公开(公告)号：WO0027832A2

公开(公告)日：2000-05-18

申请号：PCT/EP9908477

申请日：1999-11-09

Applicant: GLAXO GROUP LTD ,  COLLINS JON LOREN ,  HOLMES CHRISTOPHER PATRICK ,  LENHARD JAMES MARTIN ,  WILLSON TIMOTHY MARK

Inventor： COLLINS JON LOREN ,  HOLMES CHRISTOPHER PATRICK ,  LENHARD JAMES MARTIN ,  WILLSON TIMOTHY MARK

IPC: A61K31/425 ,  A61K31/426 ,  A61K31/427 ,  A61K31/443 ,  A61K31/4439 ,  A61P3/00 ,  A61P3/04 ,  A61P3/10 ,  A61P9/00 ,  A61P19/10 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07D277/14 ,  C07D417/06 ,  C07D417/10 ,  C07D417/12 ,  G01N33/566

CPC classification number: A61K31/4439 ,  A61K31/426 ,  A61K31/443 ,  C07D277/14 ,  G01N33/566 ,  G01N2333/70567

Abstract: The present invention discloses novel PPARgamma ligands of Formula (I) and pharmaceutically acceptable salts and solvates thereof. The present invention also discloses a method for treating osteoporosis by administration of a PPARgamma antagonist.

Abstract translation: 本发明公开了式（I）的新型PPARγ配体及其药学上可接受的盐和溶剂化物。 本发明还公开了一种通过施用PPARγ拮抗剂治疗骨质疏松症的方法。

公开(公告)号：WO2004009091A1

公开(公告)日：2004-01-29

申请号：PCT/US2003/016016

申请日：2003-05-20

Applicant: GLAXO GROUP LIMITED ,  BOGGS, Sharon ,  COLLINS, Jon, L ,  FIVUSH, Adam ,  STEWART, Eugene, Lee ,  WILLSON, Timothy, Mark

Inventor： BOGGS, Sharon ,  COLLINS, Jon, L ,  FIVUSH, Adam ,  STEWART, Eugene, Lee ,  WILLSON, Timothy, Mark

IPC: A61K31/52

CPC classification number: A61K31/522 ,  A61K31/52 ,  A61K31/675 ,  C07D473/04 ,  C07D473/06

Abstract: The invention relates to methods for the treatment or prevention of an LXR mediated disease or condition, including cariovascular disease and atherosclerosis, novel compounds for use in such methods and pharmaceutical compositions comprising compounds for use in such methods.

Abstract translation: 本发明涉及用于治疗或预防LXR介导的疾病或病症的方法，包括心血管疾病和动脉粥样硬化，用于此类方法的新化合物和用于此类方法的化合物的药物组合物。

公开(公告)号：WO02070011A3

公开(公告)日：2003-04-24

申请号：PCT/US0203017

申请日：2002-01-31

Applicant: SMITHKLINE BEECHAM CORP ,  WILLSON TIMOTHY MARK

Inventor： WILLSON TIMOTHY MARK

IPC: A61K38/17 ,  A61P3/04 ,  A61P3/06 ,  A61P3/10 ,  A61P9/00 ,  G01N33/566 ,  A61K31/421 ,  A61K31/426

CPC classification number: G01N33/566 ,  A61K38/1783 ,  G01N2333/70567 ,  G01N2500/00

Abstract: This invention provides a method for identifying a treatment regime for a compound or composition effective in treating a PPAR mediated disease or condition. The method includes determingin a treatment regime for the compound or composition that causes expression of a surrogate market for PPAR delta activity whereby the determined dose and route of administration identifies an effective treatment protocol.

Abstract translation: 本发明提供了一种用于鉴定治疗PPAR介导的疾病或病症的化合物或组合物的治疗方案的方法。 该方法包括确定化合物或组合物的治疗方案，其导致PPARδ活性的替代市场的表达，由此所确定的给药剂量和给药途径识别有效的治疗方案。

公开(公告)号：WO2002061089A2

公开(公告)日：2002-08-08

申请号：PCT/US2002/002992

申请日：2002-01-31

Applicant: SMITHKLINE BEECHAM CORPORATION ,  DAVIS, Roderick, Gerald ,  JOHNSON, Robert, Lloyd, Jr. ,  MILLER, Aaron, Bayne ,  MILLER, Ann, Brier ,  WAY, James, M. ,  WILLIAMS, Shawn, P. ,  WILLSON, Timothy, Mark ,  WISELY, George, Bruce

