公开(公告)号：EP1053227B1

公开(公告)日：2008-11-05

申请号：EP99901492.1

申请日：1999-01-20

申请人： AMGEN INC.

发明人： DE LA BROUSE-ELWOOD, Fabienne ,  JAEN, Juan, C. ,  MCGEE, Lawrence, R. ,  MIAO, Shi-Chang ,  RUBENSTEIN, Steven, Marc ,  CHEN, Jin-Long ,  CUSHING, Timothy, D. ,  FLYGARE, John, A. ,  HOUZE, Jonathan, B. ,  KEARNEY, Patrick, C.

IPC分类号： C07D213/65 ,  A61K31/435 ,  C07D239/34 ,  C07D213/643 ,  C07D233/70 ,  C07D413/12

CPC分类号： C07D213/70 ,  C07C311/21 ,  C07D213/65 ,  C07D215/20 ,  C07D217/04 ,  C07D405/12

摘要： Modulators of PPARη activity are provided having formula (I): in which the symbol Ar represents an aryl group; the letter X represents a divalent linkage selected from the group consisting of =C1-C6alkylene, -(C1-C6)alkylenoxy, -O-, -C(O)-, -N(R11)-, -N(R11)C(O)-, -S(O)¿k?- and a single bond, in which R?11¿ is a member selected from the group consisting of hydrogen, alkyl, heteroalkyl, and arylalkyl and the subscript k is an integer of from 0 to 2. The letter Y, in formula (I) represents a divalent linkage selected from the group consisting of alkylene, -O-, -C(O)-, -N(R12)-S(O)¿m?-, -N(R?13¿)-S(O)¿m-N(R?13)-, -N(R12)C(O)-, -S(O)¿n?-, a single bond, and combinations thereof in which R?12 and R13¿ are members independently selected from the group consisting of hydrogen, alkyl, heteroalkyl and arylalkyl; and the subscripts m and n independently integers of from 0 to 2. The symbol R1 represents a member selected from the group consisting of hydrogen, alkyl, heteroalkyl, aryl, arylalkyl, -CO¿2R?14, -CO(R)14, -C(O)NR15R16, -S(O)¿p-R?14, -S(O)¿q?-NR?15R16¿, -O-C(O)-OR17, -O-C(O)-R17, -O-C(O)-NR?15R16, -N(R14¿)-C(O)-NR?15R16, -N(R14¿)-C(O)-R17 and -N(R14)-C(O)-OR17, in which R14 is a member selected from the group consisting of hydrogen, alkyl, heteroalkyl, aryl and arylalkyl, and R?15 and R16¿ are members independently selected from the group consisting of hydrogen, alkyl, heteroalkyl, aryl and arylalkyl, or taken together with the nitrogen to which each is attached from a 5-, 6- or 7-membered ring. The symbol R17 represents a member selected from the group consisting of alkyl, heteroalkyl, aryl and arylalkyl. Additionally, for the R1 groups described above, the subscript p is an integer of from 0 to 3, and the subscript q is an integer of from 1 to 2. The symbol R2 represents a member selected from the group consisting of alkyl, heteroalkyl, aryl and arylalkyl. In another aspect, the present invention provides compounds of formula (I), as well as pharmaceutical compositions containing the compounds described above for the treatment of conditions such as type II diabetes and obesity.