公开(公告)号：EP0772600A1

公开(公告)日：1997-05-14

申请号：EP95928164.0

申请日：1995-07-27

申请人： G.D. SEARLE & CO.

发明人： KHANNA, Ish, K. ,  WEIER, Richard, M. ,  COLLINS, Paul, W. ,  YU, Yi ,  XU, Xiangdong ,  HUFF, Renee, M. ,  PARTIS, Richard, A. ,  KOSZYK, Francis, J.

IPC分类号： C07D233 ,  A61K31 ,  A61P25 ,  A61P29 ,  A61P43 ,  C07D401 ,  C07D403 ,  C07D405 ,  C07D409 ,  C07D419

CPC分类号： C07D233/64 ,  C07D233/32 ,  C07D233/90 ,  C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04 ,  C07D419/04

摘要： A class of imidazolyl compounds is described for use in treating inflammation. Compounds of particular interest are defined by formula (II), wherein R3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, acyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkyloxy, cycloalkyloxyalkyle, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cyanoalkyl, cycloalkylsulfonylalkyl, haloalkylsulfonyl, azidoalkyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, arylthio, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, aryloxy, heterocycloalkylcarbonyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, aminocarbonyl, alkylaminocarbonylalkyl, aralkylthio, heteroarylalcoxyalkyl, heteroaryloxyalkyl, aralkoxy, heteroarylthioalkyl, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl, wherein the aryl and heteroaryl radicals are optionally substitued at a substitutable position with one or more radicals selected from halo, alkylthio, alkylsufinyl, alkyl, cyano, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl and haloalkoxy; wherein R7 is a radical selected from alkyl and amino; and wherein R8 is one or more radicals selected from hydrido, halo, alkyl, haloalkyl, alkoxy, amino, haloalkoxy, cyano, carboxyl, hydroxyl, hydroxyalkyl, alkoxyalkyl, alkylamino, nitro and alkylthio.

公开(公告)号：EP1077971A1

公开(公告)日：2001-02-28

申请号：EP99921363.0

申请日：1999-05-12

申请人： G.D. SEARLE & CO.

发明人： WEIER, Richard, M. ,  COLLINS, Paul, W. ,  XU, Xiangdong ,  CRICH, Joyce, Z. ,  RAO, Shashidhar, N.

IPC分类号： C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  A61K31/44 ,  A61K31/505

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D403/04

摘要： The present invention contemplates 1,5-diaryl-substituted pyrazole compounds which correspond in structure to Formula (I), or a pharmaceutically-acceptable salt thereof: wherein A is =N- or =CH-; and which inter alia, inhibit the activity of p38 MAP kinase. Also contemplated by the invention are processes for the preparation of the contemplated compounds and for the use of a contemplated compound in treating a mammalian host having a p38 kinase- or TNF-mediated disease.

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：EP0809636A1

公开(公告)日：1997-12-03

申请号：EP96904614.0

申请日：1996-02-12

申请人： G.D. SEARLE & CO.

发明人： TALLEY, John, J. ,  BROWN, David, L. ,  NAGARAJAN, Srinivasan ,  CARTER, Jeffery, S. ,  WEIER, Richard, M. ,  STEALEY, Michael, A. ,  COLLINS, Paul, W. ,  SEIBERT, Karen ,  GRANETO, Matthew, J. ,  XU, Xiangdong ,  PARTIS, Richard

IPC分类号： A61K31 ,  A61P1 ,  A61P3 ,  A61P7 ,  A61P9 ,  A61P11 ,  A61P13 ,  A61P17 ,  A61P19 ,  A61P21 ,  A61P25 ,  A61P27 ,  A61P29 ,  A61P31 ,  A61P35 ,  A61P37 ,  A61P43 ,  C07D261 ,  C07D413