Inventor： DAVIS, Roderick, Gerald ,  JOHNSON, Robert, Lloyd, Jr. ,  MILLER, Aaron, Bayne ,  MILLER, Ann, Brier ,  WAY, James, M. ,  WILLIAMS, Shawn, P. ,  WILLSON, Timothy, Mark ,  WISELY, George, Bruce

IPC: C12N15/12

CPC classification number: C07K14/4702 ,  C07K2299/00

Abstract: A solved three-dimensional crystal structure of an HNF4g ligand binding domain polypeptide is disclosed, along with a crystal form of the HNF4g ligand binding domain. Methods of designing modulators of the biological activity of HNF4g, and other HNF4 ligand binding domain polypeptides are also disclosed

Abstract translation: 公开了HNF4g配体结合结构域多肽的解决的三维晶体结构以及HNF4g配体结合结构域的晶体形式。 还公开了设计HNF4g和其他HNF4配体结合域多肽的生物学活性调节剂的方法

公开(公告)号：WO1997031907A1

公开(公告)日：1997-09-04

申请号：PCT/EP1997000916

申请日：1997-02-26

Applicant: GLAXO GROUP LIMITED ,  WILLSON, Timothy, Mark ,  MOOK, Robert, Anthony, Jr. ,  KALDOR, Istvan ,  HENKE, Brad, Richard ,  DEATON, David, Norman ,  COLLINS, Jon, Loren ,  COBB, Jeffrey, Edmond ,  BRACKEEN, Markus ,  SHARP, Matthew, Jude ,  O'CALLAGHAN, John, Mark ,  ERICKSON, Greg, Alan ,  BOSWELL, Grady, Evan

Inventor： GLAXO GROUP LIMITED

IPC: C07D263/56

CPC classification number: C07D213/64 ,  A61K31/192 ,  A61K31/216 ,  A61K31/353 ,  A61K31/415 ,  A61K31/4184 ,  A61K31/42 ,  A61K31/422 ,  A61K31/423 ,  A61K31/425 ,  A61K31/427 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4439 ,  A61K31/4453 ,  A61K31/454 ,  A61K31/495 ,  C07C229/36 ,  C07C229/56 ,  C07C237/40 ,  C07C255/54 ,  C07C323/12 ,  C07C2601/14 ,  C07C2601/16 ,  C07D207/08 ,  C07D213/65 ,  C07D213/70 ,  C07D213/74 ,  C07D231/12 ,  C07D233/64 ,  C07D235/12 ,  C07D237/14 ,  C07D249/08 ,  C07D261/08 ,  C07D263/32 ,  C07D263/56 ,  C07D277/24 ,  C07D277/42 ,  C07D311/22 ,  C07D333/36 ,  C07D401/04 ,  C07D405/04 ,  C07D413/04 ,  C07D413/12 ,  C07D417/04

Abstract: A compound having formula (I), wherein A is selected from the group consisting of: (i) phenyl, wherein said phenyl is optionally substituted by one or more halogen atoms, C1-6alkyl, C1-3alkoxy, C1-3fluoroalkoxy, nitrile, or -NR R where R and R are independently hydrogen or C1-3alkyl; (ii) a 5- or 6-membered heterocyclic group containing at least one heteroatom selected from oxygen, nitrogen and sulfur; and (iii) a fused bicyclic ring (a), wherein ring C represents a heterocyclic group as defined in point (ii) above, which bicyclic ring is attached to group B via a ring atom of ring C; B is selected from the group consisting of: (iv) C1-6alkylene; (v) -MC1-6alkylene or C1-6alkyleneMC1-6alkylene, wherein M is O, S, or -NR wherein R represents hydrogen or C1-3 alkyl; (vi) a 5- or 6-membered heterocyclic group containing at least one nitrogen heteroatom and optionally at least one further heteroatom selected from oxygen, nitrogen and sulfur and optionally substituted by C1-3 alkyl; and (vii) Het-C1-6alkylene, wherein Het represents a heterocyclic group as defined in point (vi) above; Alk represents C1-3alkylene; R represents hydrogen or C1-3alkyl; Z is selected from the group consisting of: (viii) -(C1-3alkylene) phenyl, which phenyl is optionally substituted by one or more halogen atoms; and (ix) -NR R , wherein R represents hydrogen or C1-3alkyl, and R represents -Y-(C=O)-T-R , or -Y-(CH(OH))-T-R .

