOn-(C1-C6alkyl), or -C(O)-N(C0-C6alkyl)(C0-C6alkyl); one of R2 and R3 must be an aryl or heteroaryl, optionally substituted; when R2 and R3 are both an aryl or heteroaryl, then R2 and R3 may be optionally connected by a thio, oxy, or (C1-C4alkyl) bridge to form a fused three ring system; are PDE4 inhibitors.

公开(公告)号：EP1021429A1

公开(公告)日：2000-07-26

申请号：EP98947246.9

申请日：1998-10-01

申请人： MERCK FROSST CANADA INC.

发明人： PERRIER, Helene ,  HAN, Yongxin ,  BAYLY, Christopher ,  MacDONALD, Dwight ,  GIROUX, Andre ,  YOUNG, Robert, N.

IPC分类号： C07D307/42 ,  A61K31/34 ,  C07D307/38 ,  C07D307/46 ,  C07D307/54 ,  C07D307/56 ,  C07D307/64 ,  C07D307/66 ,  C07D473/38 ,  C07D405/04 ,  C07D405/12 ,  C07D417/12 ,  C07D413/12 ,  C07D405/06 ,  C07F7/08

CPC分类号： C07D307/42 ,  C07D307/46 ,  C07D307/54 ,  C07D405/04 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07F7/0814

摘要： The invention encompasses the novel compound of Formula (I) useful in the treatment of diseases, including asthma, by raising the level of cyclic adenosine-3',5'-monophosphate (cAMP) through the inhibition of phosphodiesterase IV (PDE IV). The invention also encompasses certain pharmaceutical compositions and methods for treatment of diseases by inhibition of PDE IV, resulting in an elevation of cAMP, comprising the use of compounds of Formula (I).