CPC分类号： C07D261/10 ,  C07D261/08 ,  C07D261/12 ,  C07D261/18 ,  C07D413/04

摘要： A class of substituted isoxazolyl compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula (III) whrein R7 is selected from hydroxyl, lower alkyl, carboxyl, halo, lower carboxyalkyl, lower alkoxycarbonylalkyl, lower alkoxyalkyl, lower carboxyalkoxyalkyl, lower haloalkyl, lower haloalkylsulfonyloxy, lower hydroxylalkyl, lower aryl (hydroxylalkyl), lower carboxyaryloxyalkyl, lower alkoxycarbonylaryloxyalkyl, lower cycloalkyl, lower cycloalkylalkyl, and lower aralkyl; and wherein R8 is one or more radicals independently selected from hydrido, lower alkylsulfinyl, lower alkyl, cyano, carboxyl, lower alkoxycarbonyl, lower haloalkyl, hydroxyl, lower hydroxyalkyl, lower haloalkoxy, amino, lower alkylamino, lower arylamino, lower aminoalkyl, nitro, halo, lower alkoxy, aminosulfonyl, and lower alkylthio; or a pharmaceutically-acceptable salt thereof.

公开(公告)号：EP0772601B1

公开(公告)日：2002-09-18

申请号：EP95929327.5

申请日：1995-07-27

申请人： G.D. SEARLE & CO.

发明人： WEIER, Richard, M. ,  COLLINS, Paul, W. ,  STEALEY, Michael, A. ,  BARTA, Thomas E., Apartment 3-W ,  HUFF, Renee, M.

IPC分类号： C07D233/54 ,  A61K31/415 ,  C07D233/84 ,  C07D401/04 ,  C07D401/12 ,  C07D405/04 ,  C07D409/04

CPC分类号： C07D233/64 ,  C07D233/84 ,  C07D401/04 ,  C07D401/12 ,  C07D405/04 ,  C07D409/04

摘要： A class of compounds is described for treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by formula (I), wherein R1 is selected from lower alkyl, lower haloalkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower alkenyloxyalkyl, mercapto, lower alkylcarbonyl, lower haloalkylcarbonyl, phenylcarbonyl, lower aralkylcarbonyl, lower aralkenyl, lower aryloxyalkyl, lower aralkyloxyalkyl, lower arylsulfonyl, lower aralkylsulfonyl, lower arylthioalkyl, lower heteroarylalkylthioalkyl, and heteroaryl selected from 2-thienyl, 2-furyl, 3-furyl, 2-pyridyl, 4-pyridyl and 2-benzofuryl; wherein R?2 and R3¿ are independently selected from heteroaryl, cycloalkyl and aryl, wherein the heteroaryl, cycloalkyl and aryl radicals are substituted at a substitutable position with one or more radicals selected from hydrido, halo, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, aminosulfonyl, lower alkyl, cyano, carboxyl, lower alkoxycarbonyl, lower haloalkyl, hydroxyl, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, lower haloalkoxy, amino, lower alkylamino, phenylamino and nitro; and wherein R4 is selected from hydrido, lower alkyl and acyl; or a pharmaceutically acceptable salt thereof.

公开(公告)号：EP0772600B1

公开(公告)日：2002-09-18

申请号：EP95928164.3

申请日：1995-07-27

申请人： G.D. SEARLE & CO.

发明人： KHANNA, Ish, K. ,  WEIER, Richard, M. ,  COLLINS, Paul, W. ,  YU, Yi ,  XU, Xiangdong ,  HUFF, Renee, M. ,  PARTIS, Richard, A. ,  KOSZYK, Francis, J.

