公开(公告)号：EP0891325B1

公开(公告)日：2002-02-06

申请号：EP97916852.3

申请日：1997-03-26

申请人： G.D. SEARLE & CO.

发明人： CHEN, Barbara, B. ,  CHEN, Helen, Y. ,  GESICKI, Glen, J. ,  HAACK, Richard, A. ,  MALECHA, James, W. ,  PENNING, Thomas, D. ,  RICO, Joseph, G. ,  ROGERS, Thomas, E. ,  RUMINSKI, Peter, G. ,  RUSSELL, Mark, A. ,  YU, Stella, S.

IPC分类号： C07C279/18 ,  A61K31/155 ,  C07D223/04 ,  C07C311/06 ,  C07C259/18 ,  C07C257/18 ,  C07C275/42 ,  C07C311/19 ,  C07C311/47 ,  C07D233/88 ,  C07C279/28

CPC分类号： C07D271/07 ,  A61K31/155 ,  C07C275/42 ,  C07C279/18 ,  C07C279/22 ,  C07C279/24 ,  C07C279/28 ,  C07C311/06 ,  C07C311/13 ,  C07C311/19 ,  C07C311/64 ,  C07C317/44 ,  C07C323/52 ,  C07D223/12 ,  C07D231/12 ,  C07D233/50 ,  C07D233/56 ,  C07D233/88 ,  C07D239/14 ,  C07D249/08 ,  C07D249/14 ,  C07D295/215

摘要： The present invention relates to a class of compounds represented by Formula (I) or a phramaceutically acceptable salt thereof, pharmaceutical composition comprising compounds of Formula (I), and methods of selectively inhibiting or antagonizing the αvβ3 integrin.

公开(公告)号：EP0772597B1

公开(公告)日：2001-12-12

申请号：EP95927154.5

申请日：1995-07-20

申请人： G.D. SEARLE & CO.

发明人： LEE, Len, F. ,  PENNING, Thomas, D. ,  KRAMER, Steven, W. ,  TALLEY, John, J.

IPC分类号： C07D231/12 ,  A61K31/415

CPC分类号： C07D231/12

摘要： A class of pyrazolyl compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by formula (II), wherein R1 is selected from alkyl, aralkyl, alkynyl, cyanoalkyl, carboxyalkyl, aminocarbonylalkyl, arylaminocarbonylalkyl, heterocyclicalkyl, and alkoxycarbonylalkyl; wherein R3 is aryl optionally substituted at a substitutable position with one or more radicals independently selected from halo, alkylthio, alkylsulfinyl, alkyl, cyano, carboxyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, N-alkyl-N-arylaminocarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino, heterocyclo and nitro; wherein R4 is haloalkyl; and wherein R5 is selected from alkyl and amino; or a pharmaceutically acceptable salt thereof.

公开(公告)号：EP0731796B1

公开(公告)日：2000-08-02

申请号：EP95902445.6

申请日：1994-11-14

申请人： G.D. SEARLE & CO.

发明人： TALLEY, John, J. ,  ROGIER, Donald, J., Jr. ,  PENNING, Thomas, D. ,  YU, Stella, S.

IPC分类号： C07D231/12 ,  C07D405/04 ,  C07D409/04 ,  A61K31/415

CPC分类号： C07D231/12 ,  C07D231/16 ,  C07D405/04 ,  C07D409/04

摘要： A class of 1,3,5-substituted pyrazoles is described for the treatment of inflammation, including treatment of pain and disorders such as arthritis. Compounds of particular interest are of formula (I) wherein R1 is lower alkylsulfonyl or sulfamyl; wherein R2 is aryl or heteroaryl; wherein R2 is optionally substituted at a substitutable position with one or more radicals selected from halo, lower alkoxy, lower alkyl, nitro, lower alkylthio, amino, lower haloalkyl, hydroxyl, carboxyl, N-monoalkylamino, N,N-dialkylamino, cyano, alkoxycarbonyl and acylamino; wherein R3 is selected from hydrido, lower alkyl, lower haloalkyl, cyano, carboxyl, alkoxycarbonyl, amino, acyl, acylamino, halo and alkylsulfonylamino; wherein R4 is aryl or heteroaryl; wherein R4 is optionally substituted at a substitutable postion with one or more radicals selected from halo, lower alkoxy, lower alkyl, nitro, lower alkylthio, amino, lower haloalkyl, hydroxyl, carboxyl, N-monoalkylamino, N,N-dialkylamino, cyano, alkoxycarbonyl and acylamino; provided at least one or R?2 and R4¿ cannot be phenyl or substituted triazole, when R1 is sulfamyl; further provided R2 cannot be 4-methoxyphenyl or 4-methylphenyl when R4 is 4-methoxyphenyl or 4-methylphenyl, and when R1 is sulfamyl; and further provided that R2 cannot be tetrazole when R4 is fluorophenyl, and when R1 is methylsulfonyl; or a pharmaceutically-acceptable salt thereof.

公开(公告)号：EP0731795B1

公开(公告)日：1999-12-22

申请号：EP95902444.9

申请日：1994-11-14

申请人： G.D. SEARLE & CO.

发明人： TALLEY, John, J. ,  PENNING, Thomas, D. ,  COLLINS, Paul, W. ,  ROGIER, Donald, J., Jr. ,  MALECHA, James, W. ,  MIYASHIRO, Julie M. ,  BERTENSHAW, Stephen, R. ,  KHANNA, Ish, K. ,  GRANETS, Matthew, J. ,  ROGERS, Roland, S. ,  CARTER, Jeffery, S. ,  DOCTER, Stephen, H. ,  YU, Stella, S.