Abstract translation: 具有式（I）的化合物，其中A选自：（i）苯基，其中所述苯基任选被一个或多个卤素原子取代，C 1-6烷基，C 1-3烷氧基，C 1-3氟烷氧基，腈， 或-NR 7 R 8，其中R 7和R 8独立地是氢或C 1-3烷基; （ii）含有至少一个选自氧，氮和硫的杂原子的5-或6-元杂环基; 和（iii）稠合双环（a），其中环C表示如上述点（ii）中所定义的杂环基，该双环通过环C的环原子连接至基团B; B选自：（iv）C 1-6亚烷基; （v）-MC1-6亚烷基或C 1-6亚烷基亚甲基亚烷基，其中M是O，S或-NR 2，其中R 2表示氢或C 1-3烷基; （vi）含有至少一个氮杂原子和任选至少一个选自氧，氮和硫的另外的杂原子并任选被C 1-3烷基取代的5-或6-元杂环基; 和（vii）Het-C 1-6亚烷基，其中Het表示如上述（vi）中所定义的杂环基; Alk表示C1-3亚烷基; R 1表示氢或C 1-3烷基; Z选自：（ii） - （C 1-3亚烷基）苯基，该苯基任选被一个或多个卤素原子取代; 和（ix）-NR 3 R 4，其中R 3表示氢或C 1-3烷基，R 4表示-Y-（C = O）-TR 5或-Y- （CH（OH）） - TR <5>。

公开(公告)号：WO2003090745A1

公开(公告)日：2003-11-06

申请号：PCT/US2003/010519

申请日：2003-04-07

Applicant: SMITHKLINE BEECHAM CORPORATION ,  KLIEWER, Steven, Anthony ,  WILLSON, Timothy, Mark

Inventor： KLIEWER, Steven, Anthony ,  WILLSON, Timothy, Mark

IPC: A61K31/42

CPC classification number: A61K31/4439 ,  A61K31/42

Abstract: Methods for the treatment of cholestatic liver disease and reduction and prevention of hepatic injury resulting from cholestasis via administration of a FXR ligand are provided.

Abstract translation: 提供了通过施用FXR配体治疗胆汁淤积性肝病和减少和预防胆汁淤积引起的肝损伤的方法。

公开(公告)号：WO02061089A3

公开(公告)日：2003-10-16

申请号：PCT/US0202992

申请日：2002-01-31

Applicant: SMITHKLINE BEECHAM CORP ,  DAVIS RODERICK GERALD ,  JOHNSON ROBERT LLOYD JR ,  MILLER AARON BAYNE ,  MILLER ANN BRIER ,  WAY JAMES M ,  WILLIAMS SHAWN P ,  WILLSON TIMOTHY MARK ,  WISELY GEORGE BRUCE

Inventor： DAVIS RODERICK GERALD ,  JOHNSON ROBERT LLOYD JR ,  MILLER AARON BAYNE ,  MILLER ANN BRIER ,  WAY JAMES M ,  WILLIAMS SHAWN P ,  WILLSON TIMOTHY MARK ,  WISELY GEORGE BRUCE

IPC: C07K14/47 ,  C07K14/72 ,  C12N15/12 ,  G01N33/48 ,  G01N33/50 ,  G06F19/00 ,  G01N33/68

CPC classification number: C07K14/4702 ,  C07K2299/00

Abstract: A solved three-dimensional crystal structure of an HNF4g ligand binding domain polypeptide is disclosed, along with a crystal form of the HNF4g ligand binding domain. Methods of designing modulators of the biological activity of HNF4g, and other HNF4 ligand binding domain polypeptides are also disclosed

Abstract translation: 公开了HNF4g配体结合结构域多肽的解决的三维晶体结构以及HNF4g配体结合结构域的晶体形式。 还公开了设计HNF4g和其他HNF4配体结合域多肽的生物学活性调节剂的方法

公开(公告)号：WO1997036579A1

公开(公告)日：1997-10-09

申请号：PCT/EP1997001552

申请日：1997-03-27

Applicant: GLAXO GROUP LIMITED ,  WILLSON, Timothy, Mark

Inventor： GLAXO GROUP LIMITED

IPC: A61K31/00

CPC classification number: A61K31/196 ,  A61K31/00 ,  Y10S514/909

Abstract: The use of agonists of the peroxisome proliferator activated receptor alpha (PPAR alpha ) for the manufacture of a medicament for the treatment of obesity and methods of treating obesity comprising the administration of a therapeutic amount of a PPAR alpha agonist.

Abstract translation: 使用过氧化物酶体增殖物激活受体α（PPARα）的激动剂用于制备治疗肥胖症的药物和治疗肥胖症的方法，包括施用治疗量的PPARα激动剂。

公开(公告)号：WO1996011940A1

公开(公告)日：1996-04-25

申请号：PCT/EP1995004026

申请日：1995-10-12

Applicant: GLAXO WELLCOME INC. ,  DEZUBE, Milana ,  HIRST, Gavin, Charles ,  WILLSON, Timothy, Mark ,  SHERRILL, Ronald, George ,  SUGG, Elizabeth, Ellen ,  SZEWCZYK, Jerzy, Ryszard

Inventor： GLAXO WELLCOME INC.