IPC分类号： C07D233/54 ,  A61K31/415 ,  C07D233/32 ,  C07D233/90 ,  C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04 ,  C07D417/04

CPC分类号： C07D233/64 ,  C07D233/32 ,  C07D233/90 ,  C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04 ,  C07D419/04

摘要： A class of imidazolyl compounds is described for use in treating inflammation. Compounds of particular interest are defined by formula (II), wherein R3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, acyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkyloxy, cycloalkyloxyalkyle, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cyanoalkyl, cycloalkylsulfonylalkyl, haloalkylsulfonyl, azidoalkyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, arylthio, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, aryloxy, heterocycloalkylcarbonyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, aminocarbonyl, alkylaminocarbonylalkyl, aralkylthio, heteroarylalcoxyalkyl, heteroaryloxyalkyl, aralkoxy, heteroarylthioalkyl, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl, wherein the aryl and heteroaryl radicals are optionally substitued at a substitutable position with one or more radicals selected from halo, alkylthio, alkylsufinyl, alkyl, cyano, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl and haloalkoxy; wherein R7 is a radical selected from alkyl and amino; and wherein R8 is one or more radicals selected from hydrido, halo, alkyl, haloalkyl, alkoxy, amino, haloalkoxy, cyano, carboxyl, hydroxyl, hydroxyalkyl, alkoxyalkyl, alkylamino, nitro and alkylthio.

公开(公告)号：EP0679157A1

公开(公告)日：1995-11-02

申请号：EP94906625.0

申请日：1994-01-14

申请人： G.D. SEARLE & CO. ,  THE MONSANTO COMPANY

发明人： BERTENSHAW, Stephen, R. ,  COLLINS, Paul, W. ,  PENNING, Thomas, D. ,  REITZ, David, B. ,  ROGERS, Roland, S.

IPC分类号： C07D333 ,  A61K31 ,  A61P19 ,  A61P29 ,  A61P43 ,  C07C311 ,  C07C317 ,  C07D207 ,  C07D213 ,  C07D307 ,  C07D401 ,  C07D403 ,  C07D405 ,  C07D409 ,  C07D413 ,  C07D417 ,  C07D471 ,  C07D487

CPC分类号： C07D409/04 ,  A61K31/341 ,  A61K31/365 ,  C07D307/38 ,  C07D307/58 ,  C07D333/16 ,  C07D333/18 ,  C07D333/28 ,  C07D333/38

摘要： A class of 3,4-diaryl substitued thiophene, furan and pyrrole derivatives and analogs thereof, pharmaceutical compositions containing them and methods of using them to treat inflammation and inflammation-related disorders. Compounds of particular interest are defined by formula (I), wherein Y is selected from O, S and NR1; wherein R1 is selected from hydrido and lower alkyl; wherein X is one or two substituent selected from hydrido, halo, lower alkoxycarbonyl and carboxyl; wherein R?2 and R3¿ are independently aryl or heteroaryl; and wherein R?2 and R3¿ are optionally substituted at a substitutable position with one or more radicals selected from sulfamyl, alkylsulfonyl, halo, lower alkoxy and lower alkyl; or a pharmaceutically-acceptable salt thereof.

公开(公告)号：EP0880504B1

公开(公告)日：2003-04-02

申请号：EP97901952.8

申请日：1997-01-24

申请人： G.D. SEARLE & CO.

发明人： KHANNA, Ish, K. ,  WEIER, Richard, M. ,  COLLINS, Paul, W. ,  YU, Ui ,  XU, Xiangdong ,  PARTIS, Richard, A. ,  KOSZYK, Francis, J. ,  HUFF, Renee, M.

IPC分类号： C07D233/54 ,  A61K31/415 ,  C07D233/32 ,  C07D233/90 ,  C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04

CPC分类号： C07D233/64 ,  C07D233/32 ,  C07D233/90 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04

摘要： A class of imidazolyl compounds is described for use in treating inflammation. Compounds of particular interest are defined by formula (V), wherein R3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, heteroaralkyl, acyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heterocyclocarbonyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy, aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl; wherein R4 is a radical selected from hydrido, alkyl and halo; and wherein R?13 and R14¿ are independently selected from aryl and heterocyclo, wherein R?13 and R14¿ are optionally substituted at a substitutable position with one or more radicals independently selected from alkylsulfonyl, aminosulfonyl, halo, alkylthio, alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino and nitro; provided at least one of R?13 and R14¿ is aryl substituted with alkylsulfonyl or aminosulfonyl; or a pharmaceutically-acceptable salt thereof.