IPC分类号： C07D231/12 ,  A61K31/415 ,  C07D231/14 ,  C07D231/16 ,  C07D231/18 ,  C07D231/54 ,  C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04 ,  C07D495/04

CPC分类号： C07D495/04 ,  C07D231/12 ,  C07D231/14 ,  C07D231/16 ,  C07D231/54 ,  C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04

摘要： A class of pyrazolyl benzenesulfonamide compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by formula (II), whrein R2 is selected from hydrido, alkyl, haloalkyl, alkoxycarbonyl, cyano, cyanoalkyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, cycloalkylaminocarbonyl, arylaminocarbonyl, carboxyalkylaminocarbonyl, carboxyalkyl, aralkoxycarbonylalkylaminocarbonyl, aminocarbonylalkyl, alkoxycarbonylcyanoalkenyl and hydroxyalkyl; wherein R3 is selected from hydrido, alkyl, cyano, hydroxyalkyl, cycloalkyl, alkylsulfonyl and halo; and wherein R4 is selected from aralkenyl, aryl, cycloalkyl, cycloalkenyl and heterocyclic; wherein R4 is optionally substituted at a substitutable position with one or more radicals selected from halo, alkylthio, alkylsulfonyl, cyano, nitro, haloalkyl, alkyl, hydroxyl, alkenyl, hydroxyalkyl, carboxyl, cycloalkyl, alkylamino, dialkylamino, alkoxycarbonyl, aminocarbonyl, alkoxy, haloalkoxy, sulfamyl, heterocyclic and amino; provided R?2 and R3¿ are not both hydrido; further provided that R2 is not carboxyl or methyl when R3 is hydrido and when R4 is phenyl; further provided that R4 is not triazolyl when R2 is methyl; further provided that R4 is not aralkenyl when R2 is carboxyl, aminocarbonyl or ethoxycarbonyl; further provided that R4 is not phenyl when R2 is methyl and R3 is carboxyl; and further provided that R4 is not unsubstituted thienyl when R2 is trifluoromethyl; or a pharmaceutically acceptable salt thereof.

公开(公告)号：EP0772597A1

公开(公告)日：1997-05-14

申请号：EP95927154.0

申请日：1995-07-20

申请人： G.D. SEARLE & CO.

发明人： LEE, Len, F. ,  PENNING, Thomas, D. ,  KRAMER, Steven, W. ,  TALLEY, John, J.

IPC分类号： A61K31 ,  A61P19 ,  A61P25 ,  A61P29 ,  C07D231 ,  C07D401 ,  C07D403

CPC分类号： C07D231/12

摘要： A class of pyrazolyl compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by formula (II), wherein R1 is selected from alkyl, aralkyl, alkynyl, cyanoalkyl, carboxyalkyl, aminocarbonylalkyl, arylaminocarbonylalkyl, heterocyclicalkyl, and alkoxycarbonylalkyl; wherein R3 is aryl optionally substituted at a substitutable position with one or more radicals independently selected from halo, alkylthio, alkylsulfinyl, alkyl, cyano, carboxyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, N-alkyl-N-arylaminocarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino, heterocyclo and nitro; wherein R4 is haloalkyl; and wherein R5 is selected from alkyl and amino; or a pharmaceutically acceptable salt thereof.

公开(公告)号：EP0731796A1

公开(公告)日：1996-09-18

申请号：EP95902445.0

申请日：1994-11-14

申请人： G.D. SEARLE & CO.

发明人： TALLEY, John, J. ,  ROGIER, Donald, J., Jr. ,  PENNING, Thomas, D. ,  YU, Stella, S.

IPC分类号： A61K31 ,  A61P25 ,  A61P29 ,  C07D231 ,  C07D401 ,  C07D405 ,  C07D409

CPC分类号： C07D231/12 ,  C07D231/16 ,  C07D405/04 ,  C07D409/04

摘要： A class of 1,3,5-substituted pyrazoles is described for the treatment of inflammation, including treatment of pain and disorders such as arthritis. Compounds of particular interest are of formula (I) wherein R1 is lower alkylsulfonyl or sulfamyl; wherein R2 is aryl or heteroaryl; wherein R2 is optionally substituted at a substitutable position with one or more radicals selected from halo, lower alkoxy, lower alkyl, nitro, lower alkylthio, amino, lower haloalkyl, hydroxyl, carboxyl, N-monoalkylamino, N,N-dialkylamino, cyano, alkoxycarbonyl and acylamino; wherein R3 is selected from hydrido, lower alkyl, lower haloalkyl, cyano, carboxyl, alkoxycarbonyl, amino, acyl, acylamino, halo and alkylsulfonylamino; wherein R4 is aryl or heteroaryl; wherein R4 is optionally substituted at a substitutable postion with one or more radicals selected from halo, lower alkoxy, lower alkyl, nitro, lower alkylthio, amino, lower haloalkyl, hydroxyl, carboxyl, N-monoalkylamino, N,N-dialkylamino, cyano, alkoxycarbonyl and acylamino; provided at least one or R?2 and R4¿ cannot be phenyl or substituted triazole, when R1 is sulfamyl; further provided R2 cannot be 4-methoxyphenyl or 4-methylphenyl when R4 is 4-methoxyphenyl or 4-methylphenyl, and when R1 is sulfamyl; and further provided that R2 cannot be tetrazole when R4 is fluorophenyl, and when R1 is methylsulfonyl; or a pharmaceutically-acceptable salt thereof.