IPC: C07K05/062

CPC classification number: C07D223/16 ,  A61K38/00 ,  C07D243/14 ,  C07D403/06 ,  C07D403/12 ,  C07K5/0222 ,  C07K5/06026 ,  C07K5/06078 ,  C07K5/06104 ,  C07K5/06139 ,  C07K5/06191 ,  C07K5/0821

Abstract: A CCK-A agonist of the general formula (I) R R NCOCH2N(R )COR and physiologically acceptable salts thereof wherein, R is independently C3-6alkyl, C3-6cycloalkyl, C3-6alkenyl, phenyl, -(CH2)pCN or -(CH2)pCOO(C1-4alkyl) and R is independently C3-6alkyl, C3-6cycloalkyl, C3-6alkenyl, benzyl, phenyl or phenyl mono- or disubstituted independently with C1-3alkyl, cyano, hydroxy, dimethylamino, -O(C1-4alkyl), -O(CH2C6H5), -NH(C1-4alkyl), -COO(C1-4alkyl), -N(C1-4alkyl)2 pyrrolidino, morpholino, halogen or C1-3alkyl substituted by one or more fluorine atoms or R is C1-2alkyl and R is phenyl substituted at the 2- or 4-position with chloro, methyl, methoxy or methoxycarbonyl; or R and R together with the nitrogen atom to which they are attached represent the group of formula (II), wherein R is hydrogen or methyl, R represents hydrogen, hydroxy, fluoro dimethylamino, C1-4alkoxy or benzyloxy, and m is zero, 1 or 2; R represents a group selected from C1-6alkyl; phenyl or phenyl substituted by one or two groups independently selected from C1-3alkyl, C1-4alkoxy or halogen; or thiophenyl; R is a group of formula (III) or (IV).

Abstract translation: 通式（I）R 1 R 2 NCOCH 2 N（R 3）COR 4的CCK-A激动剂及其生理学上可接受的盐，其中R 1独立地为C 3-6烷基， C 1-6烯基，苯基， - （CH 2）pCN或 - （CH 2）p COO（C 1-4烷基）和R 2独立地是C 3-6烷基，C 3-6环烷基，C 3-6烯基，苄基， 氰基，羟基，二甲基氨基，-O（C 1-4烷基）， - O（CH 2 C 6 H 5），-NH（C 1-4烷基），-COO（C 1-4烷基）， - N（C 1-4烷基） ）2吡咯烷子基，吗啉代，卤素或被一个或多个氟原子取代的C 1-3烷基或R 1是C 1-2烷基，R 2是在2-或4-位被氯，甲基，甲氧基或 甲氧羰基; 或R 1和R 2与它们所连接的氮原子一起代表式（II）的基团，其中R 7是氢或甲基，R 8表示氢，羟基，氟二甲基氨基 ，C 1-4烷氧基或苄氧基，m为0,1或2; R 3表示选自C 1-6烷基的基团; 苯基或被一个或两个独立地选自C 1-3烷基，C 1-4烷氧基或卤素的基团取代的苯基; 或噻吩基; R 4是式（III）或（IV）的基团。

公开(公告)号：WO2004009091A8

公开(公告)日：2004-12-29

申请号：PCT/US0316016

申请日：2003-05-20

Applicant: GLAXO GROUP LTD ,  BOGGS SHARON ,  COLLINS JON L ,  FIVUSH ADAM ,  STEWART EUGENE LEE ,  WILLSON TIMOTHY MARK

Inventor： BOGGS SHARON ,  COLLINS JON L ,  FIVUSH ADAM ,  STEWART EUGENE LEE ,  WILLSON TIMOTHY MARK

IPC: C07D473/06 ,  A61K31/52 ,  A61K31/522 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/55 ,  A61P3/06 ,  A61P9/00 ,  A61P9/10 ,  A61P43/00 ,  C07D473/04 ,  C07D473/08 ,  C07D273/04

CPC classification number: A61K31/522 ,  A61K31/52 ,  A61K31/675 ,  C07D473/04 ,  C07D473/06

Abstract: The invention relates to methods for the treatment or prevention of an LXR mediated disease or condition, including cariovascular disease and atherosclerosis, novel compounds for use in such methods and pharmaceutical compositions comprising compounds for use in such methods.