公开(公告)号：EP0880504A1

公开(公告)日：1998-12-02

申请号：EP97901952.0

申请日：1997-01-24

申请人： G.D. SEARLE & CO.

发明人： KHANNA, Ish, K. ,  WEIER, Richard, M. ,  COLLINS, Paul, W. ,  YU, Ui ,  XU, Xiangdong ,  PARTIS, Richard, A. ,  KOSZYK, Francis, J. ,  HUFF, Renee, M.

IPC分类号： A61K31 ,  A61P29 ,  C07D233 ,  C07D401 ,  C07D403 ,  C07D405 ,  C07D409 ,  C07D413 ,  C07D417

CPC分类号： C07D233/64 ,  C07D233/32 ,  C07D233/90 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04

摘要： A class of imidazolyl compounds is described for use in treating inflammation. Compounds of particular interest are defined by formula (V), wherein R3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, heteroaralkyl, acyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heterocyclocarbonyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy, aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl; wherein R4 is a radical selected from hydrido, alkyl and halo; and wherein R?13 and R14¿ are independently selected from aryl and heterocyclo, wherein R?13 and R14¿ are optionally substituted at a substitutable position with one or more radicals independently selected from alkylsulfonyl, aminosulfonyl, halo, alkylthio, alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino and nitro; provided at least one of R?13 and R14¿ is aryl substituted with alkylsulfonyl or aminosulfonyl; or a pharmaceutically-acceptable salt thereof.

公开(公告)号：EP0772606A1

公开(公告)日：1997-05-14

申请号：EP95928145.0

申请日：1995-07-26

申请人： G.D. SEARLE & CO.

发明人： TALLEY, John, J. ,  CARTER, Jeffery, S. ,  COLLINS, Paul, W. ,  KRAMER, Steven, W. ,  PENNING, Thomas, D. ,  ROGIER, Donald, J., Jr. ,  ROGERS, Roland, S.

IPC分类号： C07D277 ,  A61K31 ,  A61P3 ,  A61P29 ,  C07D417

CPC分类号： C07D417/04 ,  C07D277/26 ,  C07D277/30 ,  C07D277/42 ,  C07D277/56 ,  C07D417/12

摘要： A class of substituted thiazolyl compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula (II), wherein R4 is selected from alkyl and amino, wherein R5 is selected from aryl, cycloalkyl, cycloalkenyl and heterocyclic; wherein R5 is optionally substituted at a substitutable position with one or more radicals selected from halo, alkylthio, alkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, aminosulfonyl, alkyl, alkenyl, alkynyl, cyano, carboxyl, carboxyalkyl, alkoxycarbonyl, aminocarbonyl, acyl, N-alkylaminocarbonyl, N-arylaminocarbonyl, N,N-dialkylaminocarbonyl, N-alkyl-N-arylaminocarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, haloalkoxy, amino, N-alkylamino, N,N-dialkylamino, heterocyclic and nitro; and wherein R6 is selected from halo, amino, alkoxy, nitro, hydroxyl, aminocarbonyl, acyl, alkylaminocarbonyl, arylaminocarbonyl, alkenyl, alkynyl, haloalkoxy, alkylamino, arylamino, aralkylamino, alkoxycarbonylalkyl, alkylaminoalkyl, heterocycloalkyl, aralkyl, cyanoalkyl, N-alkylsulfonylamino, heteroarylsulfonylalkyl, heteroarylsulfonylhaloalkyl, aryloxyalkyl, aralkyloxyalkyl, aryl and heterocyclo, wherein the aryl and heterocyclo radicals are optionally substituted at a substitutable position with one or more radicals selected from halo, alkyl, alkoxy, alkylthio, alkylsulfinyl, haloalkyl, haloalkoxy, carboxyalkyl, alkoxycarbonyl, aminocarbonyl, amino, acyl and alkylamino; or a pharmaceutically-acceptable salt thereof.